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En el contexto actual de digitalización, las plataformas basadas en plantillas para la creación de sitios web se han vuelto esenciales, facilitando el rápido desarrollo y mantenimiento de páginas web. El proyecto Genweb, que respalda cerca de 500 sitios web principalmente institucionales de la Universidad Politécnica de Cataluña (UPC), es un claro ejemplo de ello. Dada la magnitud y estructura de Genweb, se identifica la necesidad de una herramienta centralizada, Genweb Manager (GWManager), para administrar eficazmente la información y operaciones relacionadas. Sin embargo, la versión actual de GWManager, basada en Python 2 y con deficiencias en su documentación y funcionamiento, no cumple adecuadamente con este papel. Ante el lanzamiento inminente de Genweb 6, este proyecto final de grado tiene como objetivo desarrollar una versión actualizada de GWManager que aborde sus limitaciones y esté preparada para integrarse con la nueva versión de Genweb. Esta actualización se realizará en colaboración con iThinkUPC S.L., con un enfoque en la robustez, confiabilidad y escalabilidad, garantizando una gestión eficiente y centralizada de la red de sitios web bajo el paraguas de Genweb.

Templates have emerged as an effective approach to simplifying the visualization design and programming process. For example, they enable users to quickly generate multiple visualization designs even when using complex toolkits like D3. However, these templates are often treated as rigid artifacts that respond poorly to changes made outside of the template’s established parameters, limiting user creativity. Preserving the user’s creative flow requires a more dynamic approach to template-based visualization design, where tools can respond gracefully to users’ edits when they modify templates in unexpected ways. In this paper, we leverage the structural similarities revealed by templates to design resilient support features for prototyping D3 visualizations: recommendations to suggest complementary interactions for a users’ D3 program; and code augmentation to implement recommended interactions with a single click, even when users deviate from pre-defined templates. We demonstrate the utility of these features in Mirny, a designfocused prototyping environment for D3. In a user study with 20 D3 users, we find that these automated features enable participants to prototype their design ideas with significantly fewer programming iterations. We also characterize key modification strategies used by participants to customize D3 templates. Informed by our findings and participants’ feedback, we discuss the key implications of the use of templates for interleaving visualization programming and design.

1D metal halide perovskite (MHP) nanowires (NWs) have energized research interest owing to their unique characteristics; they are grain-boundary-free, efficiently transport axial carriers, in conjunction with strong radial spatial confinement. Herein, recent progress in the synthesis, integration, property characterization, and advanced optoelectronic applications of MHP NWs is systematically reviewed. The approaches to synthesize MHP NWs are mainly classified into solution-phase and vapor-phase methods, as well as the top-down technique. Meanwhile, highly ordered patterns/templates-assisted and surface-guided alignment methods are utilized to integrate MHP NWs into NW arrays. The enhanced long-term stability and superior optoelectronic properties of MHP NWs enable excellent optoelectronic device performance, where solar cells, photodetectors, image sensors, bionic eyes, light-emitting diodes, resistive random-access memories, and field-effect transistors are mainly discussed. Finally, some perspectives for further direction of exploration to improve the device performance and path ways toward their practical applications are also provided. © 2022 Wiley-VCH GmbH.

Broad evolutionary expansion of polymerase families has enabled specialization of their activities for distinct cellular roles. In addition to template-complementary synthesis, many polymerases extend their duplex products by nontemplated nucleotide addition (NTA). This activity is exploited for laboratory strategies of cloning and sequencing nucleic acids and could have important biological function, although the latter has been challenging to test without separation-of-function mutations. Several retroelement and retroviral reverse transcriptases (RTs) support NTA and also template jumping, by which the RT performs continuous complementary DNA (cDNA) synthesis using physically separate templates. Previous studies that aimed to dissect the relationship between NTA and template jumping leave open questions about structural requirements for each activity and their interdependence. Here, we characterize the structural requirements for cDNA synthesis, NTA, template jumping, and the unique terminal transferase activity of Bombyx mori R2 non-long terminal repeat retroelement RT. With sequence alignments and structure modeling to guide mutagenesis, we generated enzyme variants across motifs generally conserved or specific to RT subgroups. Enzyme variants had diverse NTA profiles not correlated with other changes in cDNA synthesis activity or template jumping. Using these enzyme variants and panels of activity assay conditions, we show that template jumping requires NTA. However, template jumping by NTA-deficient enzymes can be rescued using primer duplex with a specific length of 3' overhang. Our findings clarify the relationship between NTA and template jumping as well as additional activities of non-long terminal repeat RTs, with implications for the specialization of RT biological functions and laboratory applications.

Monomorphization and dynamic dispatch are two common techniques for implementing polymorphism in statically typed programming languages. Function templates in C++ use the former technique to enable algorithms written as generic functions to be efficiently reused with multiple different data types by producing a separate function instantiation for each invocation that uses a unique permutation of argument types. This avoids the overhead of indirection associated with dynamic dispatch and allows the generated code of each instantiation to be optimized by the compiler for its specific concrete types, which typically yields great improvements in runtime performance over any dynamic approach. The disadvantage of this implementation, compared to the type-erased generics found in many other programming languages, is that careless over-use of templates with many different argument types can lead to an excessive amount of redundant code being generated for the same function. This increase in code size may increase the binary size of the final program and reduce the amount of useful code that can fit into the processor's instruction cache during execution, reducing code locality and thereby potentially reducing performance. Monomorphization can also increase compilation time due to the increase in generated code that needs to be compiled and optimized. This thesis presents a heuristic-based approach to generic programming that allows function templates to be automatically converted to use dynamic dispatch in scenarios where the resulting negative impact on runtime performance is predicted to be low. The thesis project includes the development of a proof of concept plugin for the Clang compiler frontend that can be used to compile existing C++ projects with the conversions applied. The design of a heuristic function for determining whether a given function template should use monomorphization or dynamic dispatch based on statically known metrics is proposed based on the result

Introduction: The Australasian Resuscitation Outcomes Consortium (Aus-ROC) out-of-hospital cardiac arrest (OHCA) Epistry (Epidemiological Registry) now covers 100% of Australia and New Zealand (NZ). This study reports and compares the Utstein demographics, arrest characteristics and outcomes of OHCA patients across our region. Methods: We included all OHCA cases throughout 2019 as submitted to the Epistry by the eight Australian and two NZ emergency medical services (EMS). We calculated crude and age-standardised incidence rates and performed a national and EMS regional comparison. Results: We obtained data for 31,778 OHCA cases for 2019: 26,637 in Australia and 5,141 in NZ. Crude incidence was 107.9 per 100,000 person-years in Australia and 103.2/100,000 in NZ. Overall, the majority of OHCAs occurred in adults (96%), males (66%), private residences (76%), were unwitnessed (63%), of presumed medical aetiology (83%), and had an initial monitored rhythm of asystole (64%). In non-EMS-witnessed cases, 38% received bystander CPR and 2% received public defibrillation. Wide variation was seen between EMS regions for all OHCA demographics, arrest characteristics and outcomes. In patients who received an EMS-attempted resuscitation (13,664/31,778): 28% (range across EMS = 13.1% to 36.7%) had return of spontaneous circulation (ROSC) at hospital arrival and 13% (range across EMS = 9.9% to 20.7%) survived to hospital discharge/30-days. Survival in the Utstein comparator group (bystander-witnessed in shockable rhythm) varied across the EMS regions between 27.4% to 42.0%. Conclusion: OHCA across Australia and NZ has varied incidence, characteristics and survival. Understanding the variation in survival and modifiable predictors is key to informing strategies to improve outcomes.

[Abstract]: The objective of this project is the development of a report generation module in the context of an existing IoT platform. These reports will be composed of widgets and will be generated automatically from templates using the data stored in the platform, in order to extract useful information for the user in their decision making process., [Resumen]: El objetivo de este proyecto es el desarrollo de un módulo de generación de informes en el contexto de una plataforma IoT ya existente. Estos informes estarán compuestos de widgets y se generarán automáticamente a partir de plantillas usando los datos almacenados en la plataforma, para permitir extraer información útil para el usuario en su proceso de toma de decisiones.

Zeolites are essential materials to industry due to their adsorption and catalytic properties. The best current approach to prepare a targeted zeolite still relies on trial and error's synthetic procedures since a rational understanding of the impact of synthesis variables on the final structures is still missing. To discern the role of a variety of organic templates, we perform simulations of the early stages of condensation of silica oligomers by combining DFT, Brønsted-Evans-Polanyi relationships and kinetic Monte Carlo simulations. We investigate an extended reaction path mechanism including 258 equilibrium reactions and 242 chemical species up to silica octamers, comparing the computed concentrations of Si oligomers with 29 SI NMR experimental data. The effect of the templating agent is linked to the modification of the intramolecular H-bond network in the growing oligomer, which produces higher concentration of 4-membered ring intermediates, precursors of the key double-four ring building blocks present on more than 39 known zeolite topologies.

[ES] Los Enterprise Resource Planning (ERP) son herramientas de gran utilidad en el contexto empresarial, dado que permiten a una organización gestionar sus procesos de negocio e información mediante la integración de diferentes aplicaciones, así como automatizar la planificación, gestión y trazabilidad de los recursos. Una de esas aplicaciones o módulos de gran importancia en estos ERPs, sería el de Listados e Informes, que permite extraer información del sistema y presentarla unificadamente para apoyar los procesos de toma de decisiones. Para el diseño de las Plantillas asociadas a estos Listados e Informes, existen los conocidos como Diseñadores de Plantillas. Estos Diseñadores, buscan ofrecer herramientas al diseño de estas Plantillas, de forma que se establezcan partes fijas, comunes para todas las instancias o generaciones de un Listado o Informe dado, y otras variables, que dependerán de los datos de la instancia o generación concreta de dicho Informe o Listado. En el presente documento se expondrán las diferentes mejoras llevadas a cabo sobre un Diseñador de Plantillas en formato WordprocessingML de Listados e Informes, con el objetivo que dichas mejoras sean suficientes para incrementar las funcionalidades y posibilidades de diseño que el Diseñador ya ofrece. Durante el desarrollo del proyecto, se expondrán las diferentes especificaciones de requisitos, decisiones de diseño, problemas encontrados y resultados obtenidos durante y tras la implementación de dichas mejoras., [EN] Enterprise Resource Planning (ERP) are tools that offer great value for businesses, since they allow any organization to manage their business processes and information by the integration of several applications, as well as enabling for the automation of the planning, management, and traceability of resources. One of those applications or modules of great value, is the Report module, which allows for extracting information from the system and presenting it in a way that assists the decision-making process. For designing those Templates associated to Reports, there are the so-called Templates Designers. Those Designers present several features and tools for assisting in the design of those Templates, in a way that there are some fixed parts, common to all the instances or generations of a given Report, and other variable parts, which depend on the data of the instance or generation of this given Reports. In this document we will present several enhancements to a Reports Templates Designer for the WordprocessingML format, so that those enhancements improve the functionality and design possibilities of that same Designer. Through the development of this project, the different requirement specification, design decisions, encountered difficulties and results acquired during and after the implementation of those enhancements will be explained.

Membrane nanotubes (NTs) and their networks play an important role in intracellular membrane transport and intercellular communications. The transport characteristics of the NT lumen resemble those of conventional solid-state nanopores. However, unlike the rigid pores, the soft membrane wall of the NT can be deformed by forces driving the transport through the NT lumen. This intrinsic coupling between the NT geometry and transport properties remains poorly explored. Using synchronized fluorescence microscopy and conductance measurements, we revealed that the NT shape was changed by both electric and hydrostatic forces driving the ionic and solute fluxes through the NT lumen. Far from the shape instability, the strength of the force effect is determined by the lateral membrane tension and is scaled with membrane elasticity so that the NT can be operated as a linear elastic sensor. Near shape instabilities, the transport forces triggered large-scale shape transformations, both stochastic and periodic. The periodic oscillations were coupled to a vesicle passage along the NT axis, resembling peristaltic transport. The oscillations were parametrically controlled by the electric field, making NT a highly nonlinear nanofluidic circuitry element with biological and technological implications.

Reflective practice plays a significant role in effective teaching. However, for pre-service teachers (PSTs), it can be a difficult process to not only think reflectively but to understand its importance in their teaching practice. This research focused on the development of a framework for written reflective practice embedded within professional experience (PEx) units. In tutorials, PSTs were provided with video technology to film themselves performing teaching tasks. A reflective framework provided a structure to assist in reflecting on the teaching task. Dialogical teaching and coaching by tutors as well as peer discussion scaffolded the reflective process. At the end of the semester, PSTs and tutors were invited to complete a survey on the reflective processes they had used. This paper focuses on the development of the reflective framework and the feedback received on the use of the framework as a reflective tool. The findings reveal that the PSTs and most tutors found the format useful in structuring reflective practice. The framework and its repeated use over time has potential to build professional knowledge and skills and sustain ongoing reflective practice into the PSTs professional careers.

Gotland Slagteri AB jointly with pig producers experienced that several construction projects of pig facilities were delayed or hindered due to insufficient locally established advisory services, specifically with competence in construction of pig facilities and the associated growth process. In corporation with the unit of Agriculture and Horticulture at Research Institutes of Sweden (RISE) and the farm advisory service, Gård och Djurhälsan, a project was carried out with the aim to write a handbook about the construction and growth process. One of the objectives with the handbook was to serve as a manual in which a pig producer could get more information about a specific topic relevant in the process. The handbook is composed of shorter texts in addition to checklists, "step by step", templates, forms and calculation tools. The project group has had several, so-called dialogue meetings, where specific topics, relevant to the construction and growth process, have been discussed within the group or with the participation of experts. The purpose of these meetings has been to retrieve deeper knowledge of specific topics, e.g., pig production planning, bank and finances, disease control and organic production. All these dialogue meetings have resulted in various chapters in this handbook. Additionally, there are a stand-alone template about writing a work environment plan for construction sites, several calculation tools for the operational phases in pig production, a template for ventilation and heat demand in pig units, a construction investment calculation tool and a time planning tool, i.e., a Gantt chart. The guidance focuses on the administration of a construction project and the growth process related to it. This guide does not contain topics related to e.g., crop production, feed production or manure handling. Neither such administration as required during the actual operational phase of the pig facility, such as systematic work environment plan or systematic f, Denna vägledning är resultatet av att Gotlands Slagteri AB tillsammans med några av öns grisproducenter upplevde att flera byggnadsinvesteringar på grisgårdar på Gotland försenades eller körde fast på grund av att det inte fanns tillräcklig lokal bygg- och grisrådgivning i samband med en byggprocess. Tillsammans med RISE Jordbruk och trädgård samt Gård och Djurhälsan genomfördes ett projekt som resulterade i denna vägledning. Vägledningen ska fungera som ”en uppslagsbok” där grisproducenten ska kunna läsa om ett specifikt ämne beroende vad som är aktuellt i byggnads- och investeringsskedet. Vägledningen är uppbyggd med textavsnitt och hjälpmedel i form av ”att tänka på-listor”, checklistor, ”steg för steg”, mallar och beräkningsverktyg. I de eventuella delar där grisproducenten fortfarande upplever utmaningar och svårigheter kan vägledningen bidra till en insikt att sakkunniga behöver anlitas. Under projekttiden har projektgruppen haft ett antal ”dialogmöten” där projektgruppen själv, eller genom att andra sakkunniga bjudits in, diskuterat ett specifikt ämne. Syftet med dessa dialogmöten har varit att fånga upp de delar som är viktiga för en grisproducent att beakta i samband med en investering och byggnation av ett grisstall. Ämnena har till exempel rört produktionsplanering, tillstånd från myndigheter, ekonomi, slaktplanering, smittskydd och arbetsmiljö. Dessa dialogmöten har utmynnat i olika kapitel i denna vägledning. Separat från denna vägledning finns även en mall för att skriva en arbetsmiljöplan vid byggnadsarbeten. Dessutom finns beräkningsverktyg och mallar gällande ventilation- och värmebehovsberäkning i grisstallar, investeringskalkyl, tidplaneringsverktyg samt driftkalkyler för smågris- respektive slaktgrisproduktion. Vägledningen fokuserar på administrationen av ett byggprojekt och tillväxtprocessen innan själva byggstarten. Denna vägledning behandlar inte områden såsom växtodling, foderproduktion och spridningsarealer för gödsel utan koncentreras krin, Denna vägledning är resultatet av projektet ”Utökad grisproduktion på Gotland – ett samarbetsprojekt” som finansierats av Landsbygdsprogrammet 2014–2020 och Leader Gute. Projektgruppen har bestått av RISE Jordbruk och trädgård, Gotlands Slagteri AB, Gård och Djurhälsan, lantbrukare Olof Ahlby samt Västerväte Lantbruk AB. Projektledare har Cecilia Hagberg (RISE Jordbruk och trädgård) varit.

Selfish, non-long terminal repeat (non-LTR) retroelements and mobile group II introns encode reverse transcriptases (RTs) that can initiate DNA synthesis without substantial base pairing of primer and template. Biochemical characterization of these enzymes has been limited by recombinant expression challenges, hampering understanding of their properties and the possible exploitation of their properties for research and biotechnology. We investigated the activities of representative RTs using a modified non-LTR RT from Bombyx mori and a group II intron RT from Eubacterium rectale Only the non-LTR RT supported robust and serial template jumping, producing one complementary DNA (cDNA) from several templates each copied end to end. We also discovered an unexpected terminal deoxynucleotidyl transferase activity of the RTs that adds nucleotide(s) of choice to 3' ends of single- and/or double-stranded RNA or DNA. Combining these two types of activity with additional insights about nontemplated nucleotide additions to duplexed cDNA product, we developed a streamlined protocol for fusion of next-generation sequencing adaptors to both cDNA ends in a single RT reaction. When benchmarked using a reference pool of microRNAs (miRNAs), library production by Ordered Two-Template Relay (OTTR) using recombinant non-LTR retroelement RT outperformed all commercially available kits and rivaled the low bias of technically demanding home-brew protocols. We applied OTTR to inventory RNAs purified from extracellular vesicles, identifying miRNAs as well as myriad other noncoding RNAs (ncRNAs) and ncRNA fragments. Our results establish the utility of OTTR for automation-friendly, low-bias, end-to-end RNA sequence inventories of complex ncRNA samples.

The prebiotic synthesis of ribonucleotides is likely to have been accompanied by the synthesis of noncanonical nucleotides including the threo-nucleotide building blocks of TNA. Here, we examine the ability of activated threo-nucleotides to participate in nonenzymatic template-directed polymerization. We find that primer extension by multiple sequential threo-nucleotide monomers is strongly disfavored relative to ribo-nucleotides. Kinetic, NMR and crystallographic studies suggest that this is due in part to the slow formation of the imidazolium-bridged TNA dinucleotide intermediate in primer extension, and in part because of the greater distance between the attacking RNA primer 3'-hydroxyl and the phosphate of the incoming threo-nucleotide intermediate. Even a single activated threo-nucleotide in the presence of an activated downstream RNA oligonucleotide is added to the primer 10-fold more slowly than an activated ribonucleotide. In contrast, a single activated threo-nucleotide at the end of an RNA primer or in an RNA template results in only a modest decrease in the rate of primer extension, consistent with the minor and local structural distortions revealed by crystal structures. Our results are consistent with a model in which heterogeneous primordial oligonucleotides would, through cycles of replication, have given rise to increasingly homogeneous RNA strands.

Stemming from the President’s Management Agenda, the Office of Management and Budget has set goals per functional area to guide the federal government’s modernization. The goal for acquisitions is to be frictionless, or to be able to deliver commercial items at the same speed as the market and non-commercial items by using modern business practices and technologies. The contractor responsibility determination process is an acquisition process that occurs at least once for every contract and, if modernized, would affect the speed at which every contract is awarded. Initial research reveals that the execution of this process is not standardized throughout and within the different federal agencies, lacks compliance, and does not meet the intent of the policy stated in Federal Acquisition Regulation (FAR) 9.1. Using a business process improvement method, the contractor responsibility determination process is dissected to reveal issues. Potential solutions are then discussed to solve these issues. One of these solutions is then prototyped and field-tested. The thesis ends with a discussion of alternative processes and recommendations on those processes that could follow the same analysis and prototype development pattern., Outstanding Thesis, Captain, United States Air Force, Approved for public release. distribution is unlimited

Studentkonsultprojekt gör det möjligt för studenter att applicera sin kunskap i näringslivet samtidigt som det blir mindre kostsamt för företagen att anlita konsulter. Då jobbsökande via internet blir allt vanligare finns det ett behov av en webbapplikation för konsultuppdrag som kopplar samman studenter och företag. En av de viktigaste aspekterna för att skapa en konkurrenskraftig webbapplikation är användbarheten. Således är intentionen med denna studie att undersöka Hur kan en webbapplikation för konsultuppdrag mellan företag och studenter implementeras för att uppfattas som användbar av studenter? För att besvara frågeställningen har en webbapplikation för förmedling av konsulttjänster mellan företag och studenter utvecklats. Webbapplikationen baseras på en teoretisk grund där olika dimensioner av begreppet användbarhet analyserats. De dimensioner som lyfts är effektivitet, ändamålsenlighet och tillfredsställelse. I tillägg till detta har vikten av att specificera användare och de estetiska aspekternas påverkan på användbarhet behandlats. För att utvärdera om webbapplikationen upplevs som användbar testas den på tre testgrupper i tre olika skeden för att undersöka deras upplevelse av webbapplikationen. Testerna utgår från metoden thinking aloud tillsammans med enkäterna System Usability Scale (SUS) och Visual Aesthetics of Websites Inventory Short (VisAWI-S). SUS- och VisAWI-S-enkäterna gav indikationer på en starkt användbar applikation genom hela utvecklingsprocessen. Detta utifrån implementation av en design som främst utgick från principerna enkelhet och färgrikedom samt fokusområdena Synlighet av systemstatus, Igenkänning istället för återkallande, Flexibilitet och effektiv användning och Estetisk och minimalistisk design. Genom att analysera resultaten från thinking aloud-testerna kunde en tydlig minskning av negativa kommentarer identifieras mellan användartest 1-3. Utifrån dessa testresultat, dras slutsatserna att genom återkoppling relaterad till utförd, Studentconsulting makes it possible for students to use their knowledge in business cases. In addition to this it also reduces the cost for enterprises when hiring consultants. As job hunting via the internet becomes more common there is a need for a web application that connects company projects with students who are interested in consulting. One of the most prominent aspects for a web application to be competitive is usability. The intention with this study is to examine How can a webapplication for consulting jobs between enterprises and students be implemented to be perceived as useful by students? To answer this question a web application for intermediation of consulting jobs between enterprises and students has been developed. The web application is developed on a theoretical basis where the different dimensions of the term usability has been analysed. These dimensions are efficiency, effectiveness and satisfaction. In addition to this the importance of specifying users and the aesthetic aspects effects on usability has been discussed. To evaluate if the web aplication is perceived as useful it is tested on three groups of people on three different occasions to examine their perception of the web application. The tests are based on the thinking aloud method together with the questionnaires System Usability Scale (SUS) and Visual Aesthetics of Websites Inventory Short (VisAWI-S). The SUS and VisAWI-S questionnaires indicated that the web application had a high level of usability throughout the development process. This was achieved through implementing a design based on simplicity and colorfulness as well as the principles Visibility of system status, Recognition rather than recall, Flexibility and efficiency of use and Aesthetic and minimalist design. By analysing the results from the thinking aloud tests a reduction in negative comments between test 1 and 3 could be identified. From the test results, the conclusion is that through responses related to complet

Telomerase is unique among the reverse transcriptases in containing a noncoding RNA (known as telomerase RNA (TER)) that includes a short template that is used for the processive synthesis of G-rich telomeric DNA repeats at the 3' ends of most eukaryotic chromosomes1. Telomerase maintains genomic integrity, and its activity or dysregulation are critical determinants of human longevity, stem cell renewal and cancer progression2,3. Previous cryo-electron microscopy structures have established the general architecture, protein components and stoichiometries of Tetrahymena and human telomerase, but our understandings of the details of DNA-protein and RNA-protein interactions and of the mechanisms and recruitment involved remain limited4-6. Here we report cryo-electron microscopy structures of active Tetrahymena telomerase with telomeric DNA at different steps of nucleotide addition. Interactions between telomerase reverse transcriptase (TERT), TER and DNA reveal the structural basis of the determination of the 5' and 3' template boundaries, handling of the template-DNA duplex and separation of the product strand during nucleotide addition. The structure and binding interface between TERT and telomerase protein p50 (a homologue of human TPP17,8) define conserved interactions that are required for telomerase activation and recruitment to telomeres. Telomerase La-related protein p65 remodels several regions of TER, bridging the 5' and 3' ends and the conserved pseudoknot to facilitate assembly of the TERT-TER catalytic core.

The development of aluminum anodization technology features many stages. With the story stretching for almost a century, rather straightforward-from current perspective-technology, raised into an iconic nanofabrication technique. The intrinsic properties of alumina porous structures constitute the vast utility in distinct fields. Nanoporous anodic alumina can be a starting point for: Templates, photonic structures, membranes, drug delivery platforms or nanoparticles, and more. Current state of the art would not be possible without decades of consecutive findings, during which, step by step, the technique was more understood. This review aims at providing an update regarding recent discoveries-improvements in the fabrication technology, a deeper understanding of the process, and a practical application of the material-providing a narrative supported with a proper background.

Lipid membrane nanotubes (NTs) are a widespread template forin vitrostudies of cellular processes happening at high membrane curvature. Traditionally NTs are manufactured one by one, using sophisticated membrane micromanipulations, while simplified methods for controlled batch production of NTs are in growing demand. Here we propose a lab-on-a-chip (LOC) approach to the simultaneous formation of multiple NTs with length and radius controlled by the chip design. The NTs form upon rolling silica microbeads covered by lipid lamellas over the pillars of a polymer micropillar array. The array's design and surface chemistry set the geometry of the resulting free-standing NTs. The integration of the array inside a microfluidic chamber further enables fast and turbulence-free addition of components, such as proteins, to multiple preformed NTs. This LOC approach to NT production is compatible with the use of high power objectives of a fluorescence microscope, making real-time quantification of the different modes of the protein activity in a single experiment possible.

Correct color measurement by contact-type color measuring devices requires that the sample surface fully covers the head of the device, so their use on small samples remains a challenge. Here, we propose to use cardboard adaptors on the two aperture masks (3 and 8 mm diameter measuring area) of a broadly used portable spectrophotometer. Adaptors in black and white to reduce the measuring area by 50% and 70% were applied in this study. Representatives of the family Campanulaceae have been used to test the methodology, given the occurrence of small leaves. Our results show that, following colorimetric criteria, the only setting providing indistinguishable colors according to the perception of the human eye is the use of a 50%-reducing adaptor on the 3-mm aperture. In addition, statistical analysis suggests the use of the white adaptor. Our contribution offers a sound measurement technique to gather ecological information from the color of leaves, petals, and other small samples

Photonic scattering materials, such as biological tissue and white paper, are made of randomly positioned nanoscale inhomogeneities in refractive index that lead to multiple scattering of light. Typically these materials, both naturally occurring or man-made, are formed through self assembly of the scattering inhomogeneities, making it extremely challenging to know the exact positions of these inhomogeneities, let alone control those. Here, the nanofabrication of photonic multiple-scattering media using direct laser writing with a deterministic design is reported on. These deterministic multiple-scattering media consist of submicron-thick polymer nanorods that are randomly oriented within a cubic volume. The total transmission of light is studied as a function of the number of rods and of the sample thickness to extract the scattering and transport mean free paths using radiative transfer theory. Such ability to fabricate photonic multiple-scattering media with deterministic and controllable properties opens up a myriad of opportunities for fundamental studies of light scattering, in particular, in the multiple-scattering regime and with strong anisotropy and for new applications in solid-state lighting and photovoltaics.

Correct color measurement by contact-type color measuring devices requires that the sample surface fully covers the head of the device, so their use on small samples remains a challenge. Here, we propose to use cardboard adaptors on the two aperture masks (3 and 8 mm diameter measuring area) of a broadly used portable spectrophotometer. Adaptors in black and white to reduce the measuring area by 50% and 70% were applied in this study. Representatives of the family Campanulaceae have been used to test the methodology, given the occurrence of small leaves. Our results show that, following colorimetric criteria, the only setting providing indistinguishable colors according to the perception of the human eye is the use of a 50%-reducing adaptor on the 3-mm aperture. In addition, statistical analysis suggests the use of the white adaptor. Our contribution offers a sound measurement technique to gather ecological information from the color of leaves, petals, and other small samples.

The data deluge following the rise of Internet of Things contributes towards the creation of non-reusable data silos. Especially in the environmental sciences domain, syntactic and semantic heterogeneity hinders data re-usability as most times manual labour and domain expertise is required. Both the different syntaxes under which environmental timeseries are formatted and the implicit semantics which are used to describe them contribute to this end. Usually, the real meaning of data is obscured in a combination of short data labels, titles and various value codes, that require domain or institutional knowledge to decipher. The FAIR data principles for scientific data sharing are stewardship offer a framework based on community-adopted metadata. In this work, we present the Environmental Data Acquisition Module (EDAM) which focuses on data interoperability and reuse, and deals with syntactic and semantic heterogeneity using a template approach. Data curators draft templates to describe in an abstract fashion the syntax of the timeseries datasets they want to acquire or disseminate. They complement each template with a metadata file, which is used to annotate observables and their properties (including physical quantities and units of measurement) with terms from an ontology. EDAM employs a reasoner to infer compatibility among syntactically and semantically heterogeneous datasets, and enables timeseries, format and units of measurement transformation on-the-fly. Our approach utilizes a local ontology to store metadata about datasets, which enables EDAM to acquire and transform datasets which were originally stored with different semantics and syntaxes. We demonstrate EDAM in a case study where we transform meteorological input files of four agricultural models. Our approach, allows to cut across environmental data silos and facilitate timeseries reusability, as it enables users to (a) discover datasets in other formats, (b) transform them and (c) reuse them in their

[Resumen] Este proyecto se basa en el análisis, diseño e implementación de un sistema que permita al usuario la gestión de su currículum de manera eficiente y la generación de diferentes instancias del mismo. El modelo con el que se generarán estas instancias será elegido por el usuario cada vez que desee crear un currículum, dentro de los diferentes plantillas ofrecidas por la aplicación. Estas plantillas no solo se diferencian estéticamente sino que cada una se ajustará a un formato de currículum específico. Esto permitirá que el usuario, a través del mismo conjunto de méritos introducidos una única vez en la aplicación, cree un currículum simple o uno que siga formato complejos y específicos como puede ser el currículum para la solicitud de plazas en la UDC. En el desarrollo del proyecto se ha optado por la creación una arquitectura cliente-servidor, empleando para ello tecnologías como Spring o React. Para el almacenamiento de la información se ha empleado un SGBD como PostgreSQL y para el control de versiones se ha utilizado GitLab. El trabajo ha sido gestionado siguiendo una metodología fruto de la adaptación de las mejores prácticas de SCRUM a las peculiaridades del proyecto., [Abstract] This project is based on the analysis, design and implementation of a system that allows the user the management of his curriculum in an efficient way and the generation of different instances of it. The model that will generate those instances will be chosen by the user every time he wants to create a curriculum, within the different templates provided by the application. These templates do not present just aesthetic differences but they would adjust each one to a format of a specific curriculum. This will permit the user, using the same data, the possibility of creating a simple curriculum or more complex formats like the place solicitude curriculum from UDC. In the project development, the choice made was the creation of a client-server architecture, coded in React and Java respectively. The information storage was accomplished using PostgreSQL and the version-control with the help of GitLab. The work was managed using as methodology an adaptation of the SCRUM’s best practices to the peculiarities of the project.

Although traditional three-dimensional (3D) zeolitic-imidazolate framework (ZIF) particles have been explored as promising precursors for preparing carbon-based electrocatalyst for oxygen reduction reaction (ORR), their natural tendency to agglomerate impedes the exposure of the active sites and significantly reduces their ORR performance. Herein, novel Co/Zn-containing bimetallic ZIF nanoleaves are synthesized by the "shape-transforming method in an aqueous system", in which the nitrogen atoms in amines form hydrogen bonds with hydrogen atoms from H2O molecules, which induce the formation of sodalite layers to generate the ZIF nanoleaves. By directly pyrolyzing the ZIF nanoleaves, the obtained cobalt-embedded nitrogen-doped mesoporous carbon (Co-N/C) product possesses refined leaf-like two-dimensional (2D) morphologies. Moreover, the obtained 2D catalyst with a high mass loading of cobalt nanoparticles (31.17 wt%) shows an excellent electrocatalytic performance for the ORR in an alkaline electrolyte. The half-wave potential of the Co-N/C catalyst is 0.825 V versus the reversible hydrogen electrode, which is 14 mV more positive than that of the commercial Pt/C (0.811 V). In addition, the resulting zinc-air battery assembled using the Co-N/C air cathode with a liquid electrolyte exhibits both high open-circuit potential (1.446 V) and high energy density (837.5 W h kgzn-1).

This study is based on the perspective of the Complex Adaptive Systems proposed by THELEN and SMITH (1994). The aim of this paper is to analyze the Child-directed Speech (CDS) (FERGUSON, 1964; CAVALCANTE, 2007) in the phonological development of 1-2 year-old child, acquiring the Brazilian Portuguese (BP) variety of Vitória da Conquista-BA. In order to do so, we investigated the relation between CDS and the emergent templates in the child's speech, such as the phonic patterns that arise for lexical expansion (VIHMAN; CROFT, 2007). After analyzing the data, our initial hypothesis that CDS would play a direct role in the child’s templates was partially confirmed as a strong correspondence between the two types of data was not found, Este estudo, com base na perspectiva dos Sistemas Adaptativos Complexos (THELEN; SMITH, 1994), tem como objetivo analisar a Child-directed Speech (CDS) (FERGUSON, 1964; CAVALCANTE, 2007) no desenvolvimento fonológico de uma criança, de 1 a 2 anos, de Vitória da Conquista-BA, adquirindo o português brasileiro (PB). Para isso, investigamos a relação entre CDS e os templates emergentes na fala da criança, isto é, os padrões fônicos que surgem para expansão lexical (VIHMAN; CROFT, 2007). Após análise dos dados, nossa hipótese inicial de que a CDS desempenharia um papel direto no formato fônico dos templates presentes na fala infantil foi parcialmente confirmada, pois não foi observada uma correspondência forte entre os dois tipos de dados., Este estudio, basado en la perspectiva de los Sistemas Adaptativos Complejos (THELEN; SMITH, 1994), tiene como objetivo analizar el Child-directed Speech (CDS) (FERGUSON, 1964; CAVALCANTE, 2007) en el desarrollo fonológico de un niño, de 1 a 2 años, de Vitória da Conquista-BA, adquiriendo portugués brasileño (PB). Para esto, investigamos la relación entre CDS y templates emergentes en el habla del niño, es decir, los patrones fónicos que surgen para la expansión léxica (VIHMAN; CROFT, 2007). Después del análisis de datos, nuestra hipótesis inicial de que CDS desempeñaría un papel directo en el formato fónico de los templates presentes en el habla infantil se confirmó parcialmente, ya que no hubo una fuerte correspondencia entre los dos tipos de datos.

Environmental timeseries data variety is exploding in the Internet of Things era, making data reuse a very demanding task. Data acquisition and integration remains a laborious step of the environmental data lifecycle. Environmental data heterogeneity is a persistent issue, as data are becoming available through different protocols and stored under diverse, custom formats. In this work, we deal with syntactic heterogeneity in environmental timeseries data. Our approach is based on describing different dataset syntaxes using abstract representations, called templates. We designed and implemented EDAM (Environmental Data Acquisition Module), a template framework that facilitates timeseries data acquisition and integration. EDAM templates are written using programming language-agnostic semantics, and can be reused both for input and output, thus enabling data reuse via transformations across different formats. We demonstrate EDAM generality in seven case studies, which involve scraping online data, extracting observations from a relational database, or aggregating historical timeseries stored in local files. Case studies span different environmental sciences domains, including meteorology, agriculture, urban air quality and hydrology. We also demonstrate EDAM for data dissemination, as instructed by output templates. We identified several syntactic interoperability challenges though the case studies, that include managing with differences in formatting observables, temporal and spatial references, and metadata documentation, and addressed them with EDAM. EDAM implementation has been released under an open-source license.

Diversity-generating retroelements (DGRs) create unparalleled levels of protein sequence variation through mutagenic retrohoming. Sequence information is transferred from an invariant template region (TR), through an RNA intermediate, to a protein-coding variable region. Selective infidelity at adenines during transfer is a hallmark of DGRs from disparate bacteria, archaea, and microbial viruses. We recapitulated selective infidelity in vitro for the prototypical Bordetella bacteriophage DGR. A complex of the DGR reverse transcriptase bRT and pentameric accessory variability determinant (Avd) protein along with DGR RNA were necessary and sufficient for synthesis of template-primed, covalently linked RNA-cDNA molecules, as observed in vivo. We identified RNA-cDNA molecules to be branched and most plausibly linked through 2'-5' phosphodiester bonds. Adenine-mutagenesis was intrinsic to the bRT-Avd complex, which displayed unprecedented promiscuity while reverse transcribing adenines of either DGR or non-DGR RNA templates. In contrast, bRT-Avd processivity was strictly dependent on the template, occurring only for the DGR RNA. This restriction was mainly due to a noncoding segment downstream of TR, which specifically bound Avd and created a privileged site for processive polymerization. Restriction to DGR RNA may protect the host genome from damage. These results define the early steps in a novel pathway for massive sequence diversification.

Biometric recognition systems are widely used to recognize an individual. Fingerprints is a biometric identifier and are today widely used in smartphones for biometric recognition. The fingerprint software used in smartphones are great and fast, and usually implemented for one person usage. A fingerprint software used for smartphones often conducts a one-to-one comparison between the sample and the enrolled templates. Software systems that can be used to recognize a person out of many are desirable. Such a system would conduct one-to-many comparisons. However, using the existing software in smartphones in a product used by many people would be too slow since it has to conduct many one-to-one comparisons between the sample and the enrolled templates. This thesis examines whether it is possible to classify the enrolled templates by K-centroid, such that the number of comparisons in the one-to-many authentication problem is reduced. It was shown that the bag-of-words representation of an image is the best feature to use, together with the cosine similarity, during classification. To further improve the clustering, SVM and balancing were also applied. This combination showed good results and is the most promising method out of all methods examined in this thesis.

Оказываемая фирмой "1С" технологическая поддержка своих программных продуктов имеет большое значение для образовательных учреждений. Актуализация конфигураций "1С" ввиду дискретности и цикличности учебного процесса имеет свою специфику. В статье обсуждается вопрос обновления шаблонов, и предлагаются возможные пути его разрешения.

Metamorphic testing enables the generation of test cases in the absence of an oracle by exploiting relations among different executions of the program under test, called metamorphic relations. In a recent survey, we observed a great variability in the way metamorphic relations are described, typically in an informal manner using natural language. We noticed that the lack of a standard mechanism to describe metamorphic relations often makes them hard to read and understand, which hinders the widespread adoption of the technique. In this paper, we propose a template–based approach for the description of metamorphic relations. The proposed template aims to ease communication among practitioners as well as to contribute to research dissemination. Also, it provides a helpful guide for those approaching metamorphic testing for the first time. For the validation of the approach, we used the proposed template to describe 17 previously published metamorphic relations from different domains and groups of authors, without finding expressiveness problems. We hope that this work eases the diffusion and adoption of metamorphic testing, contributing to the progress of this thriving testing technique.

The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV.

Expansions of short nucleotide repeats produce several neurological and neuromuscular disorders including Huntington disease, muscular dystrophy, and amyotrophic lateral sclerosis. A common pathological feature of these diseases is the accumulation of the repeat-containing transcripts into aberrant foci in the nucleus. RNA foci, as well as the disease symptoms, only manifest above a critical number of nucleotide repeats, but the molecular mechanism governing foci formation above this characteristic threshold remains unresolved. Here we show that repeat expansions create templates for multivalent base-pairing, which causes purified RNA to undergo a sol-gel transition in vitro at a similar critical repeat number as observed in the diseases. In human cells, RNA foci form by phase separation of the repeat-containing RNA and can be dissolved by agents that disrupt RNA gelation in vitro. Analogous to protein aggregation disorders, our results suggest that the sequence-specific gelation of RNAs could be a contributing factor to neurological disease.

This essay presents a philosophical account of musical performance within the tradition of European art music. Although the 19th and 20th century formulation of performance as reproduction has been critiqued in recent scholarly texts, I will argue the case that reproduction—when not exclusively conceived of as the reproduction of the musical work—still provides a useful and accurate characterization of the performance process.The questions that logically follow are “who” and “what” is reproduced? Answering the question of “who,” I will refer to Naomi Cumming’s account of subjectivity as it is maintained in the synthesis of musical signs. Answering the question of “what,” I will diagram the work’s object ontology proposed by Theodor W. Adorno. Having followed these nuanced approaches to the development and maintenance of music’s subjects and objects, I will propose that it would be useful for scholars and musicians to think of templates for musical reproduction. The template concept on the one hand draws attention to the technical and technological nature of performance, the structures of which emerge historically. On the other hand, templates index the subject’s unique cultural position and voice.To this end, the essay will look at three case studies of templates for performance: Fritz Kreisler’s distinctive lilt (deriving from Viennese Ländler and Waltz rhythms), elements of Jascha Heifetz’s bodily formalism (tracking these specifically from some of his teacher, Leopold Auer’s, pedagogical instructions), and Hilary Hahn’s conformity to a metric and sonic consistency as it appears represented in notation.

Metamorphic testing enables the generation of test cases in the absence of an oracle by exploiting relations among different executions of the program under test, called metamorphic relations. In a recent survey, we observed a great variability in the way metamorphic relations are described, typically in an informal manner using natural language. We noticed that the lack of a standard mechanism to describe metamorphic relations often makes them hard to read and understand, which hinders the widespread adoption of the technique. To address this shortcoming, we have proposed a template for the description of metamorphic relations, which aims to ease communication among practitioners as well as contributing to research dissemination. Also, it provides a helpful guide for those approaching metamorphic testing for the first time. This technical report describes the proposed template, records its evolution through its different versions and shows several examples of use.

Chirality is crucial for life. The preparation of enantiopure chiral compounds is highly desirable in the chemical industry, especially in the pharmaceutical sector. In this context, the design of chiral solids able to discriminate between enantiomers of chiral compounds, either during adsorption or asymmetric catalytic processes, is one of the greatest challenges nowadays in chemical research. Zeolite-type materials represent ideal candidates to achieve enantioselective chiral solids since they could combine their high stability, surface area, and shape-selectivity with a potential enantioselectivity that could be enhanced by the confinement effect. Despite the occurrence of chiral zeolite frameworks and the strong interest in preparing these chiral solids, very little success has been met in preparing these in homochiral form. The main strategy to induce chirality in zeolite materials has been the use of chiral structure-directing agents, in an attempt to transfer their chiral feature into the nascent zeolite structure. However, although many chiral organic species have directed the crystallization of zeolite frameworks, some of them even being chiral, there is only one unique very recent example of success in transferring the chirality from the organic structure-directing agent into an enantioenriched chiral zeolite material. Chiral coordination compounds have been very successful in transferring their chirality onto inorganic frameworks through the development of extensive H-bond host–guest interactions, but these chiral materials usually collapse upon removal of the guest species. In this chapter we report the different types of chiral molecules, both organic and organometallic compounds, used so far as structure-directing agents in an attempt to promote the crystallization of homochiral zeolites; we analyze in detail the possible reasons for the general failure in transferring their chirality, and we propose approaches to prepare known chiral zeolite framework

[EN] Several CeO2 and CuO-CeO2 catalysts were prepared using different methods, i.e., a homogeneous precipitation with urea, a nanocasting route using CMK-3 carbon as a hard template and a sol¿gel process using Poly(methyl methacrylate) (PMMA) polymer as a soft template, and tested in the total oxidation of propane. The catalysts were characterized by a number of physicochemical techniques (XRD, N2 adsorption, TPR, XPS, Raman spectroscopy) showing distinct characteristics. For each series, Cu-Ce-O catalysts with low Cu-loadings (5 wt % CuO) showed the highest activity, higher than those samples either without copper or with high Cu-loading (13 wt % CuO). The incorporation of copper leads to an increase of the concentration of bulk defects but if the Cu-loading is too high the surface area drastically falls. The highest activity in the total oxidation of propane was achieved by Cu-containing ceria catalysts synthesized using a polymer as a template, as this method yields high surface area materials. The surface area and the number of bulk/sub-surface defects of the ceria seem to be the main properties determining the catalytic activity

During the last years, a tremendous progress has been achieved in the application of new zeolite materials in many different sectors through different pioneering innovations in the field of zeolite synthesis. At the very core of the production of these new zeolite materials lies the use of organic species as structure-directing agents (SDA), which has been recognized as the most important factor to determine the zeolite product rendered after the crystallization process. These organic species organize the inorganic zeolitic units and drive the crystallization pathway towards the production of particular zeolite framework types. This structure-direction phenomenon frequently works in combination with several other factors related to the chemical composition of the synthesis gels, mainly use of fluoride, concentration (H2O/T ratio), and presence of different heteroatoms, which are also relevant for the crystallization of particular zeolite materials. Several properties determine the structure-directing effect of these organic species, especially their molecular size and shape, hydrophobicity, rigidity vs flexibility, and hydrothermal stability. The properties of the zeolitic materials synthesized can be tuned up to a certain point through the use of rationally selected organic species with particular physico-chemical features as SDA. In this introductory chapter, we briefly review the history of the use of organic cations as SDAs, and give the fundaments of the different aspects related to this structure-direction phenomenon and factors affecting it, explaining the main properties of SDAs, providing some examples of recent uses and trends of organic SDAs, as well as the host–guest chemistry involved. In addition, we pay particular attention to the use of imidazolium-based organic cations as SDAs because of their current relevance in the synthesis of new zeolite materials.

For many years, Sweden has had a reputation for having a comprehensive and women friendly welfare state. However, as in many other European countries during the past few decades, the organization and governing of welfare has undergone profound changes. Through interviews with social workers and the application of theories of governmentality, this thesis analyzes the expressions and consequences of such current organization and governing. One result is that the introduction of meticulous documentation practices of social workers contact with clients, regulate their interaction and constitute a control over both client and social worker. Another result is that the current organization fragments labor and awards more authority to managers, which functions to produce loyalty to the organization and management, rather than clients. This is expressed in demands not to voice protest, as it is said to create a bad mood. It is also expressed in demands to spend as little as possible on clients; short duration of treatment, preference for outpatient treatment and by making it difficult to receive financial support. This austerity is legitimized through the intermeshing of different ideals; budget awareness, evidence that supports short and outpatient treatment and that clients in order to change their course of life should to be allowed or coerced into taking individual responsibility. Another important finding is that the current governing and organization of social work produce distance and detachment, and thus discourage caring subjects. This is a complex process in which an assemblage of different techniques and rationalities undermines the cultivation of a relationship between social worker and client. 1) The ideal of evidence-based practice favors rigid methods over a flexible and holistic approach. 2) Ideals of rationality, closely connected to notions of masculinity and professionalism, value objectivity and devalue and deter the surfacing of emotions. 3) Meticulous p, Sverige har ett internationellt rykte för att ha en omfattande och kvinnovänlig välfärd. Även om riktigheten i en sådan uppfattning sedan länge ifrågasatts har på senare år, likt i många andra Europeiska länder, det svenska välfärdssystemet genomgått en omfattande förändring i avseende på dess räckvidd, men också dess organisering och styrning. Fokus för denna studie är just denna organisering och styrning, och mer specifikt, hur detta påverkar ett av välfärdens kanske mest centrala område: socialt arbete. Genom att intervjua socialarbetare undersöks i denna studie uttryck för och konsekvenser av en sådan förändring, bland annat genom att undersöka hur könsbundna föreställningar och förväntningar är sammanflätade med det sociala arbetets organisering och styrning. I studien konstateras att socialarbetare erfar att deras arbete genomgått omfattande förändringar, vilket kopplas ihop med både organiseringen och styrningen av det sociala arbetet. Detta uttrycks både i de ideal som kringgärdar arbetet men också i dominerande arbetssätt. En sådan förändring är införandet av omfattande dokumentationsprocedurer av socialarbetarens arbete och kontakt med klienter, vilket medför att kontakten med klienterna blir ytligare. Dokumentationsprocedurerna utgör också en sorts kontroll av både klienterna och socialarbetarna själva. En annan förändring som konstateras är att nya organisationsmodeller och en förändrad ledarskapskultur skapar förväntningar på socialarbetarna att vara lojala med organisationen och ledningen snarare än klienterna. Bland annat utrycks detta genom förväntningar att inte protestera och skapa dålig stämning på arbetsplatsen, men också genom uttalade krav att spendera så lite resurser som möjligt på klienterna; korta behandlingstider, öppenvårdsalternativ och orimligt hårda krav för att få ekonomiskt bistånd. Detta legitimeras genom sammanväxningen av flera olika ideal; budgetmedvetenhet, att klienter inte mår bra av långa institutionsvistelser, men också att

As biosensing devices shrink smaller and smaller, they approach a scale in which single molecule electronic sensing becomes possible. Here, we review the operation of single-enzyme transistors made using single-walled carbon nanotubes. These novel hybrid devices transduce the motions and catalytic activity of a single protein into an electronic signal for real-time monitoring of the protein's activity. Analysis of these electronic signals reveals new insights into enzyme function and proves the electronic technique to be complementary to other single-molecule methods based on fluorescence. As one example of the nanocircuit technique, we have studied the Klenow Fragment (KF) of DNA polymerase I as it catalytically processes single-stranded DNA templates. The fidelity of DNA polymerases makes them a key component in many DNA sequencing techniques, and here we demonstrate that KF nanocircuits readily resolve DNA polymerization with single-base sensitivity. Consequently, template lengths can be directly counted from electronic recordings of KF's base-by-base activity. After measuring as few as 20 copies, the template length can be determined with <1 base pair resolution, and different template lengths can be identified and enumerated in solutions containing template mixtures.

Current genome-editing technologies introduce double-stranded (ds) DNA breaks at a target locus as the first step to gene correction. Although most genetic diseases arise from point mutations, current approaches to point mutation correction are inefficient and typically induce an abundance of random insertions and deletions (indels) at the target locus resulting from the cellular response to dsDNA breaks. Here we report the development of 'base editing', a new approach to genome editing that enables the direct, irreversible conversion of one target DNA base into another in a programmable manner, without requiring dsDNA backbone cleavage or a donor template. We engineered fusions of CRISPR/Cas9 and a cytidine deaminase enzyme that retain the ability to be programmed with a guide RNA, do not induce dsDNA breaks, and mediate the direct conversion of cytidine to uridine, thereby effecting a C→T (or G→A) substitution. The resulting 'base editors' convert cytidines within a window of approximately five nucleotides, and can efficiently correct a variety of point mutations relevant to human disease. In four transformed human and murine cell lines, second- and third-generation base editors that fuse uracil glycosylase inhibitor, and that use a Cas9 nickase targeting the non-edited strand, manipulate the cellular DNA repair response to favour desired base-editing outcomes, resulting in permanent correction of ~15-75% of total cellular DNA with minimal (typically ≤1%) indel formation. Base editing expands the scope and efficiency of genome editing of point mutations.