bluuebunny/crossref_metadata_2025 huggingface dataset:
CROWBAR: Natively Fuzzing Trusted Applications Using ARM CoreSight
Authors: Shan Haoqi , Huang Moyao , Liu Yujia , Nissankararao Sravani , Jin Yier , Wang Shuo , Sullivan Dean
Published: June 2023

Trusted execution environments (TEE) are deployed on many platforms to provide both confidentiality and integrity, and their extensive use offers a secure environment for privacy-sensitive operations. Despite TEE prevalence in the smartphone and tablet market, vulnerability research into TEE security is relatively rare. This is, in part, due to the strong isolation guarantees provided by its implementation. In this paper, we propose a hardware assisted fuzzing framework, CROWBAR, that bypasses TEE isolation to natively evaluate trusted applications (TAs) on mobile devices by leveraging ARM CoreSight components. CROWBAR performs feedback-driven fuzzing on commercial, closed source TAs while running in a TEE protected environment. We implement CROWBAR on 2 prototype commercial-off-the-shelf (COTS) smartphones and one development board, finding 3 unique crashes in 5 closed source TAs that are previously unreported in the TrustZone fuzzing literature.
Feasibility study on a large scale 3D printed scissor structure
Authors: Guillén Juan Francisco García , Kungurova Stanislava , Lim Hui Jie , Shchukina Alisa , Ng Ji Yann , Reich Stefan , Buchmann Carl
Published: June 2023

This paper presents a case study on applying large-scale additive manufacturing (LSAM) to scissor-type deployable structures for disaster shelters. The use of advanced technology has become increasingly popular among architects, engineers, and other stakeholders looking to achieve more efficient designs. In this context, LSAM offers the potential to optimize form, reduce material consumption, and speed up the construction process. The project includes both a theoretical study of scissor structures and practical feasibility tests, culminating in the design and manufacture of a full-scale printed prototype. Computational design tools were used to analyze and compare different designs and simulate manufacturing processes in a virtual environment. Through this case study, we provide a detailed account of our journey from design to fabrication and offer a critical reflection on the findings.
Metastasiertes Urothelkarzinom – Spätlinientherapien
Authors: Krauter Johanna , Gust Kilian , Shariat Shahrokh
Published: June 2023

Das fortgeschrittene/metastasierte Urothelkarzinom ist eine aggressive Erkrankung mit daraus resultierender begrenzter Lebenserwartung der Patienten. Die bisherige Standardtherapie beschränkte sich lange Zeit auf eine platinbasierte Chemotherapie in der Erstlinie. In den letzten Jahren hielt die Immuntherapie Einzug in die Therapie des mUC: in der Erstlinie bei Platin-ungeeigneten Patienten, in der Erhaltung nach Nichtprogress unter Erstlinienchemotherapie sowie in der Zweitlinientherapie. Avelumab ist mittlerweile der Standard als Erhaltungstherapie nach Ansprechen oder stabilem Befund nach der Chemotherapie. Sollte es während oder nach der platinbasierten Erstlinienchemotherapie zum Progress kommen, wird Pembrolizumab in allen Leitlinien unabhängig vom „Programmed cell death-ligand 1“(PD-L1)-Status in der Zweitlinie empfohlen. Eine weitere Möglichkeit ist nachfolgend die erneute Chemotherapie mit Vinflunin, Taxanen oder eine Re-Challenge mit platinbasierter Chemotherapie, wobei die Erfolge dieses Vorgehens nicht zufriedenstellend sind. In den letzten Jahren wurden für dieses Setting einige neue Therapien entwickelt. In den NCCN- und ESMO-Leitlinien werden Antikörper-Wirkstoff-Konjugate (AWK) wie Enfortumab-Vedotin oder der Pan-FGFR-Tyrosinkinase-Inhibitor (FGFR: Fibroblastenwachstumsfaktorenrezeptor) Erdafitinib bei FGFR2-/3-Alterationen als Drittlinientherapie bereits diskutiert. In Europa ist derzeit nur Enfortumab-Vedotin von der EMA bei Progress nach Chemo- und Immuntherapie zugelassen. Die Zulassung von Erdafitinib steht derzeit noch aus. Eine weitere neue Option ist Sacituzumab-Govitecan (Trop-2), hier steht die Zulassung durch die EMA ebenso aus. Weitere molekulargenetische Ansatzpunkte können etwaig durch „next generation sequencing“ (NGS) aufgezeigt werden und machen so in spezialisierten Zentren ggf. weitere Therapien auch nach Ausschöpfen der Standardtherapien möglich. Grundvorrausetzung für die optimale Versorgung des Patienten ist die Behandlung in einem erfahrenen Zentrum, um die bestmögliche Strategie für den Patienten, v. a. in späteren Therapielinien, zu gewährleisten und den Einschluss in weiterführende Studien zu ermöglichen.
A theoretical liquid crystal elastomer model that mimics the elasticity of cat skin
Authors: Mihai L. Angela
Published: June 2023

A mathematical model for nematic liquid crystal elastomers is proposed that mimics the elastic response of cat skin where reorientation of dermal fibres produces an increase in the thickness direction under tensile stretch. To capture this unusual effect, the uniaxial order parameter in the nematic elastomer model is allowed to decrease then increase again, and the critical stretch at which this change of monotonicity occurs and where the director also rotates suddenly is predicted. In addition, the model parameters are described by probability density functions and their uncertainty is propagated numerically to the predicted mechanical results.
Agro-ecological intensification for climate change adaptation: tales on soil and water management practices of smallholder farmers in rural Ghana
Authors: Naazie Godwin K. , Dakyaga Francis , Derbile Emmanuel K.
Published: June 2023

In response to the increasing impacts of climatic stressors on human populations, climatic scholars have emphasized the need for alternative approaches to adapt food crop production to climate change and sustain the livelihoods of smallholder farmers. Inspired by agro-ecological intensification (AEI) practices of smallholder farmers, this study contributes to climate change adaptation debates in Sub-Saharan Africa by providing a context-specific exploration of everyday traditional soil and water management practices employed by smallholder farmers in adapting food crop production to climate change. The study employed a qualitative research design, conducted household case studies, focus group discussions, key informant interviews, and a review of secondary data. We show that smallholder farmers employ diverse range of agronomic practices, with a particular emphasis on traditional soil and water management techniques. Such as the preparation and application of organic manure and compost, ridges formation, crop rotation, and cover cropping. These agronomic practices were complemented by the application of limited inorganic fertilizers and applied across different types of farms; compound and bush farms, valley fields, and gardens to adapt production to climate change. We argue that smallholder farmers are more inclined towards adopting AEI as a means of climate change adaptation due to their strong reliance on traditional farming methods, that draws heavily on local resources, indigenous knowledge as relatively affordable practices. Therefore, we emphasize the importance of incorporating an Endogenous Development (ED) approach in promoting AEI as part of climate change adaptation planning, particularly in rural Ghana and other Sub-Saharan African regions facing similar conditions.
To democratize or not to democratize AI? That is the question
Authors: Murphy John W. , Taylor Randon R.
Published: June 2023

This paper advances the debate surrounding whether to democratize AI and explores some of the challenges and benefits of democratization through community-based work and direct democracy. We contend that community-based strategies can incorporate local knowledge and control, thereby providing more effective AI solutions that are human-centric and less harmful. However, democratization needs to be approached with caution and care, since this process requires a deeper understanding of who participates, the decision domain, and the different realities at stake. Moreover, we highlight the importance of participation in AI development to ensure its legitimacy, considering the capacity of this technology to shape reality. We emphasize that participation should be more than just involving stakeholders or seeking input from users. Rather, participation should involve local narratives that generate knowledge and shape information landscapes, thereby producing a different, anti-Cartesian scene. We conclude by underscoring that the success of democratizing AI hinges on the careful delineation of the boundaries of participation, which should include the specific needs of the immediate context, the decision domain, and the various participants involved.
Achieving sustainable development goals through digitalising creative works: some evidence from social enterprises in Indonesia
Authors: Pratono Aluisius Hery , Nawangpalupi Catharina Badra , Sutanti Ari
Published: June 2023

This article aims to examine how businesses support the SDGs by exploring the role of social enterprises in supporting creative workers by adopting digital economic activities. This study adopts the inductive qualitative approach by observing the creative industry, conducting focus group discussions, and interviewing the main stakeholders to arrive at four findings. The findings indicate that social enterprises (1) encourage the creative workers to embrace their cultural identities by providing a digital platform, (2) support the creative workers to deal with customers by exploiting resourceful social networks, (3) promote inclusive community governance by adopting the crowdfunding platform, and (4) help the creative workers gain support from donors by showing their excellent pilot projects. The article extends the debate between neoclassical economics with profit-oriented goals and social enterprise approaches by highlighting the role of stakeholder, triple bottom line, and identity theories.
Reverse-engineering information presentations: recovering hierarchical grouping from layouts of visual elements
Authors: Shi Danqing , Cui Weiwei , Huang Danqing , Zhang Haidong , Cao Nan
Published: June 2023

Visual elements in an information presentation are often spatially and semantically grouped hierarchically for effective message delivery. Studying the hierarchical grouping information can help researchers and designers better explore layout structures and understand design demographics. However, recovering hierarchical grouping is challenging due to a large number of possibilities for compositing visual elements into a single-page design. This paper introduces an automatic approach that takes the layout of visual elements as input and returns the hierarchical grouping as output. To understand information presentations, we first contribute a dataset of 23,072 information presentations with diverse layouts to the community. Next, we propose our technique with a Transformer-based model to predict relatedness between visual elements and a bottom-up algorithm to produce the hierarchical grouping. Finally, we evaluate our technique through a technical experiment and a user study with 30 designers. The results show that the proposed technique is promising.
Matter and Making in Early English Poetry
Authors: Cowdery Taylor
Published: June 2023

What is literature made from? During the fourteenth, fifteenth, and sixteenth centuries, this question fascinated English court poets, who often claimed that their poems were not original creations, but adaptations of pre-existing materials. Their word for these materials was 'matter,' while the term they used to describe their labor was 'making,' or the act of reworking this matter into a new – but not entirely new – form. By tracing these ideas through the work of six major early poets, this book offers a revisionist literary history of early court poetry. It reconstructs their theories of making and contrasts them with more modern theories of literary labor, such as 'authorship.' It studies the textual, historical, and philosophical sources that these poets used as matter. Most of all, it demonstrates that early court poets drew attention to their source materials for aesthetic reasons, and not because of any lapse in technique.
The Full Armor of God
Authors: Djupe Paul A. , Lewis Andrew R. , Sokhey Anand E.
Published: June 2023

Academic research on Christian nationalism has revealed a considerable amount about the scope of its relationships to public policy views in the US. However, work thus far has not addressed an essential question: why now? Research by the authors of this Element advances answers, showcasing how deeper engagement with 'the 3Ms' – measurement, mechanisms and mobilization – can help unpack how and why Christian nationalism has entered our politics as a partisan project. Indeed, it is difficult to understand the dynamics of Christian nationalism without reference to the parties, as it has been a worldview used to mobilize Republicans while simultaneously recruiting and demobilizing Democrats. The mechanisms of these efforts hinge on a deep desire for social dominance that is ordained by God – an order elites suggest is threatened by Democrats and 'the left.' These elite appeals can have sweeping consequences for opinion and action, including the public's support for democratic processes.
The Geometry of Cubic Hypersurfaces
Authors: Huybrechts Daniel
Published: June 2023

Cubic hypersurfaces are described by almost the simplest possible polynomial equations, yet their behaviour is rich enough to demonstrate many of the central challenges in algebraic geometry. With exercises and detailed references to the wider literature, this thorough text introduces cubic hypersurfaces and all the techniques needed to study them. The book starts by laying the foundations for the study of cubic hypersurfaces and of many other algebraic varieties, covering cohomology and Hodge theory of hypersurfaces, moduli spaces of those and Fano varieties of linear subspaces contained in hypersurfaces. The next three chapters examine the general machinery applied to cubic hypersurfaces of dimension two, three, and four. Finally, the author looks at cubic hypersurfaces from a categorical point of view and describes motivic features. Based on the author's lecture courses, this is an ideal text for graduate students as well as an invaluable reference for researchers in algebraic geometry.
Systemic Functional Grammar
Authors: Martin J.R. , Quiroz Beatriz , Wang Pin
Published: June 2023

Systemic Functional Linguistics (SFL) is a usage-based theory of language, founded on the assumption that language is shaped entirely by its various functions in the contexts in which it used. The first of its kind, this book advances SFL by applying it comparatively to English, Spanish and Chinese. By analysing English alongside two other, typologically very different major world languages, it shows how SFL can effectively address two central issues in linguistics – namely typology and universals. It concentrates in particular on argumentation, carefully explaining how descriptions of nominal group, verbal group and clause systems and structures are motivated, and draws on examples from key texts which display a full range of ideational, interpersonal and textual grammar resources. By working across three world languages from a text-based perspective, and demonstrating how grammar descriptions can be developed and improved, the book establishes the foundations for a groundbreaking functional approach to language typology.
The Vanished Settlers of Greenland
Authors: Rix Robert
Published: June 2023

For four hundred years, Norse settlers battled to make southern Greenland a new, sustainable home. They strove against gales and winter cold, food shortages and in the end a shifting climate. The remnants they left behind speak of their determination to wrest an existence at the foot of this vast, icy and challenging wilderness. Yet finally, seemingly suddenly, they vanished; and their mysterious disappearance in the fifteenth century has posed a riddle to scholars ever since. What happened to the lost Viking colonists? For centuries people assumed their descendants could still be living, so expeditions went to find them: to no avail. Robert Rix tells the gripping story of the missing pioneers, placing their poignant history in the context of cultural discourse and imperial politics. Ranging across fiction, poetry, navigation, reception and tales of exploration, he expertly delves into one of the most contested questions in the annals of colonization.
Not Just in Time
Authors: Ain Mark , Floyd Jim
Published: June 2023

How a tiny start-up slayed an industry giant before redefining the way workers are managed around the globe.
The axisymmetric screech tones of round twin jets examined via linear stability theory
Authors: Stavropoulos Michael N. , Mancinelli Matteo , Jordan Peter , Jaunet Vincent , Weightman Joel , Edgington-Mitchell Daniel M. , Nogueira Petrônio A.S.
Published: June 2023

Spatial linear stability analysis is used to study the axisymmetric screech tones generated by twin converging round nozzles at low supersonic Mach numbers. Vortex-sheet and finite-thickness models allow for identification of the different waves supported by the flow at different conditions. Regions of the frequency–wavenumber domain for which the upstream-propagating guided jet modes are observed to be neutrally stable are observed to vary as a function of solution symmetry, jet separation,$S$, and the velocity profile used. Screech-frequency predictions performed using wavenumbers obtained from both models agree well with experimental data. Predictions obtained from the finite-thickness model better align with the screech tones measured experimentally and so are seen to be an improvement on predictions made with the vortex sheet. Additionally, results from the finite-thickness model predict both symmetric and antisymmetric screech tones for low$S$that are found in the vortex-sheet model only at greater$S$. The present results indicate that the feedback loop generating these screech tones is similar to that observed for single-jet resonance, with equivalent upstream and downstream modes.
Swallow-tailed separation bubble on a low-aspect-ratio trapezoidal plate: effects of near-wall spanwise flow
Authors: Zhu Yichen , Wang Jinjun , Xu Yang , Qu Yuan , Long Yanguang
Published: June 2023

The three-dimensional flow over a low-aspect-ratio (low-

$A\!R$

) trapezoidal plate is investigated experimentally with a focus on how the tip effects impact the structure and dynamics of the separation bubble. The chord-based Reynolds number is

$5800$

, and the angle of attack varies from

$4^\circ$

to

$10^\circ$

. Once the flow separates, the separation bubble emerges and features a swallow-tailed structure that shrinks near the midspan, which is first found for the flows over low-

$A\!R$

plates. This structure develops into the conventional single-tailed structure as the angle of attack increases. Moreover, the vortex shedding within the swallow-tailed separation bubble is restored from multiple asynchronously measured local velocity fields. It is revealed that the leading-edge vortex undergoes the novel transformation from a C-shape vortex into an M-shape vortex. This vortex transformation stems from the mass transport of the near-wall spanwise flow, which affects the fluid motion on the windward side of the C-shape vortex head, strengthening and accelerating the vortex head. The strengthened vortex head facilitates the entrainment of high-momentum fluid from the outer flow. This is responsible for the formation of the swallow-tailed structure. These findings help to fill the gaps left by the downwash at low angles of attack for low-

$A\!R$

wings, and are of value in improving the cruising and gliding performance of micro-air vehicles.
South American Maize and Political Economy of the Middle and Late Formative Soconusco Region of Guatemala
Authors: Hart Thomas C. , Duncan Neil A. , Pearsall Deborah M. , Love Michael W.
Published: June 2023

We present macrobotanical, starch, and phytolith data from artifacts and sediments from Middle Formative La Blanca (1000–600 cal BC) and Late Formative El Ujuxte (600 cal BC–cal AD 115 ) in the Soconusco region in Guatemala. Potential economic plants identified included palm (cf. Arecaceae), two varieties of maize (Zea mays), guava (Psidium guajava), bean (Phaseolus), chili peppers (Capsicum), squash (Cucurbitaceae), custard apple (Annonaceae), coco plum (Chrysobalanaceae), lerén (Calathea), arrowroot (Maranta), and bird-of-paradise (Heliconia). The results suggest that control of food production and consumption was critical for the transition from complex chiefdoms during the Middle Formative to the archaic state in the Late Formative. The arrival of a more productive South American variety of maize at El Ujuxte (about 2549 BP) allowed elites to exploit an already existing broad-based economic system and to use the maize-based religious system to increase control over maize agricultural practices and maintain power through ideology and disciplinary power. These data suggest that the arrival of fully domesticated South American maize likely influenced the overall development of Mesoamerican state-level societies.
Ayurgenomics-based frameworks in precision and integrative medicine: Translational opportunities
Authors: Mukerji Mitali
Published: June 2023

In today’s globalized and flat world, a patient can access and seek multiple health and disease management options. A digitally enabled participatory framework that allows an evidence-based informed choice is likely to assume an immense importance in the future. In India, traditional knowledge systems, like Ayurveda, coexist with modern medicine. However, due to limited crosstalk between the clinicians of both disciplines, a patient attempts integrative medicine by seeking both options independently with limited understanding and evidence. There is a need for an integrative medicine platform with a formalized approach, which allows practitioners from the two diverse systems to crosstalk, coexist, and coevolve for an informed cross-referral that benefits the patients. To be successful, this needs frameworks that enable the bridging of disciplines through a common interface with shared ontologies. Ayurgenomics is an emerging discipline that explores the principles and practices of Ayurveda combined with genomics approaches for mainstream integration. The present review highlights how in conjunction with different disciplines and technologies this has provided frameworks for (1) the discovery of molecular correlates to build ontological links between the two systems, (2) the discovery of biomarkers and targets for early actionable interventions, (3) understanding molecular mechanisms of drug action from its usage perspective in Ayurveda with applications in repurposing, (4) understanding the network and P4 medicine perspective of Ayurveda through a common organizing principle, (5) non-invasive stratification of healthy and diseased individuals using a compendium of system-level phenotypes, and (6) developing evidence-based solutions for practice in integrative medicine settings. The concordance between the two contrasting streams has been built through extensive explorations and iterations of the concepts of Ayurveda and genomic observations using state-of-the-art technologies, computational approaches, and model system studies. These highlight the enormous potential of a trans-disciplinary approach in evolving solutions for personalized interventions in integrative medicine settings.
Civic Responses to Police Violence
Authors: ANG DESMOND , TEBES JONATHAN
Published: June 2023

Roughly a thousand people are killed by American law enforcement officers each year, accounting for more than 5% of all homicides. We estimate the causal impact of these events on civic engagement. Exploiting hyperlocal variation in how close residents live to a killing, we find that exposure to police violence leads to significant increases in registrations and votes. These effects are driven entirely by Black and Hispanic citizens and are largest for killings of unarmed individuals. We find corresponding increases in support for criminal justice reforms, suggesting that police violence may cause voters to politically mobilize against perceived injustice.
Characteristics of food establishments registered with a meal delivery app in Latin America
Authors: de Paula Matos Juliana , Julião Karen Carolina Martins , Horta Paula Martins
Published: June 2023

Numerous studies have characterised the establishments registered with meal delivery apps (MDA) in several countries. However, little evidence is available regarding these platforms in Latin America (LA). The purpose of this study is to characterise food establishments registered with an MDA in nine LA cities. The establishments (n 3339) were characterised by the following keyword groups: ‘Typical cuisine’, ‘Meat and fish’, ‘Snacks’, ‘Breakfast’, ‘Desserts’ and ‘Healthy’. In addition, we identified the marketing strategies present in the establishments’ advertisements: photos, discounts and free delivery. Mexico City had the highest number of establishments registered with MDA (773), followed by Bogotá (655), Buenos Aires (567) and São Paulo (454). There is a direct relationship between the number of inhabitants of the cities and the number of the registered establishments. ‘Snacks’ was the keyword group most used by establishments in five of the nine cities. Establishments in two cities were most often characterised by the terms ‘Typical cuisine’ (Mexico City and Santiago de Chile) and ‘Meats and fish’ (Quito and San Jose). Photos were present in the advertisements of at least 84·0 % of the establishments. In addition, at least 40 % of establishments in Montevideo, Bogotá, São Paulo, Lima and Santiago de Chile offered discounts. Free delivery was present in at least 50 % of establishments in Quito, San Jose, Mexico City, Santiago de Chile and Lima. Photos were also the most common marketing strategy used by the establishments classified in all groups of keywords, while free delivery and discounts differed among them.
TRANSPOSITION AT VIRGIL, AENEID 8.612–13
Authors: Nathan Jonathan
Published: June 2023

This article argues that two words in line 8.612 of the Aeneid, promissa and perfecta, have been transposed since the poem's composition, and that the restoration of their correct order yields a preferable sense. This corruption would have happened at an early stage in the poem's transmission, but there is some reason to believe that Servius’ comment on the verse reflects its original state.
How Does Khashabi Theatre Produce a ‘Dual Presence’ of Palestinian Urbanism? Ghosts and Memory in Its First Season, Haifa, 2015–2016
Authors: YERUSHALMI DORIT
Published: June 2023

This article casts a spotlight on Khashabi Theatre, one of several independent Palestinian venues in Haifa. It explores Khashabi's dramaturgical–performative discourse with ghosts, and thereby examines how it produces a ‘dual presence’ of Palestinian urbanism: the ghostly presence of victims of history who were uprooted from the city, and the presence of the contemporary community that, by converging at the theatre, plays a key part in the revival of urban leisure culture. The article discusses the particular location of the theatre in the city and the dramaturgical characteristics of the two plays staged in the first season. It also examines the objects and the actors’ bodies as elements that evoke and conjure up ghosts, and shows how artistic practice, which allows alternative places to be established, plays a key role in the struggle for the ‘right to the city’, which is also the struggle for the ‘right of return’.
‘Stalin Died but Not Completely’: On the Theatrical Legacy of Totalitarian Catastrophe
Authors: MEERZON YANA
Published: June 2023

I began working on this article in the winter of 2022, when Russia's invasion of Ukraine shattered the fragile stability of Europe. Artur Solomonov's tragifarce How We Buried Josef Stalin (2019) speaks directly to this catastrophic time but also to the legacy of Stalinism in Russia. ‘A play about flexibility and immortality’, Solomonov's farce confronts its audience with the dilemma of Stalinism, which Putin's putrid regime continues to mobilize. Using irony, hyperbole and grotesque, it proposes a dramaturgical response to the question of why hostility to the world, isolationism and nationalistic aspirations are deeply ingrained in the collective psyche of Russian society. To Solomonov, the issue rests in the malleability of a Russian psyche that embraces an image of the tyrant and allows it to remain immortal; it also feeds Russian collective nostalgia, which prepared the ground for the rise of what Lev Gudkov called ‘recurring totalitarianism’.
How the Teatro Olimpico and the Drottingholm Slottsteater ‘Perform’ Their Pasts
Authors: MENTA ED
Published: June 2023

Is it possible for audiences to be transported to the theatrical past? Though the landmark theatres Teatro Olimpico and Drottningholm Slottsteater appear to differ completely, the meanings of their pasts are interpreted through the concepts of historicity versus historicism. After briefly examining the theatres’ histories and the historiography of their place in theatre history, we then analyse the details of the Olimpico's and Slottsteater's ‘performances’ in the following characteristics: how their distinctive features employ motion and space, the presence of their silent ghost audiences, their similarities as one-room theatres and in the ‘democratic nature’ of their auditoriums, and their use of trompe l'oeil in their construction. Through these elements, the Teatro Olimpico and Drottningholm Slottsteater perform their pasts, achieving their status as iconic playhouses that still make an impact on audiences and visitors. Does that impact effectively ‘take us back in time’?
Building a pedagogic spellchecker for L2 learners of Spanish
Authors: Blázquez-Carretero Miguel
Published: June 2023

In 2016, Lawley proposed an easy-to-build spellchecker specifically designed to help second language (L2) learners in their writing process by facilitating self-correction. The aim was to overcome the disadvantages to L2 learners posed by generic spellcheckers (GSC), such as that embedded in Microsoft Word. Drawbacks include autocorrection, misdiagnoses, and overlooked errors. With the aim of imparting explicit L2 spelling knowledge, this correcting tool does not merely suggest possible alternatives to the detected error but also provides explanations of any relevant spelling patterns. Following Lawley’s (2016) recommendations, the present study developed a prototype computer-based pedagogic spellchecker (PSC) to aid L2 learners in self-correcting their written production in Spanish. First, a corpus was used to identify frequent spelling errors of Spanish as a foreign language (SFL) learners. Handcrafted feedback was then designed to tackle the commonest misspellings. To subsequently evaluate this PSC’s efficacy in error detection and correction, another learner Spanish corpus was used. Sixty compositions were analysed to determine the PSC’s capacity for error recognition and feedback provision in comparison with that of a GSC. Results indicate that the PSC detected over 90% of the misspellings, significantly outperforming the GSC in error detection. Both provided adequate feedback on two out of three detected errors, but the pedagogic nature of the former has the added advantage of facilitating self-learning (Blázquez-Carretero & Woore, 2021). These findings suggest that it is feasible to develop spellcheckers that provide synchronous feedback, allowing SFL learners to confidently self-correct their writing while saving time and effort on the teacher’s part.
Risk factors characterisation for CHD: a case–control study in Bogota and Cali, Colombia, 2002–2020
Authors: Portilla R. Esteban , Harizanov Vyara , Sarmiento Karen , Holguín Jorge , Gracia Gloria , Hurtado-Villa Paula , Zarante Ignacio
Published: June 2023

Objective:

CHDs correspond to 28% of all congenital anomalies, being the leading cause of infant mortality in the first year of life. Thus, it is essential to explore risk factors for CHDs presentation, allowing the detection of probable cases within a population.

Methods:

We identified newborns with CHDs within a cohort from the Program for the Prevention and Monitoring of Congenital Defects in Bogota and Cali, 2002–2020. Cases were classified as isolated, complex isolated, polymalformed, and syndromic. Variables were analysed by comparing case and control averages with Student’s t test using a 95% confidence level.

Results:

Prevalence obtained was 19.36 per 10 000 live births; non-specified CHD, ventricular septal defect, and atrial septal defect were the most prevalent. As risk factors were found: paternal and maternal age above 45 years, pregestational diabetes, mother’s body mass index above 25, low educational level, and socio-economic status. As protective factors: folic acid consumption within the first trimester and pregestational period.

Conclusion:

Different risk and protective factors associated with the presentation of CHDs have been described. We consider that public health strategies should be aimed to reduce risk factors exposure. Also, improving diagnosis and prognosis by having a close monitoring on high-risk patients.
Impact of genetic variants within serotonin turnover enzymes on human cerebral monoamine oxidase A in vivo
Authors: Spies Marie , Murgaš Matej , Vraka Chrysoula , Philippe Cecile , Gryglewski Gregor , Nics Lukas , Balber Theresa , Baldinger-Melich Pia , Hartmann Annette M. , Rujescu Dan , Hacker Marcus , Winkler-Pjrek Edda , Winkler Dietmar , Lanzenberger Rupert
Published: June 2023

Variants within the monoamine oxidase A (MAO-A, MAOA) and tryptophan hydroxylase 2 (TPH2) genes, the main enzymes in cerebral serotonin (5-HT) turnover, affect risk for depression. Depressed cohorts show increased cerebral MAO-A in positron emission tomography (PET) studies. TPH2 polymorphisms might also influence brain MAO-A because availability of substrates (i.e. monoamine concentrations) were shown to affect MAO-A levels. We assessed the effect of MAOA (rs1137070, rs2064070, rs6323) and TPH2 (rs1386494, rs4570625) variants associated with risk for depression and related clinical phenomena on global MAO-A distribution volume (VT) using [11C]harmine PET in 51 participants (21 individuals with seasonal affective disorder (SAD) and 30 healthy individuals (HI)). Statistical analyses comprised general linear models with global MAO-A VT as dependent variable, genotype as independent variable and age, sex, group (individuals with SAD, HI) and season as covariates. rs1386494 genotype significantly affected global MAO-A VT after correction for age, group and sex (p < 0.05, corr.), with CC homozygotes showing 26% higher MAO-A levels. The role of rs1386494 on TPH2 function or expression is poorly understood. Our results suggest rs1386494 might have an effect on either, assuming that TPH2 and MAO-A levels are linked by their common product/substrate, 5-HT. Alternatively, rs1386494 might influence MAO-A levels via another mechanism, such as co-inheritance of other genetic variants. Our results provide insight into how genetic variants within serotonin turnover translate to the cerebral serotonin system. Clinicaltrials.gov Identifier: NCT02582398. EUDAMED Number: CIV-AT-13-01-009583.
Adaptive bias correction for improved subseasonal forecasting
Authors: Mouatadid Soukayna , Orenstein Paulo , Flaspohler Genevieve , Cohen Judah , Oprescu Miruna , Fraenkel Ernest , Mackey Lester
Published: June 2023

Subseasonal forecasting—predicting temperature and precipitation 2 to 6 weeks ahead—is critical for effective water allocation, wildfire management, and drought and flood mitigation. Recent international research efforts have advanced the subseasonal capabilities of operational dynamical models, yet temperature and precipitation prediction skills remain poor, partly due to stubborn errors in representing atmospheric dynamics and physics inside dynamical models. Here, to counter these errors, we introduce anadaptive bias correction(ABC) method that combines state-of-the-art dynamical forecasts with observations using machine learning. We show that, when applied to the leading subseasonal model from the European Centre for Medium-Range Weather Forecasts (ECMWF), ABC improves temperature forecasting skill by 60–90% (over baseline skills of 0.18–0.25) and precipitation forecasting skill by 40–69% (over baseline skills of 0.11–0.15) in the contiguous U.S. We couple these performance improvements with a practical workflow to explain ABC skill gains and identify higher-skill windows of opportunity based on specific climate conditions.
Mechanistic studies of a lipase unveil effect of pH on hydrolysis products of small PET modules
Authors: Świderek Katarzyna , Velasco-Lozano Susana , Galmés Miquel À. , Olazabal Ion , Sardon Haritz , López-Gallego Fernando , Moliner Vicent
Published: June 2023

Biocatalysis is a key technology enabling plastic recycling. However, despite advances done in the development of plastic-degrading enzymes, the molecular mechanisms that govern their catalytic performance are poorly understood, hampering the engineering of more efficient enzyme-based technologies. In this work, we study the hydrolysis of PET-derived diesters and PET trimers catalyzed by the highly promiscuous lipase B from Candida antarctica (CALB) through QM/MM molecular dynamics simulations supported by experimental Michaelis–Menten kinetics. The computational studies reveal the role of the pH on the CALB regioselectivity toward the hydrolysis of bis-(hydroxyethyl) terephthalate (BHET). We exploit this insight to perform a pH-controlled biotransformation that selectively hydrolyzes BHET to either its corresponding diacid or monoesters using both soluble and immobilized CALB. The discoveries presented here can be exploited for the valorization of BHET resulting from the organocatalytic depolymerization of PET.
Gold-catalyzed four-component multifunctionalization of alkynes
Authors: Fang Shangwen , Han Jie , Zhu Chengjian , Li Weipeng , Xie Jin
Published: June 2023

The alkyne unit is a versatile building block in organic synthesis and the development of selective multifunctionalization of alkynes is an important object of research in this field. Herein, we report an interesting gold-catalyzed, four-component reaction that achieves the oxo-arylfluorination or oxo-arylalkenylation of internal aromatic or aliphatic alkynes, efficiently breaking a carbon-carbon triple bond and forming four new chemical bonds. The reaction divergence can be controlled by site-directing functional groups in the alkynes; the presence of a phosphonate unit favors the oxo-arylfluorination, while the carboxylate motif benefits oxo-arylalkenylation. This reaction is enabled by an Au(I)/Au(III) redox coupling process using Selectfluor as both an oxidant and a fluorinating reagent. A wide range of structurally diverse α,α-disubstituted ketones, and tri- or tetra-substituted unsaturated ketones have been prepared in synthetically valuable yields and with excellent chemo-, regio- and stereoselectivity. The gram-scale preparation and late-stage application of complex alkynes have further enhanced their synthetic value.
N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics
Authors: Koo Tin-Yan , Lai Hinyuk , Nomura Daniel K. , Chung Clive Yik-Sham
Published: June 2023

Cysteine has been exploited as the binding site of covalent drugs. Its high sensitivity to oxidation is also important for regulating cellular processes. To identify new ligandable cysteines which can be hotspots for therapy and to better study cysteine oxidations, we develop cysteine-reactive probes,N-acryloylindole-alkynes (NAIAs), which have superior cysteine reactivity owing to delocalization of π electrons of the acrylamide warhead over the whole indole scaffold. This allows NAIAs to probe functional cysteines more effectively than conventional iodoacetamide-alkyne, and to image oxidized thiols by confocal fluorescence microscopy. In mass spectrometry experiments, NAIAs successfully capture new oxidized cysteines, as well as a new pool of ligandable cysteines and proteins. Competitive activity-based protein profiling experiments further demonstrate the ability of NAIA to discover lead compounds targeting these cysteines and proteins. We show the development of NAIAs with activated acrylamide for advancing proteome-wide profiling and imaging ligandable cysteines and oxidized thiols.
Reaction performance prediction with an extrapolative and interpretable graph model based on chemical knowledge
Authors: Li Shu-Wen , Xu Li-Cheng , Zhang Cheng , Zhang Shuo-Qing , Hong Xin
Published: June 2023

Accurate prediction of reactivity and selectivity provides the desired guideline for synthetic development. Due to the high-dimensional relationship between molecular structure and synthetic function, it is challenging to achieve the predictive modelling of synthetic transformation with the required extrapolative ability and chemical interpretability. To meet the gap between the rich domain knowledge of chemistry and the advanced molecular graph model, herein we report a knowledge-based graph model that embeds the digitalized steric and electronic information. In addition, a molecular interaction module is developed to enable the learning of the synergistic influence of reaction components. In this study, we demonstrate that this knowledge-based graph model achieves excellent predictions of reaction yield and stereoselectivity, whose extrapolative ability is corroborated by additional scaffold-based data splittings and experimental verifications with new catalysts. Because of the embedding of local environment, the model allows the atomic level of interpretation of the steric and electronic influence on the overall synthetic performance, which serves as a useful guide for the molecular engineering towards the target synthetic function. This model offers an extrapolative and interpretable approach for reaction performance prediction, pointing out the importance of chemical knowledge-constrained reaction modelling for synthetic purpose.
Structural insight into the human SID1 transmembrane family member 2 reveals its lipid hydrolytic activity
Authors: Qian Dandan , Cong Ye , Wang Runhao , Chen Quan , Yan Chuangye , Gong Deshun
Published: June 2023

The systemic RNAi-defective (SID) transmembrane family member 2 (SIDT2) is a putative nucleic acid channel or transporter that plays essential roles in nucleic acid transport and lipid metabolism. Here, we report the cryo-electron microscopy (EM) structures of human SIDT2, which forms a tightly packed dimer with extensive interactions mediated by two previously uncharacterized extracellular/luminal β-strand-rich domains and the unique transmembrane domain (TMD). The TMD of each SIDT2 protomer contains eleven transmembrane helices (TMs), and no discernible nucleic acid conduction pathway has been identified within the TMD, suggesting that it may act as a transporter. Intriguingly, TM3-6 and TM9-11 form a large cavity with a putative catalytic zinc atom coordinated by three conserved histidine residues and one aspartate residue lying approximately 6 Å from the extracellular/luminal surface of the membrane. Notably, SIDT2 can hydrolyze C18 ceramide into sphingosine and fatty acid with a slow rate. The information presented advances the understanding of the structure-function relationships in the SID1 family proteins.
Dopamine and vesicular monoamine transport loss supports incidental Lewy body disease as preclinical idiopathic Parkinson
Authors: Pifl Christian , Reither Harald , Attems Johannes , Zecca Luigi
Published: June 2023

Incidental Lewy body disease (ILBD) is a neuropathological diagnosis of brains with Lewy bodies without clinical neuropsychiatric symptoms. Dopaminergic deficits suggest a relationship to preclinical Parkinson’s disease (PD). We now report a subregional pattern of striatal dopamine loss in ILBD cases, with dopamine found significantly decreased in the putamen (−52%) and only to a lower extent in the caudate (−38%, not statistically significant); this is similar to the pattern in idiopathic PD in various neurochemical and in vivo imaging studies. We aimed to find out if our recently reported impaired storage of dopamine in striatal synaptic vesicles prepared from striatal tissue of cases with idiopathic PD might be an early or even causative event. We undertook parallel measurements of [3H]dopamine uptake and vesicular monoamine transporter (VMAT)2 binding sites by the specific label [3H]dihydrotetrabenazine on vesicular preparation from caudate and putamen in ILBD. Neither specific uptake of dopamine and binding of [3H]dihydrotetrabenazine, nor mean values of the calculated ratios of dopamine uptake and VMAT2 binding, a measure of uptake rate per transport site, were significantly different between ILBD and controls. ATP-dependence of [3H]dopamine uptake revealed significantly higher rates in putamen than in caudate at saturating concentrations of ATP in controls, a subregional difference lost in ILBD. Our findings support a loss of the normally higher VMAT2 activity in putamen as a contributing factor to the higher susceptibility of the putamen to dopamine depletion in idiopathic PD. Moreover, we suggest ILBD postmortem tissue as a valuable source for testing hypotheses on processes in idiopathic PD.
A locally activatable sensor for robust quantification of organellar glutathione
Authors: Emmert Sarah , Quargnali Gianluca , Thallmair Sebastian , Rivera-Fuentes Pablo
Published: June 2023

Glutathione (GSH) is the main determinant of intracellular redox potential and participates in multiple cellular signalling pathways. Achieving a detailed understanding of intracellular GSH homeostasis depends on the development of tools to map GSH compartmentalization and intra-organelle fluctuations. Here we present a GSH-sensing platform for live-cell imaging, termed targetable ratiometric quantitative GSH (TRaQ-G). This chemogenetic sensor possesses a unique reactivity turn-on mechanism, ensuring that the small molecule is only sensitive to GSH in a desired location. Furthermore, TRaQ-G can be fused to a fluorescent protein to give a ratiometric response. Using TRaQ-G fused to a redox-insensitive fluorescent protein, we demonstrate that the nuclear and cytosolic GSH pools are independently regulated during cell proliferation. This sensor was used in combination with a redox-sensitive fluorescent protein to quantify redox potential and GSH concentration simultaneously in the endoplasmic reticulum. Finally, by exchanging the fluorescent protein, we created a near-infrared, targetable and quantitative GSH sensor.
Mechanistic basis for potent neutralization of Sin Nombre hantavirus by a human monoclonal antibody
Authors: Stass Robert , Engdahl Taylor B. , Chapman Nathaniel S. , Wolters Rachael M. , Handal Laura S. , Diaz Summer M. , Crowe James E. , Bowden Thomas A.
Published: June 2023

Rodent-borne hantaviruses are prevalent worldwide and upon spillover to human populations, cause severe disease for which no specific treatment is available. A potent antibody response is key for recovery from hantavirus infection. Here we study a highly neutralizing human monoclonal antibody, termed SNV-42, which was derived from a memory B cell isolated from an individual with previous Sin Nombre virus (SNV) infection. Crystallographic analysis demonstrates that SNV-42 targets the Gn subcomponent of the tetrameric (Gn−Gc)4 glycoprotein assembly that is relevant for viral entry. Integration of our 1.8 Å structure with the (Gn−Gc)4 ultrastructure arrangement indicates that SNV-42 targets the membrane-distal region of the virus envelope. Comparison of the SNV-42 paratope encoding variable genes with inferred germline gene segments reveals high sequence conservation, suggesting that germline-encoded antibodies inhibit SNV. Furthermore, mechanistic assays reveal that SNV-42 interferes with both receptor recognition and fusion during host-cell entry. This work provides a molecular-level blueprint for understanding the human neutralizing antibody response to hantavirus infection.