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In speech production, the anatomical morphology forms the substrate on which the speakers build their articulatory strategy to reach specific articulatory-acoustic goals. The aim of this study is to characterize morphological inter-speaker variability by building a shape model of the full vocal tract including hard and soft structures. Static magnetic resonance imaging data from 41 speakers articulating altogether 1947 phonemes were considered, and the midsagittal articulator contours were manually outlined. A phoneme-independent average-articulation representative of morphology was calculated as the speaker mean articulation. A principal component analysis-driven shape model was derived from average-articulations, leading to five morphological components, which explained 87% of the variance. Almost three-quarters of the variance was related to independent variations of the horizontal oral and vertical pharyngeal lengths, the latter capturing male-female differences. The three additional components captured shape variations related to head tilt and palate shape. Plane wave propagation acoustic simulations were run to characterize morphological components. A lengthening of 1 cm of the vocal tract in the vertical or horizontal directions led to a decrease in formant values of 7%–8%. Further analyses are required to analyze three-dimensional variability and to understand the morphological-acoustic relationships per phoneme. Average-articulations and model code are publicly available ( https://github.com/tonioser/VTMorphologicalModel ).

Abstract Inflammation is a hallmark in severe diseases such as atherosclerosis and non-alcohol-induced steatohepatitis (NASH). In the development of inflammation, prostaglandins, especially prostaglandin E2 (PGE2), are major players alongside with chemo- and cytokines, like tumor-necrosis-factor alpha (TNFα) and interleukin-1 beta (IL-1β). During inflammation, PGE2 synthesis can be increased by the transcriptional induction of the two key enzymes: cyclooxygenase 2 (COX-2), which converts arachidonic acid to PGH2, and microsomal prostaglandin E2 synthase 1 (mPGES-1), which synthesizes PGE2 from PGH2. Both COX-2 and mPGES-2 were induced by a dietary intervention where mice were fed a fatty acid-rich and, more importantly, cholesterol-rich diet, leading to the development of NASH. Since macrophages are the main source of PGE2 synthesis and cholesterol is predominantly transported as LDL, the regulation of COX-2 and mPGES-1 expression by native LDL was analyzed in human macrophage cell lines. THP-1 and U937 monocytes were differentiated into macrophages, through which TNFα and PGE-2 induced COX-2 and mPGES-1 expression by LDL could be analyzed on both mRNA and protein levels. In addition, the interaction of LDL- and EP receptor signal chains in COX-2/mPGES-1 expression and PGE2-synthesis were analyzed in more detail using EP receptor specific agonists. Furthermore, the LDL-mediated signal transduction in THP-1 macrophages was analyzed by measuring ERK and Akt phosphorylation as well as transcriptional regulation of transcription factor Egr-1. COX-2 and mPGES-1 were induced in both THP-1 and U937 macrophages by the combination of TNFα and PGE2. Surprisingly, LDL dose-dependently increased the expression of mPGES-1 but repressed the expression of COX-2 on mRNA and protein levels in both cell lines. The interaction of LDL and PGE2 signal chains in mPGES-1 induction as well as PGE2-synthesis could be mimicked by through simultaneous stimulation with EP2 and EP4 agonists. In THP-1 macrophages, LDL induced Akt-phosphorylation, which could be blocked by a PI3 kinase inhibitor. Alongside blocking Akt-phosphorylation, the PI3K inhibitor inhibited LDL-mediated mPGES-1 induction; however, it did not attenuate the repression of COX-2 expression. LDL repressed basal ERK phosphorylation and expression of downstream transcription factor Egr-1, which might lead to inhibition of COX-2 expression. These findings suggest that simultaneous stimulation with a combination of TNFα, PGE2, and native LDL-activated signal chains in macrophage cell lines leads to maximal mPGES-1 activity, as well repression of COX-2 expression, by activating PI3K as well as repression of ERK/Egr-1 signal chains.

Background Cas12a (formerly known as Cpf1), the class II type V CRISPR nuclease, has been widely used for genome editing in mammalian cells and plants due to its distinct characteristics from Cas9. Despite being one of the most robust Cas12a nucleases, LbCas12a in general is less efficient than SpCas9 for genome editing in human cells, animals, and plants. Results To improve the editing efficiency of LbCas12a, we conduct saturation mutagenesis in E. coli and identify 1977 positive point mutations of LbCas12a. We selectively assess the editing efficiency of 56 LbCas12a variants in human cells, identifying an optimal LbCas12a variant (RVQ: G146R/R182V/E795Q) with the most robust editing activity. We further test LbCas12a-RV, LbCas12a-RRV, and LbCas12a-RVQ in plants and find LbCas12a-RV has robust editing activity in rice and tomato protoplasts. Interestingly, LbCas12a-RRV, resulting from the stacking of RV and D156R, displays improved editing efficiency in stably transformed rice and poplar plants, leading to up to 100% editing efficiency in T0 plants of both plant species. Moreover, this high-efficiency editing occurs even at the non-canonical TTV PAM sites. Conclusions Our results demonstrate that LbCas12a-RVQ is a powerful tool for genome editing in human cells while LbCas12a-RRV confers robust genome editing in plants. Our study reveals the tremendous potential of these LbCas12a variants for advancing precision genome editing applications across a wide range of organisms.

Protein–ligand interactions are increasingly profiled at high throughput using affinity selection and massively parallel sequencing. However, these assays do not provide the biophysical parameters that most rigorously quantify molecular interactions. Here we describe a flexible machine learning method, called ProBound, that accurately defines sequence recognition in terms of equilibrium binding constants or kinetic rates. This is achieved using a multi-layered maximum-likelihood framework that models both the molecular interactions and the data generation process. We show that ProBound quantifies transcription factor (TF) behavior with models that predict binding affinity over a range exceeding that of previous resources; captures the impact of DNA modifications and conformational flexibility of multi-TF complexes; and infers specificity directly from in vivo data such as ChIP-seq without peak calling. When coupled with an assay called KD-seq, it determines the absolute affinity of protein–ligand interactions. We also apply ProBound to profile the kinetics of kinase–substrate interactions. ProBound opens new avenues for decoding biological networks and rationally engineering protein–ligand interactions.

Monitoring the treatment outcome of canine cystic endometrial hyperplasia-pyometra complex (CEH-P) is essential to identify nonresponding patients who might require a rapid intervention to avoid life-threatening conditions. Uterine artery Doppler characterization may contribute to monitoring medically treated CEH-P, but published studies are currently lacking. Therefore, the aim of this longitudinal prospective observational study was to evaluate uterine artery resistance changes in the medical treatment of female dogs with CEH-P. Twelve diestrous female dogs suffering from CEH-P were treated with a combined protocol of cabergoline, cloprostenol, and antibiotics. The animals were clinically and ultrasonographically evaluated before the beginning of treatment (day 0) and on days 3, 7, 14, 21, and 28. The widest transverse diameter and luminal diameter of uterine horns were measured, as well as the peak systolic velocity (PSV) and end diastolic velocity (EDV) of uterine arteries. The resistance index (RI), pulsatility index (PI), and notch deep index (NDI) were calculated. On day 3, nine of 12 animals showed clinical improvement. In all these female dogs, the widest transverse sectional diameter (P 0.01), luminal diameter (P 0.01), PSV (P 0.01), and EDV (P 0.01) progressively decreased, while RI (P 0.01), PI (P 0.01), and NDI (P 0.01) increased up to day 21. In nonresponding dogs (3/12), Doppler parameters remained unchanged. Although comparisons of PSV, EDV, and NDI were significantly different, these results should be cautiously interpreted due to the low statistical power. female dogs that responded to this treatment showed an increase in uterine artery resistance, along with clinical and ultrasonographic improvement.

Additional file 3. Review history.

Additional file 2: Table S1. Positive mutations identified in the LbCas12a saturation screen. Table S2. T-DNA vectors used in this study. Table S3. Oligos used in this study.

Additional file 1: Figure S1. Double mutations on LbCas12atransferred from AsCas12a Ultra reduced editing efficiency in HEK293 cells. Figure S2. Editing efficiency of 24 novel LbCas12a mutant proteins in HEK293 cells using the T7EI assay. Figure S3. Targeted mutagenesis by LbCas12a variants in rice and tomato protoplasts using low-concentration RNP delivery. A, single crRNA was delivered using 0.001 µM RNP in rice protoplast; B, multiplex 6 crRNAs were delivered using 0.006 µM RNP in tomato protoplast. Figure S4. Genotypes of T0 plants at 5 target sites of LbCas12a variants. Figure S5. Off-target analysis of LbCas12 variants in T0 rice plants.As per journal requirements, every additional file must have a corresponding caption. In this regard, please be informed that the caption was taken from the additional e-file itself. Please advise if the action taken is appropriate and amend if necessary.The captions look good!

The COVID-19 pandemic has led to face-to-face activities being developed in a virtual format that often offers a poor experience in areas such as education. Virtual Learning Environments have improved in recent years thanks to new technologies such as Virtual Reality or Chatbots. However, creating Virtual Learning Environments requires advanced programming knowledge, so this work is aimed to enable teachers to create these new environments easily. This work presents a set of extensions for App Inventor that facilitate the authoring of mobile learning apps that use Chatbots in a Virtual Reality environment, while simultaneously monitoring of student activity. This proposal is based on integrating block-based languages and Business Process Model and Notation diagrams. The developed extensions were successfully implemented in an educational app called Let’s date!. A quantitative analysis of the use of these extensions in App Inventor was also carried out, resulting in a significant reduction in the number of blocks required. The proposed contribution has demonstrated its validity in creating virtual learning environments through visual programming and modelling, reducing development complexity.

This position paper, written by members of International Union of Angiology (IUA) Youth Committee, shows an overview of coagulation system and laboratory tests, analysis of medical therapies (older and newer), medication discontinuation/restart recommendations, bridging therapy recommendations, and an overview of hemostatic agents used in the operating room.

Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder that presents with multi-organ involvement, including but not limited to hamartomas in the brain, eyes, heart, lung, liver, kidney, and skin. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory, autoimmune, demyelinating, central nervous system disorder, targeting the optic nerves and spinal cord. We report a 30-year-old woman with TSC who developed tingling in the legs that gradually involved her abdomen. Additional symptoms included severe vomiting that lasted for a week and spasms in her legs. One month later, she was hospitalized due to difficulty ambulating and tingling in her hands. Magnetic resonance imaging (MRI) of her spine showed longitudinally extensive upper cervical and lower thoracic cord signal changes. MRI scan of her brain showed few non-specific T2 signal changes along with cortical and subcortical tubers. Aquaporin (AQP4) IgG antibody was found to be positive in both serum and cerebrospinal fluid. Accordingly, she was diagnosed with NMOSD, treated with a 5-day course of intravenous steroids, followed by 5 sessions of plasma exchange. After her initial improvement, she was started on rituximab as maintenance therapy. Two years later, she is clinically stable, and her follow-up MRI showed marked improvement.

Inflammation is a hallmark in severe diseases such as atherosclerosis and non-alcohol-induced steatohepatitis (NASH). In the development of inflammation, prostaglandins, especially prostaglandin E

The metrological structural resolution (MSR) describes the size of the smallest surface feature that can be measured dimensionally with a given accuracy. Several methods to determine the MSR for dimensional x-ray CT (dXCT) have been proposed in the past, two of which are compared and related in this publication, i.e. the curved-edge based (CEB) and the profile-based spectral (PBS) method. Both methods consider the surface structure as being described by a single surface on the relevant local scale and are also suitable for the application to optical or tactile coordinate measurement systems (CMSs). The CEB method evaluates the radii of circular shapes to determine the width of the Gaussian filter that describes the filtering of the surface by the CMS. The PBS method evaluates the instrument transfer function (ITF) determined by means of the measurement of a surface profile with a broad-band spatial frequency spectrum with a finite cut-off frequency. The PBS method yields the threshold wavelength for which the amplitude of the ITF drops below a certain level. While the resulting quantities of the two methods are very different they evaluate the same characteristic of the CMS. In this publication an analytical relation between those results is derived and shown to exist which is used to define the MSR. Simulated CT scans as well as dXCT measurements are performed to verify this relation. The results for the MSR obtained from both methods are consistent and deviations to the expectations based on theory are within a reasonable range.

Das Thema Elektromobilität in der Landwirtschaft gewinnt zunehmend an Relevanz, was sich beispielsweise in der Entwicklung erster elektrisch betriebener Traktorenkonzepte manifestiert. Ob sich diese Konzepte allerdings in der Breite etablieren lassen oder als Nische verbleiben, ist noch unklar. Fakt ist, dass die Akzeptanz der E-Mobilität unter Landwirten hierbei künftige eine entscheidende Rolle spielen wird. Über die ex-ante Nutzerakzeptanz elektrisch betriebener Landmaschinen ist, verglichen mit dem Automobilsektor, jedoch noch wenig bekannt. Daher werden in dieser explorativen Studie die Einflussfaktoren der ex-ante Nutzerakzeptanz elektrisch betriebener Landmaschinen qualitativ untersucht, um so einen Beitrag zur weiteren Erforschung der Nutzerakzeptanz zu leisten. Mithilfe qualitativer Experteninterviews wurden 15 Betriebsleiter unterschiedlich organisierter Landwirtschaftsbetriebe zu diesem Thema befragt. Die Ergebnisse verdeutlichen einerseits, dass unter den 15 befragten Landwirten mehrheitlich kritische Positionen bezüglich der Verbreitung und des Einsatzes von Elektromobilität in der Landwirtschaft vorherrschen. Andererseits zeigte sich, dass die ex-ante Nutzerakzeptanz elektrisch betriebener Landmaschinen nicht nur von unterschiedlichen Faktoren beeinflusst wird, sondern dass diese auch untereinander verknüpft und somit teilwiese indirekt auf die ex-ante Nutzerakzeptanz der Befragten wirken.

WA : 0853-1102-5193. Daftar Harga Jual Tempat Pemandian Jenazah Siempat Rube. Terbukti AWET. Bahan Berkualitas. Full Stainless Steel. Anti Karat . Bisa menahan beban hingga 300 kg Bahan : Full Stainless Steel . KELEBIHAN BELANJA DI KAMI 1. Anti karat 2. Terbukti Awet Bertahun tahun 3. Full Stainless Steel 4. Bahan Berkualitas 5. BERGARANSI . Order Hubungi : WA 0853 1102 5193 https://wa.me/6285311025193 Web Official : Https://PabrikKeranda.co.id . Pabrik Tempat Pemandian Jenazah Siempat Rube, Tempat Pemandian Mayat Stainless Siempat Rube, Ukuran tempat pemandian jenazah Siempat Rube, Tempat Memandikan Jenazah Siempat Rube, Tempat Memandikan Jenazah Stainless Siempat Rube, Tempat Pemandian Mayat Stainless Siempat Rube, Jual Tempat Pemandian Jenazah Siempat Rube, ukuran tempat memandikan jenazah Siempat Rube, tempat memandikan jenazah menurut islam Siempat Rube, tempat pemandian jenazah dari stainless Siempat Rube, Tempat Memandikan Mayat Siempat Rube, Tempat Pemandian Jenazah Siempat Rube, Tempat Untuk Memandikan Mayat Siempat Rube, Pemandian Mayat Siempat Rube, Tempat Mandi Mayat Stainless Siempat Rube, Tempat Mandi Jenazah Siempat Rube, Tempat Mandi Jenazah Stainless Steel Siempat Rube, Jual Tempat Mandi Jenazah Siempat Rube, Tempat Pemandian Mayat Siempat Rube, Tempat Memandikan Jenazah Siempat Rube Siempat Rube, Tempat Untuk Memandikan Jenazah Siempat Rube, Jual Tempat Memandikan Jenazah Siempat Rube, Pemandian Mayat Stainless Siempat Rube, Pemandian Mayat Stenlis Siempat Rube, Tempat Mandi Mayat Siempat Rube, bak pemandian jenazah Siempat Rube, bak pemandian mayat Siempat Rube, bak untuk memandikan jenazah Siempat Rube, gambar tempat memandikan jenazah Siempat Rube, harga tempat memandikan jenazah stainless Siempat Rube, berapa harga tempat pemandian jenazah Siempat Rube, daftar harga tempat pemandian jenazah Siempat Rube, harga tempa memandikan jenazah Siempat Rube, tempat pemandian jenazah sesuai ppi Siempat Rube

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Designing visual models to describe and conceptualize objects and systems requires abstraction skills and a predisposition for visual interactions. Readily available modeling tools rely on the users’ logical-mathematical and visual-spatial abilities to support modeling design. However, they fall short of mechanisms to tap into the users’ bodily-kinesthetic abilities. This research presents a model-driven framework to automatically develop visual editors to work with Domain Specific Languages in tangible interaction environments. The framework is illustrated through the development of an editor of entity-relationship models supported by augmented reality. The editor usability evaluation indicates good acceptance by users as well as potential to support alternative interactions and to learn database concepts.

CRISPR RNA-guided endonucleases (RGEs) cut or direct activities to specific genomic loci, yet each has off-target activities that are often unpredictable. We developed a pair of simple in vitro assays to systematically measure the DNA-binding specificity (Spec-seq), catalytic activity specificity (SEAM-seq) and cleavage efficiency of RGEs. By separately quantifying binding and cleavage specificity, Spec/SEAM-seq provides detailed mechanistic insight into off-target activity. Feature-based models generated from Spec/SEAM-seq data for SpCas9 were consistent with previous reports of its in vitro and in vivo specificity, validating the approach. Spec/SEAM-seq is also useful for profiling less-well characterized RGEs. Application to an engineered SpCas9, HiFi-SpCas9, indicated that its enhanced target discrimination can be attributed to cleavage rather than binding specificity. The ortholog ScCas9, on the other hand, derives specificity from binding to an extended PAM. The decreased off-target activity of AsCas12a (Cpf1) appears to be primarily driven by DNA-binding specificity. Finally, we performed the first characterization of CasX specificity, revealing an all-or-nothing mechanism where mismatches can be bound, but not cleaved. Together, these applications establish Spec/SEAM-seq as an accessible method to rapidly and reliably evaluate the specificity of RGEs, Cas::gRNA pairs, and gain insight into the mechanism and thermodynamics of target discrimination.

In eukaryotes, members of large transcription factor families often exhibit similar DNA binding properties in vitro, yet initiate paralog-specific gene regulatory networks in vivo. The serially homologous first (T1) and third (T3) thoracic legs of Drosophila, which result from alternative gene regulatory networks specified by the Hox proteins Scr and Ubx, respectively, offer a unique opportunity to address this paradox in vivo. Genome-wide analyses using epitope-tagged alleles of both Hox loci in the T1 and T3 leg imaginal discs, which are the precursors to the adult appendages and ventral body regions, show that ∼8% of Hox binding is paralog-specific. Binding specificity is mediated by interactions with distinct cofactors in different domains: the known Hox cofactor Exd acts in the proximal domain and is necessary for Scr to bind many of its paralog-specific targets, while in the distal leg domain, we identified the homeodomain protein Distal-less (Dll) as a novel Hox cofactor that enhances Scr binding to a different subset of genomic loci. Reporter genes confirm the in vivo roles of Scr+Dll and suggest that ∼1/3 of paralog-specific Hox binding in enhancers is functional. Together, these findings provide a genome-wide view of how Hox paralogs, and perhaps paralogs of other transcription factor families, orchestrate alternative downstream gene networks and suggest the importance of multiple, context-specific cofactors.

JMIR medical education 8(2), e34042 (2022). doi:10.2196/34042, Published by JMIR Publications, Toronto

BACKGROUND The digital age has introduced opportunities and challenges for clinical education and practice caused by infinite incoming information and novel technologies for health. In the interdisciplinary field of communication sciences and disorders (CSD), engagement with digital topics has emerged slower than in other health fields, and effective strategies for accessing, managing, and focusing on digital resources are greatly needed. OBJECTIVE We aimed to conceptualize and investigate preferences of stakeholders regarding a digital learning toolbox, an app containing a library of current resources for CSD. This cross-sectional survey study conducted in German-speaking countries investigated professional and student perceptions and preferences regarding such an app’s features, functions, content, and associated concerns. METHODS An open web-based survey was disseminated to professionals and students in the field of CSD, including speech-language pathologists (SLPs; German: Logopäd*innen), speech-language pathology students, phoniatricians, otolaryngologists, and medical students. Insights into preferences and perceptions across professions, generations, and years of experience regarding a proposed app were investigated. RESULTS Of the 164 participants, an overwhelming majority (n=162, 98.8%) indicated readiness to use such an app, and most participants (n=159, 96.9%) perceived the proposed app to be helpful. Participants positively rated app functions that would increase utility (eg, tutorial, quality rating function, filters based on content or topic, and digital format); however, they had varied opinions regarding an app community feature. Regarding app settings, most participants rated the option to share digital resources through social media links (144/164, 87.8%), receive and manage push notifications (130/164, 79.3%), and report technical issues (160/164, 97.6%) positively. However, significant variance was noted across professions (H3=8.006; P=.046) and generations (H3=9.309; P=.03) regarding a username-password function, with SLPs indicating greater perceived usefulness in comparison to speech-language pathology students (P=.045), as was demonstrated by Generation X versus Generation Z (P=.04). Participants perceived a range of clinical topics to be important; however, significant variance was observed across professions, between physicians and SLPs regarding the topic of diagnostics (H3=9.098; P=.03) and therapy (H3=21.236; P CONCLUSIONS This investigation demonstrated that professionals and students show initial readiness to engage in the co-design and use of an interdisciplinary digital learning toolbox app. Specifically, this app could support effective access, sharing, evaluation, and knowledge management in a digital age of rapid change. Formalized digital skills education in the field of CSD is just a part of the solution. It will be crucial to explore flexible, adaptive strategies collaboratively for managing digital resources and tools to optimize targeted selection and use of relevant, high-quality evidence in a world of bewildering data.

In 2009 Pranav Mistry presented the Sixth Sense project, which used Spatial Augmented Reality to display information directly on the user’s environment using a projector. The user interacts with the virtual elements without the need to use typical interfaces such as screens or keyboards. At present, different projects make use of Virtual Reality in serious games as a mechanism for the rehabilitation of patients. This research presents an update of the Sixth Sense project to study the possibilities offered by Augmented Reality as a mechanism for the rehabilitation of patients with neurological diseases by the Linguistics Area of the University of Cadiz.

Objective: To study the effect of obesity on retinal structures in African Americans (AAs) and Caucasian Americans (CAs) with relapsing-remitting multiple sclerosis (RRMS).Methodology: About 136 patients with RRMS without history of optic neuritis were divided into two groups, based on body mass index (BMI): 67 obese (40 AA, 27 CA, mean BMI ± SD: 36.7 ± 5.8), and 69 non-obese (23 AA, 46 CA, mean BMI ± SD: 24.0 ± 3.1). The peripapillary retinal nerve fiber layer (pRNFL) thickness was quantified by optical coherence tomography (OCT) and was segmented into quadrant thickness: superior (S), inferior (I), temporal (T), and nasal (N). Papillomacular bundle (PMB) thickness, retinal nerve fiber layer (RNFL), ganglion cell + inner plexiform layer (GCIPL), inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL), and total macular (TMV) volumes were obtained.Results: Obesity was associated with lower T thickness (58.54 ± 15.2 vs. 61.9 12.4, p = 0.044), higher INL (0.98 ± 0.07 vs. 0.96 ± 0.06, p = 0.034), and lower RNFL (0.77 ± 0.14 vs. 0.82 ± 0.12, p = 0.009) volumes. Obese AA had significantly thinner T (58.54 ± 15.19 vs. 61.91 ± 12.39, p = 0.033), N (68.94 ± 2.7 vs. 77.94 ± 3.3, p = 0.044), and TMV (8.15 ± 0.07 vs. 8.52 ± 0.09, p = 0.003), RNFL (0.74 ± 0.02 vs. 0.82 ± 0.02, p = 0.013), OPL (0.76 ± 0.01 vs. 0.79 ± 0.1, p = 0.050), ONL (1.68 ± 0.031 vs. 1.79 ± 0.038, p = 0.026), and GCIPL (1.78 ± 0.04 vs. 1.9 ± 0.05, p = 0.038) compared to obese CA. Among patients with non-obesity, the ONL was significantly lower in AA (1.78 ± 0.04 vs. 1.9 ± 0.05, p < 0.001).Conclusions: Obesity is associated with retinal structure abnormalities in patients with RRMS. Its impact might be more prominent in AA than CA. Large longitudinal studies are needed to validate our findings.

Quantifying sequence-specific protein-ligand interactions is critical for understanding and exploiting numerous cellular processes, including gene regulation and signal transduction. Next-generation sequencing (NGS) based assays are increasingly being used to profile these interactions with high-throughput. However, these assays do not provide the biophysical parameters that have long been used to uncover the quantitative rules underlying sequence recognition. We developed a highly flexible machine learning framework, called ProBound, to define sequence recognition in terms of biophysical parameters based on NGS data. ProBound quantifies transcription factor (TF) behavior with models that accurately predict binding affinity over a range exceeding that of previous resources, captures the impact of DNA modifications and conformational flexibility of multi-TF complexes, and infers specificity directly from in vivo data such as ChIP-seq without peak calling. When coupled with a new assay called Kd-seq, it determines the absolute affinity of protein-ligand interactions. It can also profile the kinetics of kinase-substrate interactions. By constructing a biophysically robust foundation for profiling sequence recognition, ProBound opens up new avenues for decoding biological networks and rationally engineering protein-ligand interactions.

Neural plasticity 2019, 1-21 (2019). doi:10.1155/2019/9603469, Published by Hindawi, New York, NY

The use of code quality control platforms for analysing source code is increasingly gaining attention in the developer community. These platforms are prepared to parse and check source code written in a variety of general-purpose programming languages. The emergence of domain-specific languages enables professionals from different areas to develop and describe problem solutions in their disciplines. Thus, source code quality analysis methods and tools can also be applied to software artefacts developed with a domain-specific language. To evaluate the quality of domain-specific language code, every software component required by the quality platform to parse and query the source code must be developed. This becomes a time-consuming and error-prone task, for which this paper describes a model-driven interoperability strategy that bridges the gap between the grammar formats of source code quality parsers and domain-specific text languages. This approach has been tested on the most widespread platforms for designing text-based languages and source code analysis. This interoperability approach has been evaluated on a number of specific contexts in different domain areas.

A visual programming language allows users and developers to create programs by manipulating program elements graphically. Several studies have shown the bene ts of visual languages for learning purposes and their applicability to robot programming. However, at present, there are not enough comparative studies on the suitability of textual and visual languages for this purpose. In this paper, we study if, as with a textual language, the use of a visual language could also be suitable in the context of robot programming and, if so, what the main advantages of using a visual language would be. For our experiments, we selected a sample of 60 individuals among students with adequate knowledge of procedural programming, that was divided into three groups. For the rst group of 20 students, a learning scenario based on a textual objectoriented language was used for programming a speci c commercial robotic ball with sensing, wireless communication, and output capabilities, whereas for the second and the third group, two learning scenarios based on visual languages were used for programming the robot. After taking a course for programming the robot in the corresponding learning scenario, each group was evaluated by completing three programming exercises related to the robot features (i.e. motion, lighting, and collision detection). Our results show that the students that worked with visual languages perceived a higher clarity level in their understanding of the course exposition, and a higher enjoyment level in the use of the programming environment. Moreover, they also achieved an overall better mark. Agencia Española de Investigación (AEI) TIN2017-85797-R

Background Clinical interface terminologies (CITs) consist of terms designed for clinical documentation and, through mappings to standardized vocabularies, to support secondary uses of patient data, including clinical decision support, quality measurement, and billing for health care services. The latter purpose requires maps to administrative coding systems, such as the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), for diagnoses in the United States. Objectives The transition from ICD-9-CM to ICD-10-CM posed a challenge to CIT users due to the substantially increased details in ICD-10-CM. To address this, we developed a content layer within a CIT that provides postcoordination prompts for the details required for accurate ICD-10-CM coding. Methods We developed content to support prompting for and capture of additional information specified by the user in a single, clinically relevant term that is added to the patient's record, and whose mapping to other coding systems (like Systematized Nomenclature of Medicine—Clinical Terms [SNOMED CT]) reflects the details added during postcoordination. We worked with clinical information system developers to incorporate this into user interfaces, and with end-users to refine the design. Results While the prompts were designed around the precoordinated elements implicit in ICD-10-CM, irregularities in ICD-10-CM required some additional design measures, such as providing postcoordination options that interpolate gaps in ICD-10-CM to avoid user confusion. The system we describe has been implemented by ∼30,000 health care provider organizations, with content that covers the vast majority of encounter diagnoses. User feedback has been largely positive, though concerns have been raised about expanding postcoordination content beyond that required for ICD-10-CM coding. Conclusion We have demonstrated the design and development of what, to our knowledge, is the first system that uses postcoordination to capture ICD-10-CM-relevant details in a CIT while also reflecting the details added by the user in maps to other vocabularies.

X-ray computed tomography (XCT) is a fast-growing technology for dimensional measurements in industrial applications. However, traceable and efficient methods to determine measurement uncertainties are not available. Guidelines like the VDI/VDE 2630 Part 2.1 suggest at least 20 repetitions of a specific measurement task, which is not feasible for industrial standards. Simulation-based approaches to determine task specific measurement uncertainties are promising, but require closely adjusted model parameters and an integration of error sources like geometrical deviations during a measurement. Unfortunately, the development of an automated process to parameterize and integrate geometrical deviations into XCT models is still an open issue. In this work, the whole processing chain of dimensional XCT measurements is taken into account with focus on the issues and requirements to determine suitable parameters of geometrical deviations. Starting off with baseline simulations of different XCT systems, two approaches are investigated to determine and integrate geometrical deviations of reference measurements. The first approach tries to iteratively estimate geometric deviation parameter values to match the characteristics of the missing error sources. The second approach estimates those values based on radiographs of a known calibrated reference object. In contrast to prior work both approaches only use a condensed set of parameters to map geometric deviations. In case of the iterative approach, some major issues regarding unhandled directional dependencies have been identified and discussed. Whereas the radiographic method resulted in task specific expanded measurements uncertainties below one micrometre even for bi-directional features, which is a step closer towards a true digital twin for uncertainty estimations in dimensional XCT.

Protein-ligand interactions are increasingly profiled at high throughput using affinity selection and massively parallel sequencing. However, these assays do not provide the biophysical parameters that most rigorously quantify molecular interactions. Here we describe a flexible machine learning method, called ProBound, that accurately defines sequence recognition in terms of equilibrium binding constants or kinetic rates. This is achieved using a multi-layered maximum-likelihood framework that models both the molecular interactions and the data generation process. We show that ProBound quantifies transcription factor (TF) behavior with models that predict binding affinity over a range exceeding that of previous resources; captures the impact of DNA modifications and conformational flexibility of multi-TF complexes; and infers specificity directly from in vivo data such as ChIP-seq without peak calling. When coupled with an assay called KsubD/sub-seq, it determines the absolute affinity of protein-ligand interactions. We also apply ProBound to profile the kinetics of kinase-substrate interactions. ProBound opens new avenues for decoding biological networks and rationally engineering protein-ligand interactions.

BACKGROUND Advances in digital health and digital learning are transforming the lives of patients, health care providers, and health professional students. In the interdisciplinary field of communication sciences and disorders (CSD), digital uptake and incorporation of digital topics and technologies into clinical training programs has lagged behind other medical fields. There is a need to understand professional and student experiences, opinions, and needs regarding digital health and learning topics so that effective strategies for implementation can be optimized. OBJECTIVE This cross-sectional survey study aims to interdisciplinarily investigate professional and student knowledge, use, attitudes, and preferences toward digital health and learning in the German-speaking population. METHODS An open-ended, web-based survey was developed and conducted with professionals and students in CSD including phoniatricians and otolaryngologists, speech-language pathologists (German: Logopäd*innen), medical students, and speech-language pathology students. Differences in knowledge, use, attitudes, and preferences across profession, generation, and years of experience were analyzed. RESULTS A total of 170 participants completed the survey. Respondents demonstrated greater familiarity with digital learning as opposed to eHealth concepts. Significant differences were noted across profession (P<.001), generation (P=.001), and years of experience (P<.001), which demonstrated that students and younger participants were less familiar with digital health terminology. Professional (P<.001) and generational differences were also found (P=.04) in knowledge of digital therapy tools, though no significant differences were found for digital learning tools. Participants primarily used computers, tablets, and mobile phones; non–eHealth-specific tools (eg, word processing and videoconferencing applications); and digital formats such as videos, web courses, and apps. Many indicated a desire for more interactive platforms, such as virtual reality. Significant differences were found across generations for positive views toward digitalization (P<.001) and across profession for feelings of preparedness (P=.04). Interestingly, across profession (P=.03), generation (P=.006), and years of experience (P=.01), students and younger participants demonstrated greater support for medical certification. Commonly reported areas of concern included technical difficulties, quality and validity of digital materials, data privacy, and social presence. Respondents tended to prefer blended learning, a limited to moderate level of interactivity, and time and space–flexible learning environments (63/170, 37.1%), with a notable proportion still preferring traditional time and space–dependent learning (49/170, 28.8%). CONCLUSIONS This comprehensive investigation into the current state of CSD student and professional opinions and experiences has shown that incorporation of digital topics and skills into academic and professional development curricula will be crucial for ensuring that the field is prepared for the ever-digitalizing health care environment. Deeper empirical investigation into efficacy and acceptance of digital learning and practice strategies and systematic training and practical organizational supports must be planned to ensure adaptive education and practice. CLINICALTRIAL

BACKGROUND The digital revolution is rapidly transforming health care and clinical teaching and learning. Relative to other medical fields, the interdisciplinary fields of speech-language pathology (SLP), phoniatrics, and otolaryngology have been slower to take up digital tools for therapeutic, teaching, and learning purposes—a process that was recently expedited by the COVID-19 pandemic. Although many current teaching and learning tools have restricted or institution-only access, there are many openly accessible tools that have gone largely unexplored. To find, use, and evaluate such resources, it is important to be familiar with the structures, concepts, and formats of existing digital tools. OBJECTIVE This descriptive study aims to investigate digital learning tools and resources in SLP, phoniatrics, and otolaryngology. Differences in content, learning goals, and digital formats between academic-level learners and clinical-professional learners are explored. METHODS A systematic search of generic and academic search engines (eg, Google and PubMed); the App Store; Google Play Store; and websites of established SLP, phoniatrics, and otolaryngology organizations was conducted. By using specific search terms and detailed inclusion and exclusion criteria, relevant digital resources were identified. These were organized and analyzed according to learner groups, content matter, learning goals and architectures, and digital formats. RESULTS Within- and between-learner group differences among 125 identified tools were investigated. In terms of content, the largest proportion of tools for academic-level learners pertained to anatomy and physiology (60/214, 28%), and that for clinical-professional learners pertained to diagnostic evaluation (47/185, 25.4%). Between groups, the largest differences were observed for anatomy and physiology (academic-level learners: 60/86, 70%; clinical-professional learners: 26/86, 30%) and professional issues (8/28, 29% vs 20/28, 71%). With regard to learning goals, most tools for academic-level learners targeted the performance of procedural skills (50/98, 51%), and those for clinical-professional learners targeted receptive information acquisition (44/62, 71%). Academic-level learners had more tools for supporting higher-level learning goals than clinical-professional learners, specifically tools for performing procedural skills (50/66, 76% vs 16/66, 24%) and strategic skills (8/10, 80% vs 2/10, 20%). Visual formats (eg, pictures or diagrams) were dominant across both learner groups. The greatest between-group differences were observed for interactive formats (45/66, 68% vs 21/66, 32%). CONCLUSIONS This investigation provides initial insights into openly accessible tools across SLP, phoniatrics, and otolaryngology and their organizing structures. Digital tools in these fields addressed diverse content, although the tools for academic-level learners were greater in number, targeted higher-level learning goals, and had more interactive formats than those for clinical-professional learners. The crucial next steps include investigating the actual use of such tools in practice and students’ and professionals’ attitudes to better improve upon such tools and incorporate them into current and future learning milieus.

BACKGROUND Numerous publications show that electronic medical records (EMRs) may make an important contribution to increasing the quality of care. There are indications that particularly the medical specialist plays an important role in the use of EMRs in hospitals. OBJECTIVE The aim of this study was to examine how, and by which aspects, the relationship between EMR use and the quality of care in hospitals is influenced according to medical specialists. METHODS To answer this question, a qualitative study was conducted in the period of August-October 2018. Semistructured interviews of around 90 min were conducted with 11 medical specialists from 11 different Dutch hospitals. For analysis of the answers, we used a previously published taxonomy of factors that can influence the use of EMRs. RESULTS The professional experience of the participating medical specialists varied between 5 and 27 years. Using the previously published taxonomy, these medical specialists considered technical barriers the most significant for EMR use. The suboptimal change processes surrounding implementation were also perceived as a major barrier. A final major problem is related to the categories “social” (their relationships with the patients and fellow care providers), “psychological” (based on their personal issues, knowledge, and perceptions), and “time” (the time required to select, implement, and learn how to use EMR systems and subsequently enter data into the system). However, the medical specialists also identified potential technical facilitators, particularly in the assured availability of information to all health care professionals involved in the care of a patient. They see promise in using EMRs for medical decision support to improve the quality of care but consider these possibilities currently lacking. CONCLUSIONS The 11 medical specialists shared positive experiences with EMR use when comparing it to formerly used paper records. The fact that involved health care professionals can access patient data at any time they need is considered important. However, in practice, potential quality improvement lags as long as decision support cannot be applied because of the lack of a fully coded patient record.

Stadtentwicklungsprozesse stehen aktuell haufig durch Widerspruche und Burgerproteste unter Druck. Je nach Beteiligungsprozess entstehen sowohl auf individueller wie auch auf gemeinschaftlicher Ebene Lernerfahrungen, die die Partizipationskultur des Kollektivs nachhaltig pragen.

Systematic reviews are powerful methods used to determine the state-of-the-art in a given field from existing studies and literature. They are critical but time-consuming in research and decision making for various disciplines. When conducting a review, a large volume of data is usually generated from relevant studies. Computer-based tools are often used to manage such data and to support the systematic review process. This paper describes a comprehensive analysis to gather the required features of a systematic review tool, in order to support the complete evidence synthesis process. We propose a framework, elaborated by consulting experts in different knowledge areas, to evaluate significant features and thus reinforce existing tool capabilities. The framework will be used to enhance the currently available functionality of CloudSERA, a cloud-based systematic review tool focused on Computer Science, to implement evidence-based systematic review processes in other disciplines., This research was funded by the Spanish Research Agency (Agencia Estatal de Investigacion) with ERDF funds grant number TIN2017-85797-R (VISAIGLE project). The research stay of T. Person in the SFU was funded by Erasmus+ KA107 grant number 2017-1-ES01-KA107-037422. The APC was funded by the VISAIGLE project.

Mechanical deformations of DNA such as bending are ubiquitous and have been implicated in diverse cellular functions1. However, the lack of high-throughput tools to measure the mechanical properties of DNA has limited our understanding of how DNA mechanics influence chromatin transactions across the genome. Here we develop 'loop-seq'-a high-throughput assay to measure the propensity for DNA looping-and determine the intrinsic cyclizabilities of 270,806 50-base-pair DNA fragments that span Saccharomyces cerevisiae chromosome V, other genomic regions, and random sequences. We found sequence-encoded regions of unusually low bendability within nucleosome-depleted regions upstream of transcription start sites (TSSs). Low bendability of linker DNA inhibits nucleosome sliding into the linker by the chromatin remodeller INO80, which explains how INO80 can define nucleosome-depleted regions in the absence of other factors2. Chromosome-wide, nucleosomes were characterized by high DNA bendability near dyads and low bendability near linkers. This contrast increases for deeper gene-body nucleosomes but disappears after random substitution of synonymous codons, which suggests that the evolution of codon choice has been influenced by DNA mechanics around gene-body nucleosomes. Furthermore, we show that local DNA mechanics affect transcription through TSS-proximal nucleosomes. Overall, this genome-scale map of DNA mechanics indicates a 'mechanical code' with broad functional implications.