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Training medical image analysis models traditionally requires large amounts of expertly annotated imaging data which is time-consuming and expensive to obtain. One solution is to automatically extract scan-level labels from radiology reports. Previously, we showed that, by extending BERT with a per-label attention mechanism, we can train a single model to perform automatic extraction of many labels in parallel. However, if we rely on pure data-driven learning, the model sometimes fails to learn critical features or learns the correct answer via simplistic heuristics (e.g., that “likely” indicates positivity), and thus fails to generalise to rarer cases which have not been learned or where the heuristics break down (e.g., “likely represents prominent VR space or lacunar infarct” which indicates uncertainty over two differential diagnoses). In this work, we propose template creation for data synthesis, which enables us to inject expert knowledge about unseen entities from medical ontologies, and to teach the model rules on how to label difficult cases, by producing relevant training examples. Using this technique alongside domain-specific pre-training for our underlying BERT architecture i.e., PubMedBERT, we improve F1 micro from 0.903 to 0.939 and F1 macro from 0.512 to 0.737 on an independent test set for 33 labels in head CT reports for stroke patients. Our methodology offers a practical way to combine domain knowledge with machine learning for text classification tasks.

In this feature topic, we explore the burgeoning trend to employ templates in qualitative research. To understand authors' motivations to use templates and perceptions regarding template use in the scholarly community, we conducted an interview study with 21 interviewees who had published qualitative research in one of nine premier management journals between 2014 and 2018. Our analysis identified four key tensions in template use: structure versus restriction, convention versus innovativeness, legitimization versus obscuration, and instrumentality versus craft. We discuss these tensions and their implications for the practice and evaluation of qualitative research. We then introduce the eight papers included in this feature topic. Each of them addresses and explores specific aspects of the origins and limitations of template use, whilst providing insights and guidance for future qualitative research. We envisage this feature topic to be a catalyst for discourse amongst scholars, engaging with contemporary trends and tensions to pave new pathways that embrace the diversity and plurality of qualitative approaches. [ABSTRACT FROM AUTHOR]

Trends toward convergence on common methodologies and standardized templates restrict the diversity of qualitative methods in organizational research. Considering that graduate education is a critical process in the socialization of researchers into the norms and dominant practices of their discipline, graduate students' socialization into research methodologies is vital for understanding methodological convergence. The purpose of our study was to understand how graduate students' socialization shapes their methodological and paradigmatic preferences. Showcasing methodological bricolage as an alternative to qualitative templates, we constructed a research design that combined thematic, discourse, and narrative analyses to investigate graduate students' reflections throughout a qualitative methods course introducing alternative research paradigms. Our findings highlight the role of institutional, disciplinary, and personal influences as well as identity work in researchers' socialization and trace alternative trajectories by which socialization and methodological identity construction processes may unfold. We offer a sketch of methodological socialization and suggest that its understanding should be central to nurturing paradigmatic and methodological plurality in qualitative research. We conclude with implications for future research and for research methods training. [ABSTRACT FROM AUTHOR]

Using a translation lens, we explore templates for writing ethnography in organization studies and their evolution over time through the analysis of all ethnographic papers published in the premier journal Administrative Science Quarterly, 1956-2018. We found three templates of ethnographic writing. Few early ethnographic papers resemble travelogues, as they use theory to explain a unique case based on firsthand experiences of the author. Most studies read like detective stories, using extensive, quantified data from a case and systematically analyzing it to advance theory. This template has remained predominant over time. Finally, some ethnographic papers read like postmodern detective stories, in that they attempt to create knowledge from lived experience, while also hinting at the partiality of this knowledge. This template appeared around the turn of the century but is today rare. The overall low number of ethnographies and the lasting hegemony of the ethnography as detective story template reflect the strict disciplining of ethnography into the emulation of positivist research, constraining knowledge creation in organization studies. We conclude by offering researchers some strategies to recover the strengths of templates available in the past to broaden the boundaries of existing norms for writing ethnography today. [ABSTRACT FROM AUTHOR]

Researchers are exposed to multiple interpretive challenges in the journey from field data to theoretical understanding. A common response to these challenges is to turn to the guidance of templates such as the Gioia methodology—currently a preferred template for interpretive management research. Given its popularity, we examine how this methodology approaches the interpretive process of fieldwork. We find that the inductive route to theory that it offers does not address the challenges of interpretation. As an alternative, we propose a return to the epistemological tradition of hermeneutics. We argue that fieldwork informed by a hermeneutic orientation is able to generate credible and novel theory by confronting the challenges of interpretation head on. This process cannot be represented by the orderly steps of a template. We argue that a return to a hermeneutic orientation opens the way to more plausible and insightful theories based on interpretive rather than procedural rigor, and we offer a set of heuristics to guide both researchers and reviewers along this path. [ABSTRACT FROM AUTHOR]

Well-accepted methodological practices require thoughtful and appropriate use to avoid becoming mindlessly applied and distorted. We review how ideas from Langley's (1999) process data analysis article have been used in practice. By closely analyzing 176 empirical articles in management and organization journals from 1999 to 2019, we highlight how Langley's ideas have been applied in exemplary ways and adapted through bricolage (a central concept in qualitative methods). In many instances, we found that Langley's ideas have been given a cursory nod or have even been distorted (what we label as considerations); thus, we recommend how to avoid replicating these applications. We discuss process data analysis tools from Langley's article that have been underused (labeled overlooked) but that may be valuable in future process studies. Through our deep reading and review, we highlight how using Langley's ideas can enhance the transparency and trustworthiness of a qualitative process study and mitigate her ideas' movement toward a mindless template application. [ABSTRACT FROM AUTHOR]

The domain of qualitative research is replete with templates, standard protocols for the analysis of qualitative data. The use of such templates has sometimes been considered as automatically enhancing the rigor of qualitative research. In this article, we challenge the view that in the context of qualitative research, rigor is tied into the application of established protocols. Instead, we argue that rigor emanates from the way in which researchers engage in a deliberate reasoning process of inferring theoretical claims from their data. Such reasoning exists outside of templates, although it may make use of templates. Framing rigor as an emergent quality of reasoning, we distill the main processes through which qualitative researchers derive inferences from data and provide criteria for reflecting on the rigor with which they do so. We then extend these criteria into a set of practical recommendations through the presentation of examples and the framing of questions to focus researchers' thinking on the application of the criteria. In doing so, we aim to help qualitative researchers to conduct research that leads to rigorously derived theoretical insights without having to resort to templates to attempt to do so. [ABSTRACT FROM AUTHOR]

Biomimicking organ mannequins with not only lifelike biological geometries but also virtually constituting connected circulation channels for exchanging substances are critical for in vitro biomedical applications, yet the big challenges remain. This paper reports a big step toward the goal to achieve hydrogel‐based organ mannequins with internal channels and a cavity, gradient structures, and a physiological environment of organs for in vitro purposes via metal ions‐induced interface supramolecular assembly of hydrogel layers on the thermally splitting templates. The templates composed of gelatin and ι‐carrageenan are built through direct ink writing, which are employed as the supports to in situ grow the alginate/Ca2+ hydrogel layers by rapid diffusion‐induced gelation process. Removing the hydrogel templates based on sol–gel conversion can readily yield hydrogel architectures with connected channels, structural integrity, and favorable physicochemical properties. Proof‐of‐concept hydrogel mannequins including the branched vascular replicas, digestive system, distal lung subunit, and glomerulus with mechanical robustness are engineered from replicating the tubular structure to imitate the basic profiles of organs. It is believed that this protocol paves a versatile way to construct hydrogel‐based biomimicking mannequins with cavity structures that can be used for in vitro biomedical training, testing, pharmacology, etc. [ABSTRACT FROM AUTHOR]

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

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.

Viruses in the Reoviridae, like the triple-shelled human rotavirus and the single-shelled insect cytoplasmic polyhedrosis virus (CPV), all package a genome of segmented double-stranded RNAs (dsRNAs) inside the viral capsid and carry out endogenous messenger RNA synthesis through a transcriptional enzyme complex (TEC). By direct electron-counting cryoelectron microscopy and asymmetric reconstruction, we have determined the organization of the dsRNA genome inside quiescent CPV (q-CPV) and the in situ atomic structures of TEC within CPV in both quiescent and transcribing (t-CPV) states. We show that the ten segmented dsRNAs in CPV are organized with ten TECs in a specific, non-symmetric manner, with each dsRNA segment attached directly to a TEC. The TEC consists of two extensively interacting subunits: an RNA-dependent RNA polymerase (RdRP) and an NTPase VP4. We find that the bracelet domain of RdRP undergoes marked conformational change when q-CPV is converted to t-CPV, leading to formation of the RNA template entry channel and access to the polymerase active site. An amino-terminal helix from each of two subunits of the capsid shell protein (CSP) interacts with VP4 and RdRP. These findings establish the link between sensing of environmental cues by the external proteins and activation of endogenous RNA transcription by the TEC inside the virus.

Telomerase is required to maintain repetitive G-rich telomeric DNA sequences at chromosome ends. To do so, the telomerase reverse transcriptase (TERT) subunit reiteratively uses a small region of the integral telomerase RNA (TER) as a template. An essential feature of telomerase catalysis is the strict definition of the template boundary to determine the precise TER nucleotides to be reverse transcribed by TERT. We report the 3-Å crystal structure of the Tetrahymena TERT RNA-binding domain (tTRBD) bound to the template boundary element (TBE) of TER. tTRBD is wedged into the base of the TBE RNA stem-loop, and each of the flanking RNA strands wraps around opposite sides of the protein domain. The structure illustrates how the tTRBD establishes the template boundary by positioning the TBE at the correct distance from the TERT active site to prohibit copying of nontemplate nucleotides.

Copyright of Museum: Museum & Regional Studies is the property of National Museum and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nowadays our society is mostly depending on the digitalization and automation. The main aim of this project is developed OCR code for decoding the pan card number. OCR is an optical character recognition and is the mechanical or electronic translation of images. OCR is a field of researching pattern recognition, artificial intelligence and machine vision. In this project we can decode the pan card number and it gives the details such as income tax transactions, number of loans taken, cibil score, returns and loan status of the card holder so that we can know the every information of the holder. We can get the information easily about how many are paying the income tax to the government regularly. For this we are using MATLAB software. In this we can track the details of owner by taking the photograph of pan card and that will be stored, processed in the OCR and details will be displayed. [ABSTRACT FROM AUTHOR]

This paper considers Lagrangian finite elements for structural dynamics constructed with cubic displacement shape functions. The method of templates is used to investigate the construction of accurate mass-stiffness pairs. This method introduces free parameters that can be adjusted to customize elements according to accuracy and rank-sufficiency criteria. One- and two-dimensional Lagrangian cubic elements with only translational degrees of freedom (DOF) carry two additional nodes on each side, herein called side nodes or SN. Although usually placed at the third-points, the SN location may be adjusted within geometric limits. The adjustment effect is studied in detail using symbolic computations for a bar element. The best SN location is taken to be that producing accurate approximation to the lowest natural frequencies of the continuum model. Optimality is investigated through Fourier analysis of the propagation of plane waves over a regular infinite lattice of bar elements. Focus is placed on the acoustic branch of the frequency-vs.-wavenumber dispersion diagram. It is found that dispersion results using the fully integrated consistent mass matrix (CMM) are independent of the SN location whereas its low- frequency accuracy order is O(K8), where K is the dimensionless wave number. For the diagonally lumped mass matrix (DLMM) constructed through the HRZ scheme, two optimal SN locations are identified, both away from third-points and of accuracy order O(K8). That with the smallest error coefficient corresponds to the Lobatto 4- point integration rule. A special linear combination of CMM and DLMM with nodes at the Lobatto points yields an accuracy of O(K10) without any increase in the computational effort over CMM. The effect of reduced integration (RI) on both mass and stifness matrices is also studied. It is shown that singular mass matrices can be constructed with 2-and 3-point RI rules that display the same optimal accuracy of the exactly integrated case, at the cost of introducing spurious modes. The optimal SN location in two-dimensional, bicubic, isoparametric plane stress quadrilateral elements is briefly investigated by numerical experiments. The frequency accuracy of flexural modes is found to be fairly insensitive to that position, whereas for bar-like modes it agrees with the one-dimensional results. [ABSTRACT FROM AUTHOR]

Solar energy storage and conversion have remained significant global challenges. This article discusses how to fabricate a polymeric solar thermal fuel (P‐STF) composite with unique thermal storage abilities. In this regard, we aim at developing a novel method for dispersing multi‐walled carbon nanotubes (MWCNTs) functionalized with azobenzene molecules (modified azobenzene molecules) in ethylene‐vinyl acetate (EVA). The modification of azobenzene (functionalization) enhances the energy storage density of AZO molecules, and the addition of fillers (MWCNT) leads to the production of the P‐STF composite with the potential to store and convert solar energy to thermal energy. The differential scanning calorimetry (DSC) test verifies the P‐STF composite's capacity to absorb solar energy and release it as heat. Thus, the uncharged nanocomposites required heat energy at the melting point temperature of EVA (Enthalpy 18.392 J/g). However, the EVA‐AZO‐MWCNT 10% and EVA‐AZO‐MWCNT 5% nanocomposites released heat energy rather than requiring it to melt with enthalpy −37.6526 and −1.2609 J/g, respectively, which indicates the heat release in the P‐STF composite. Moreover, oscillatory shear rheological measurement (RMS) and field emission scanning electron microscopy (FESEM) demonstrate that modified azobenzene (MWCNT‐AZO) is well dispersed in the polymer matrix (EVA). [ABSTRACT FROM AUTHOR]

Correlations of rock-physics model inputs are important to know to help design informative prior models within integrated reservoir-characterization workflows. A Bayesian framework is optimal to determine such correlations. Within that framework, we use velocity and porosity measurements on unconsolidated, dry, and clean sands. Three pressure- and three porosity-dependent rock-physics models are applied to the data to examine relationships among the inputs. As with any Bayesian formulation, we define a prior model and calculate the likelihood in order to evaluate the posterior. With relatively few inputs to consider for each rock-physics model, we found that sampling the posterior exhaustively to be convenient. The results of the Bayesian analyses are multivariate histograms that indicate most likely values of the input parameters given the data to which the rock-physics model was fit. When the Bayesian procedure is repeated many times for the same data, but with different prior models, correlations emerged among the input parameters in a rock-physics model. These correlations were not known previously. Implications, for the pressure- and porosity-dependent models examined here, are that these correlations should be utilized when applying these models to other relevant data sets. Furthermore, additional rock-physics models should be examined similarly to determine any potential correlations in their inputs. These correlations can then be taken advantage of in forward and inverse problems posed in reservoir characterization.

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.

Technologies that valorize carbon dioxide are becoming an increasingly relevant component of the portfolio of solutions necessary to mitigate and reverse climate change. Assessing the environmental and economic characteristics of these technologies early in their developmental trajectories can help technologists either efficiently accelerate emissions reductions and commercialization or realize potential infeasibility and direct resources toward better opportunities. To aid in such assessments, this article constructs a typology of carbon removal and utilization technologies and identifies specific pathways in need of early-stage life cycle assessment (LCA) and techno-economic assessment (TEA) templates. Based on published literature and project experience, example LCA and TEA templates are developed for high-priority pathways with relatively low technology readiness levels including direct air capture, chemical synthesis, algae products, carbonated concrete, and carbonated aggregates. The templates attempt to capture the most important elements of early-stage LCA and TEA in an easily understandable and usable manner that still allows for reliable, order-of-magnitude estimations and hotspot analysis. Opportunities for other practitioners to use and build upon the templates are also discussed.

Air pollution threats to human health have increased awareness of the role of filter units in air cleaning applications. As an ideal energy-saving strategy for air filters, the slip effect on nanofiber surfaces can potentially overcome the trade-off between filtration efficiency and pressure drop. However, the potential of the slip effect in nanofibrous structures is significantly limited by the tight nanofiber stacks. In this study, trichome-like biomimetic (TLB) air filters with 3D-templated silicone nanofilaments (average diameter: ≈74 nm) are prepared based on an in situ chemical vapor deposition (CVD) method inspired by plant purification. Theoretical modeling and experimental results indicate that TLB air filters make significant use of the slip effect to overcome the efficiency-resistance tradeoff. The selectable filter class (up to U15, ≈99.9995%) allows TLB air filters to meet various requirements, and their integral filtration performance surpasses that of most commodity air filters, including melt-blown cloth, ePTFE membranes, electrospun mats, and glass fiber paper. The proposed strategy directly transforms commercial filter media and filters into TLB air filters using a bottom-up, one-step approach. As a proof-of-concept, reusable N95 respirators and air purifiers equipped with TLB air filters are fabricated, overcoming the limitations of existing filter designs and fabrication methods., (© 2024 Wiley‐VCH GmbH.)

Longevity is a long‐standing concern for organic–inorganic hybrid perovskite solar cells (PSCs). Recently, the use of low dimensional perovskite has been proven to be a promising strategy to improve the stability of PSCs. Herein, it is demonstrated that 1D perovskitoid based on 2‐diethylaminoethylchloride cations can act as a template to induce 1D@3D perovskite structure, leading to smoother surface texture, longer charge‐carrier lifetime, smaller residual tensile strain, and reduced surface‐defect density in the perovskite film. With this strategy, highly efficient and stable 1D@3D PSC with excellent reproducibility, showing a champion power conversion efficiency (PCE) of 22.9% under standard AM 1.5 G one sun illumination is realized. The unencapsulated optimized devices can retain 94.7%, 92.4%, and 90.0% of their initial PCEs for 2100, 2200, and 2200 h under ambient air, 85 °C and illumination conditions, respectively. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic had put pressure on various national healthcare systems, due to the lack of health professionals and exhaustion of those avaliable, as well as lack of interoperability and inability to restructure their IT systems. Therefore, the restructuring of institutions at all levels is essential, especially at the level of their information systems. Furthermore, the COVID-19 pandemic had arrived in Portugal at March 2020, with a breakout on the northern region. In order to quickly respond to the pandemic, the CHUP healthcare institution, known as a research center, has embraced the challenge of developing and integrating a new approach based on the openEHR standard to interoperate with the institution's existing information and its systems. An openEHR clinical modelling methodology was outlined and adopted, followed by a survey of daily clinical and technical requirements. With the arrival of the virus in Portugal, the CHUP institution has undergone through constant changes in their working methodologies as well as their openEHR modelling. As a result, an openEHR patient care workflow for COVID-19 was developed. [ABSTRACT FROM AUTHOR]

Siloxanes have evolved into a multi‐million dollar business due to their manifold of commercial and industrial applications. As siloxanes have high hydrophobicity, low basicity, high flexibility and also high chemical inertness in common, their chemistry differs significantly from that of organic ethers. The discovery of organic crown ethers, for instance, is commonly accepted as the birth of synthetic host‐guest chemistry. Regarding the chemical properties of siloxanes, cyclic siloxanes which formally resemble silicon analogues of crown ethers, have received considerably less interest in terms of their host‐guest chemistry. Hence, only little is known about siloxane coordination chemistry in the chemical community and the number of published works in this field has been very low till lately. In the last few years, the field has significantly advanced and elegant methods were established to enable the Si−O−Si unit for coordination. This review therefore summarizes the recent developments in the field, recapitulates the historical aspects of siloxane coordination chemistry and describes the specific Si−O bond character with regard to different siloxane linkages. Implications on Si−O bond activation are included and the limits of siloxane coordination are redefined. [ABSTRACT FROM AUTHOR]

Copyright of Question (1669-6581) is the property of Universidad Nacional de La Plata and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

DNA methylation at selective cytosine residues (5-methylcytosine (5mC)) and their removal by TET-mediated DNA demethylation are critical for setting up pluripotent states in early embryonic development. TET enzymes successively convert 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), with 5fC and 5caC subject to removal by thymine DNA glycosylase (TDG) in conjunction with base excision repair. Early reports indicate that 5fC and 5caC could be stably detected on enhancers, promoters and gene bodies, with distinct effects on gene expression, but the mechanisms have remained elusive. Here we determined the X-ray crystal structure of yeast elongating RNA polymerase II (Pol II) in complex with a DNA template containing oxidized 5mCs, revealing specific hydrogen bonds between the 5-carboxyl group of 5caC and the conserved epi-DNA recognition loop in the polymerase. This causes a positional shift for incoming nucleoside 5'-triphosphate (NTP), thus compromising nucleotide addition. To test the implication of this structural insight in vivo, we determined the global effect of increased 5fC/5caC levels on transcription, finding that such DNA modifications indeed retarded Pol II elongation on gene bodies. These results demonstrate the functional impact of oxidized 5mCs on gene expression and suggest a novel role for Pol II as a specific and direct epigenetic sensor during transcription elongation.

Telomerase is an enzyme that adds repetitive DNA sequences to the ends of chromosomes and consists of two main subunits: the telomerase reverse transcriptase (TERT) protein and an associated telomerase RNA (TER). The telomerase essential N-terminal (TEN) domain is a conserved region of TERT proposed to mediate DNA substrate interactions. Here, we have employed single molecule telomerase binding assays to investigate the function of the TEN domain. Our results reveal telomeric DNA substrates bound to telomerase exhibit a dynamic equilibrium between two states: a docked conformation and an alternative conformation. The relative stabilities of the docked and alternative states correlate with the number of basepairs that can be formed between the DNA substrate and the RNA template, with more basepairing favoring the docked state. The docked state is further buttressed by the TEN domain and mutations within the TEN domain substantially alter the DNA substrate structural equilibrium. We propose a model in which the TEN domain stabilizes short RNA-DNA duplexes in the active site of the enzyme, promoting the docked state to augment telomerase processivity.

Variations in the sugar component (ribose or deoxyribose) and the nature of the phosphodiester linkage (3'-5' or 2'-5' orientation) have been a challenge for genetic information transfer from the very beginning of evolution. RNA polymerase II (pol II) governs the transcription of DNA into precursor mRNA in all eukaryotic cells. How pol II recognizes DNA template backbone (phosphodiester linkage and sugar) and whether it tolerates the backbone heterogeneity remain elusive. Such knowledge is not only important for elucidating the chemical basis of transcriptional fidelity but also provides new insights into molecular evolution. In this study, we systematically and quantitatively investigated pol II transcriptional behaviors through different template backbone variants. We revealed that pol II can well tolerate and bypass sugar heterogeneity sites at the template but stalls at phosphodiester linkage heterogeneity sites. The distinct impacts of these two backbone components on pol II transcription reveal the molecular basis of template recognition during pol II transcription and provide the evolutionary insight from the RNA world to the contemporary 'imperfect' DNA world. In addition, our results also reveal the transcriptional consequences from ribose-containing genomic DNA.

Los memes de internet son una de las formas comunicacionales participativas más características de la web 2.0. Con el objetivo de ser humorísticos pero también expresar sentimientos, ideas y opiniones de formas creativas y ser fácilmente comprensibles, los usuarios crean memes basados en formatos preexistentes llamados usualmente templates. En este artículo analizamos el uso de templates en memes de imagen fija desde una perspectiva empírica y teórica y también otras maneras en las que los memes están estructurados semióticamente por formas preexistentes.

Longitudinal non-human primate neuroimaging has the potential to greatly enhance our understanding of primate brain structure and function. Here we describe its specific strengths, compared to both cross-sectional non-human primate neuroimaging and longitudinal human neuroimaging, but also its associated challenges. We elaborate on factors guiding the use of different analytical tools, subject-specific versus age-specific templates for analyses, and issues related to statistical power.

Facilitated by recent advances using CRISPR/Cas9, genome editing technologies now permit custom genetic modifications in a wide variety of organisms. Ideally, modified animals could be both efficiently made and easily identified with minimal initial screening and without introducing exogenous sequence at the locus of interest or marker mutations elsewhere. To this end, we describe a coconversion strategy, using CRISPR/Cas9 in which screening for a dominant phenotypic oligonucleotide-templated conversion event at one locus can be used to enrich for custom modifications at another unlinked locus. After the desired mutation is identified among the F1 progeny heterozygous for the dominant marker mutation, F2 animals that have lost the marker mutation are picked to obtain the desired mutation in an unmarked genetic background. We have developed such a coconversion strategy for Caenorhabditis elegans, using a number of dominant phenotypic markers. Examining the coconversion at a second (unselected) locus of interest in the marked F1 animals, we observed that 14-84% of screened animals showed homologous recombination. By reconstituting the unmarked background through segregation of the dominant marker mutation at each step, we show that custom modification events can be carried out recursively, enabling multiple mutant animals to be made. While our initial choice of a coconversion marker [rol-6(su1006)] was readily applicable in a single round of coconversion, the genetic properties of this locus were not optimal in that CRISPR-mediated deletion mutations at the unselected rol-6 locus can render a fraction of coconverted strains recalcitrant to further rounds of similar mutagenesis. An optimal marker in this sense would provide phenotypic distinctions between the desired mutant/+ class and alternative +/+, mutant/null, null/null, and null/+ genotypes. Reviewing dominant alleles from classical C. elegans genetics, we identified one mutation in dpy-10 and one mutation in sqt-1 that meet these criteria and demonstrate that these too can be used as effective conversion markers. Coconversion was observed using a variety of donor molecules at the second (unselected) locus, including oligonucleotides, PCR products, and plasmids. We note that the coconversion approach described here could be applied in any of the variety of systems where suitable coconversion markers can be identified from previous intensive genetic analyses of gain-of-function alleles.

Background: Osteochondroma (OC) is one of the most common benign tumors of the long bones, but it rarely occurs in the maxillofacial skeleton. However, mandibular condylar OC often leads to severe facial deformity in affected patients, including facial asymmetry, deviation of the chin, and malocclusion. This study aimed to explore the clinical application of individualized 3D-printed templates to accurately and effectively treat condylar OC. Methods: A total of 8 patients with mandibular condylar OC were treated from July 2015 to August 2021. The enrolled patients (5 women and 3 men) had a median age of 27 years (range: 21–32 years). All patients exhibited symptoms of facial asymmetry and occlusal disorders preoperatively. The digital software used to virtually design the process consisted of three-dimensional reconstruction, 3D-cephalometry analysis, virtual surgery, individualized templates, and postoperative facial soft-tissue prediction. A set of 3D-printed templates (DOS and DOT) were used in all cases to stabilize the occlusion and guide the osteotomy. Then, pre- and post-operative complications, mouth opening, clinical signs, and the accuracy of the CT imaging analysis were all evaluated. All the measurement data were presented as means ± SD; Bonferroni and Tamhane T2 multiple comparison tests were used to examine the differences between the groups. Results: All patients healed uneventfully. None of the patients exhibited facial nerve injury at follow-up. In comparing the condylar segments with T0p and T1, the average deviation of the condylar segments was 0.5796 mm, indicating that the post-operative reconstructed condyles showed a high degree of similarity to the reconstruction results of the virtual surgical plan. Conclusions: Individualized 3D-printed templates simplified surgical procedures and improved surgical accuracy, proving to be an effective method for the treatment of patients with slight asymmetric deformities secondary to condylar OC.

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. [ABSTRACT FROM AUTHOR]

The interdisciplinary research (philology, typology, morphology, phonology) presented here explores the role of gender in the meaning and morphology of Coptic nouns. Coptic has a predominantly grammatical gender system, albeit with a niche for semantically based gender assignment. The gender system marks a three-way semantic contrast between a [male] versus a [female] versus an [unspecified] gender value, even where the morphology draws only a two-way distinction between grammatical masculine and feminine gender. By integrating quantitative data and morphophonological analysis, we shall argue that masculine gender is morphologically unmarked. Although no discrete morpheme can be identified, feminine gender is always morphologically marked on nouns. Masculine and feminine nouns are distinguished in terms of their templatic structure, which interacts in complex ways with vowel distributions, stress assignment, and noun class. [ABSTRACT FROM AUTHOR]

Globally, 74 countries have domestic investment laws that mention investor-state arbitration and 42 of these laws provide consent to it. That is, they give foreign investors the right to bypass national courts and bring claims directly to arbitration. What explains this variation, and why do any governments include investor-state arbitration in domestic legislation? We argue that governments incorporate arbitration into their domestic laws because doing so was labelled 'international best practice' by specialist units at the World Bank. We introduce the concept of asymmetric diffusion, which occurs when a policy is framed as international best practice but only recommended to a subset of states. No developed state consents to arbitration in their domestic law, nor does the World Bank recommend that they do so. Yet we show that governments who receive technical assistance from the World Bank's Foreign Investment Advisory Service are more likely to include arbitration in their laws. We first use event history analysis and find that receiving World Bank technical assistance is an exceptionally strong predictor of domestic investment laws with arbitration. Then we illustrate our argument with a case study of the Kyrgyz Republic's 2003 law. [ABSTRACT FROM AUTHOR]