bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpreting as Translanguaging
Authors: Han Lili , Wen Zhisheng (Edward) , Runcieman Alan James
Published: October 2023

Drawing on the emerging literature in translanguaging theory and research, the Element provides a comprehensive analysis of the embedded model of translanguaging-in-interpreting and interpreting-in-translanguaging from theoretical and practical perspectives, buttressed by evidence from an exploratory empirical investigation. To achieve this goal, the authors first trace the emergence and historical development of the key concepts and basic tenets of translanguaging and interpreting separately and then combined. This is followed by reviews of relevant literature, synthesizing how translanguaging theories and research methods can be applied in specific domains of interpreting studies, such as community and public service interpreting. An integrated account of translanguaging and interpreting is proposed and elaborated. The theoretical and methodological implications of this integrative perspective are teased out, with a view to illuminating interpreting theory, pedagogy and instruction.
The new judicial federalism: the evolving relationship between EU and Member State courts
Authors: Zglinski Jan
Published: October 2023

A wind of change is blowing through the European judicial landscape. During the past decade, the European Union (EU) judiciary has undergone its biggest institutional overhaul in generations, the rise of authoritarian populism in Central and Eastern Europe has prompted a Rule of Law crisis, several supreme and constitutional courts challenged the supremacy of EU law, while the Court of Justice re-articulated the scope of the duty to refer under Article 267 TFEU and, for the first time, found that domestic last-instance courts breaching it triggered state liability. This Article argues that these and similar developments, once looked at together, suggest that something fundamental has shifted in the EU’s judicial architecture. A new form of judicial federalism has emerged, which departs from the traditional way in which relations between EU and Member State courts used to be structured. Although this new federalism is multifaceted and is marked by both centripetal and centrifugal forces, its distinguishing feature is a stronger centralisation, which manifests itself in a considerably expanded federal judiciary, a greater emphasis on hierarchy, a more careful use of European judicial resources, as well as tighter supervision of national procedures and court structures.
The Freedom of Solar Systems
Authors: Koschel Mathis
Published: October 2023

This essay discusses how, for Hegel, freedom can be realized in nature in a rudimentary fashion in solar systems. This solves a problem in Kant's account of freedom, namely, the problem that Kant only gives anegativeargument for why freedom isnotimpossible but does not give apositiveaccount of how freedomisreal. I give a novel account of Kant's negative argument. Then, I show how, according to Hegel, solar systems can be considered as exhibiting freedom in a rudimentary fashion. Finally, I lay out how Hegel systematically develops this point about the freedom of solar systems in the ‘Mechanism’ chapter of theScience of Logic. In doing so, he uses Kant's negative argument in a ‘purified’ form to arrive at an account of an ‘intimate token-type relation’ between the planets in a solar system and the law that governs their motion. The essay as a whole provides a concrete example of how Hegel is an inheritor and radicalizer of Kant, both with respect to freedom's reality and with respect to philosophical method.
A long-wave model for film flow inside a tube with slip
Authors: Schwitzerlett M. , Ogrosky H.R. , Topaloglu I.
Published: October 2023

A long-wave asymptotic model is developed for the flow of an axisymmetric viscous film lining the interior of a tube for the case where slip occurs at the tube wall. Both the case of a falling film with a passive air core and that of a film driven up the tube by pressure-driven airflow are considered. The impact of slip on the net liquid volume flux is discussed, and linear stability analysis of the evolution equation is conducted to identify the impact of slip on the phase speed and growth rates of disturbances in each case. The presence of slip enhances the growth rates, though its impact on phase speed depends on the film thickness and the strength of the core airflow. For some parameter combinations, slip can modify the phase speed without altering the base flow. The nonlinear evolution of the free surface is then studied numerically. For falling films, increasing the slip length reduces the critical thickness required for plug formation to occur. Families of travelling wave solutions are found via continuation and are used to derive a simple formula for the dependence of this critical thickness on the slip length; this formula is shown to hold for small slip length. For air-driven films, the topology of streamlines in the film can be altered by slip at the wall; if the slip length is large enough, it can prevent regions of recirculation from forming at the wave crest.
Against Quantitative Primitivism
Authors: Perry Zee R.
Published: October 2023

The problem of quantity is the problem of identifying what about the physical world explains why it can be so well represented with mathematical entities. I introduce “quantitative primitivism,” the dominant position in the literature, which offers only a partial solution to the problem of quantity. I argue that a reductive account of quantitativeness provides a full solution to the problem and describe two reductive accounts in the literature. I discuss some of the unique metaphysical consequences of reductive accounts of quantity, including a novel dissolution to the long-standing absolutist–comparativist debate.
Climatic and cave settings influence on drip water fluorescent organic matter with implications for fluorescent laminations in stalagmites
Authors: Endres Laura Sibylla , Jacquin Céline , González-Lemos Saúl , Rodríguez-Rodríguez Laura , Sliwinski Jakub , Kaushal Nikita , Kost Oliver , Stoll Heather Marie
Published: October 2023

Speleothem fluorescence can provide insights into past vegetation dynamics and stalagmite chronology. However, its origin and especially the formation of fluorescent laminations in stalagmites are poorly understood. We conducted a year-long monthly monitoring of drip water fluorescence in La Vallina Cave (northern Iberian Peninsula) and compared the results to drip water chemistry and active speleothems from the same sites. Drip waters were analyzed using fluorescence spectroscopy and parallel factor analysis (PARAFAC). The resulting five-component model indicates contributions from vegetation, microbial activity, and bedrock. Intra-site fluorescence variability is mainly influenced by changes in overlying vegetation, water reservoir time, and respiration rates. Contrary to prevailing views, we find no systematic increase in drip water fluorescence during rainy conditions across drip sites and seasonal variations in drip water fluorescence are absent at a location where present-day speleothem layers form. Our findings challenge the notion of a higher abundance of humic-like fluorescence during the rainy season as the primary cause for layer formation and suggest additional controls on drip water fluorescence, such as bedrock interaction and microbial reprocessing. We also propose that growth rate may control the dilation of the fluorescence signal in stalagmites, indicating other potential mechanisms for fluorescent layer formation.
BONE POINTS IN TIME: DATING HUNTER-GATHERER BONE POINTS IN THE TERRITORY OF LITHUANIA
Authors: Rimkus Tomas , Eriksen Berit Valentin , Meadows John , Hamann Christian
Published: October 2023

Bone points were one of the major hunting implements in northern European hunter-gatherer societies. They differ in shapes, types, and manufacturing techniques. In this paper, we investigate 22 bone points from the territory of Lithuania, by studying their morpho-technological characteristics, direct dates, and adhesive residues. The majority are isolated finds, but four points were selected from excavated archaeological sites dated between the 5th and 3rd millennia cal BC. Most of the points belong to the barbed points category, but six slotted points were also studied. Of the 22, 16 previously undated points were sampled for accelerator mass spectrometry radiocarbon (AMS 14C) dating. The results of 10 successfully dated samples are discussed together with previously published 14C dates of bone points from the same region. ATR-FTIR analysis of adhesive residues from six points suggest that birch bark tar was used to haft barbed points and lithic inserts. The results reveal the diversity of types of Early Holocene bone points in the territory of Lithuania, while the slotted and Kunda-type bone points fall into narrow timeframes.
Joint effects between cadmium exposure and dietary antioxidant quality score on osteoporosis and bone mineral density
Authors: Lang Huifang , Li Hongmei , Zhang Aixian , Li Na
Published: October 2023

To explore the relationship between dietary antioxidant quality score (DAQS) and Cd exposure both alone and in combination with osteoporosis and bone mineral density (BMD) among postmenopausal women. In total, 4920 postmenopausal women from the National Health and Nutrition Examination Survey were included in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses to assess the association between DAQS and Cd exposure with femur neck BMD, total femur BMD, osteoporosis among postmenopausal women, respectively, and the coexistence effect of DAQS and Cd exposure. Four hundred and ninety-nine had osteoporosis. DAQS (OR = 0·86, 95 % CI 0·77, 0·97) and high DAQS (OR = 0·60, 95 % CI 0·36, 0·99) were found to be associated with decreased odds of osteoporosis, while Cd exposure (OR = 1·34, 95 % CI 1·04, 1·72) and high Cd exposure (OR = 1·45, 95 % CI 1·02, 2·06) were related to increased odds of osteoporosis. A positive correlation was observed between high DAQS and both total femur BMD and femur neck BMD. Conversely, Cd exposure was found to be negatively correlated with total femur BMD and femur neck BMD. Additionally, taking low-Cd and high-quality DAQS group as reference, the joint effect of Cd exposure and DAQS showed greater increased odds of osteoporosis and decreased total femur BMD and femur neck BMD as Cd level and DAQS combinations worsened. There may be an interaction between Cd exposure and DAQS for femur neck BMD, total femur BMD, and osteoporosis in postmenopausal women.
Credit Default Swaps and Firm Cyclicality
Authors: Norden Lars , Yin Chao , Zhao Lei
Published: October 2023

We find firm cyclicality decreases by 40% after the inception of credit default swap (CDS) trading. The effect stems from CDS firms’ less aggressive asset growth in good times and is stronger for firms facing a more severe empty creditor problem. Important identification issues are addressed. The result cannot be explained with debt overhang, bank lending cyclicality, or the cyclicality of firms’ business fundamentals. It holds for the cyclicality of various corporate outcomes (inventories, cash, and employment). Importantly, CDS trading impedes unhealthy growth and enhances profitability and firm value. Our finding indicates an important positive real effect of financial innovation.
Evaluation of food purchasing in the Brazilian School Feeding Programme: feasibility of the requirements and recommendations
Authors: Azevedo Ana Beatriz Coelho de , Bandoni Daniel Henrique , Amorim Ana Laura Benevenuto de , Canella Daniela Silva
Published: October 2023

Objective:

To analyse the purchase of food for school feeding, according to the extent and purpose of industrial processing and variety, exploring the feasibility of achieving the requirements and recommendations of the Brazilian School Feeding Programme, and the variety of unprocessed or minimally processed foods according to the purchase of ultra-processed foods.

Design:

Secondary data from 2016 from the Accountability Management System of the National Fund for Educational Development, concerning the food items purchased, were used to explore the feasibility of the requirements and recommendations. The foods were grouped according to the NOVA classification system. Variety was assessed by counting different types of unprocessed or minimally processed foods.

Setting:

Brazil.

Participants:

3698 Brazilian municipalities.

Results:

Energy share from unprocessed or minimally processed foods was 44·1 % while that of ultra-processed foods was 29·9 %. The average of unprocessed or minimally processed food types purchased annually was 33·8 items. Of the municipalities, 35·8 % were within the limit established for the expenditure of funds for the purchase of processed and ultra-processed foods, while 8·7 % followed the recommendation for variety. The proportion of ultra-processed foods did not influence the variety of food items purchased.

Conclusions:

The results showed the feasibility of achieving the requirements and recommendations and underscored the importance of continued efforts to promote the inclusion of unprocessed or minimally processed foods in the school feeding programme while addressing the challenges associated with expenditure limits of processed and ultra-processed foods and enhancing variety, which is strategic to promote adequate and healthy meals.
Development and internal validation of the SMILE-FSS: a Free Sugars Screener for Australian children aged 2 and 5 years
Authors: Bell Lucinda K , Leemaqz Shalem , Devenish-Coleman Gemma , Do Loc G , Ha Diep , Scott Jane A , Golley Rebecca K
Published: October 2023

Objective:

To develop and internally validate a Free Sugars Screener (FSS) for Australian children aged 2 and 5 years.

Design:

Using data collected from a ninety-nine-item (2-year-olds) and ninety-eight-item (5-year-olds) FFQ in the Study of Mothers’ and Infants’ Life Events affecting oral health (SMILE-FFQ), a regression-based prediction modelling approach was employed to identify a subset of items that accurately estimate total free sugars intake (FSI). The predictors were grams of free sugars (FSg) for individual items in the SMILE-FFQ and child’s age and sex. The outcome variable was total FSI per person. To internally validate the SMILE-FSS items, the estimated FSg was converted to percent energy from free sugars (%EFS) for comparison to the WHO free sugars guideline categories (< 5 %, 5–< 10 % and ≥ 10 %EFS) using cross-classification analysis.

Setting:

Australia.

Participants:

858 and 652 2- and 5-year-old children, respectively, with complete dietary (< 5 % missing) and sociodemographic data.

Results:

Twenty-two and twenty-six items were important in predicting FSI at 2 and 5 years, respectively. Items were similar between ages with more discretionary beverage items (e.g. sugar-sweetened beverages) at 5 years. %EFS was overestimated by 4·4 % and 2·6 %. Most children (75 % and 82 %) were categorised into the same WHO free sugars category with most (87 % and 95 %) correctly identified as having < 10 %EFS in line with the WHO recommendation.

Conclusions:

The SMILE-FSS has good internal validity and can be used in research and practice to estimate young Australian children’s FSI and compare to the WHO free sugars guidelines to identify those ‘at risk’.
Disaster Preparedness Evaluation Tool (DPET): Adaptation and psychometric evaluation for nurses in Germany
Authors: Beckert Joachim , Zeeb Hajo , De Santis Karina Karolina
Published: October 2023

Abstract: Background: The Disaster Preparedness Evaluation Tool (DPET) with 47 items was developed to assess the disaster preparedness level among nurses in the USA. Aim: This study aimed (1) to adapt and validate the DPET for the nursing context in Germany and (2) to perform its psychometric evaluation. Methods: The DPET items were translated to German (DPET-GER). Adaptation was performed to identify irrelevant items and content validity was estimated using the scale-level content validity index (S-CVI) based on expert ratings. Psychometric evaluation was performed based on data from an online survey of 317 nurses. Internal consistency (Cronbach’s alpha) and factor structure were assessed with an exploratory factor analysis. Results: Ten items were unanimously rated as irrelevant by four experts and removed. Based on ratings by further seven experts, the content validity of DPET-GER was low for all 37 items (S-CVI of 0.53) or moderate for 19 items rated as relevant (S-CVI of 0.74). The internal consistency of DPET-GER was high (Cronbach’s alpha of 0.94) and 37 items were reduced to five factors that explain 55% of variance in all items. Conclusions: The DPET-GER has acceptable psychometric properties (internal consistency and factor structure). However, low content validity indicates that further adaptation of the DPET-GER is required before it could be used to assess disaster preparedness among nurses in Germany. More research is also needed to contextualize the construct of disaster preparedness.
Measures to protect and promote elite athletes’ mental health in Swiss sports
Authors: Röthlin Philipp , Horvath Stephan , Birrer Daniel
Published: October 2023

Abstract: Introduction: This paper addresses the growing concern surrounding mental health in elite sports. Acknowledging that national sports systems vary in structure and that any evaluation of these issues must necessarily be country-specific, the study explores current mental health provisions in Switzerland. Method: Based on the feedback of 31 experts, including athletes and representatives from sporting organizations, the study evaluates four aspects of existing measures: formulation of a mental health plan, mental health care provision, athlete support systems, and provisions for high-risk events. Results: The findings highlight two key issues. First, experts clearly have different views about mental health initiatives in Swiss sports for reasons that may include variations in access to information, program visibility, regional and sport-specific differences, and emerging strategies that have not yet been widely embraced. Second, despite these disparities, the experts unanimously agreed that some basic mental health measures remain unimplemented. Conclusion: These findings highlight a pressing need for basic interventions such as mental health screening and improved mental health literacy. Another recommended priority is to design and implement a holistic national mental health plan informed by the collaborative contributions of all stakeholders. Furthermore, this discourse on mental health must be in coordination with ongoing dialogues on ethics in sports.
Prevalence of Deformation‐Scale Surface Currents
Authors: Palóczy A. , LaCasce J. H.
Published: October 2023

Understanding the transport of large ocean currents, like the Gulf Stream, has been of interest since the early days of oceanography. There has been less attention on the widths of the currents, although there exist several theoretical predictions. We present a census of time‐averaged jet profiles, using in situ and satellite data. The jets are typically asymmetrical, being narrower on the side with weaker stratification. The half‐widths Lj are correlated with the local deformation radius Ld associated with the first surface mode on either side. The dependence of Lj on Ld is predicted by simple shallow water geostrophic adjustment models, with or without outcropping layers. This implies that potential vorticity is well‐mixed adjacent to the jets, due most likely to mesoscale eddies. The findings suggest that surface jet widths are determined locally, by eddy‐mean flow interactions.
Effects of Mixing at Pore Intersections on Large‐Scale Dissolution Patterns and Solute Transport
Authors: Sharma Rishabh P. , Deng Jingxuan , Kang Peter K. , Szymczak Piotr
Published: October 2023

The flow‐induced dissolution of porous rocks governs many important subsurface processes and applications. Solute mixing, which determines pore‐scale concentration fields, is a key process that affects dissolution. Despite its importance, the effects of pore‐scale mixing on large‐scale dissolution patterns have not been investigated. Here, we use a pore network model to elucidate the mixing effects on macroscopic dissolution patterns and solute transport. We consider two mixing rules at pore intersections that represent two end members in terms of the mixing intensity. We observe that the mixing effect on dissolution is the strongest at moderate Damköhler number, when the reactive and advective time scales are comparable. This is the regime where wormholes spontaneously appear. Incomplete mixing is shown to enhance flow focusing at the tips of the dissolution channels, which results in thinner wormholes and shorter breakthrough times. These effects on passive solute transport are evident independent of initial network heterogeneity.
Diverse Ionospheric Disturbances by the 2022 Hunga Tonga‐Hunga Ha'apai Eruption Observed by a Dense GNSS Array in New Zealand
Authors: Muafiry Ihsan Naufal , Wijaya Dudy D. , Meilano Irwan , Heki Kosuke
Published: October 2023

Using a network of global navigation satellite systems receivers in New Zealand, located 2,000–3,300 km southwest of Hunga Tonga‐Hunga Ha'apai volcano, we found at least three different kinds of ionospheric disturbances from changes in total electron contents (TEC). Ionospheric signatures of the near‐field acoustic wave propagating ∼0.8 km/s were not clear in New Zealand due possibly to large geometric decay. The first disturbance emerged ∼1 hr after the eruption and traveled toward southwest with a speed of ∼0.6 km/s. This, together with the subsequent disturbance propagating by ∼0.4 km/s, suggests its link to the ahead‐of‐tsunami ionospheric disturbance, excited by the Lamb wave and subsequent tsunamis traveling in the Pacific Ocean. The second disturbance started ∼2 hr after the eruption as tens of waves with periods 10–15 min propagating by ∼0.3 km/s, possibly internal gravity waves (IGW) excited by the passages of the Lamb wave. Such IGW wave trains continued until ∼10 hr after the eruption. The Lamb wave traveled round the earth, and its second and third passages disturbed the ionosphere in New Zealand on the next day as similar IGW wave trains following the Lamb wave. The third disturbance occurred as an enhancement of the harmonic oscillation of TEC with frequency of ∼3.7 mHz, ∼14 hr after the eruption. This might be an atmospheric mode excited by the eruption, but its propagation and sudden activation remain unexplained.
Urbanization Impacts on Tropical Cyclone Rainfall Extremes‐Inferences From Observations and Convection‐Permitting Model Experiments Over South China
Authors: Hu Chenxi , Tam Chi‐Yung , Loi Chi Lok , Cheung Kevin K. W. , Li Yubin , Yang Zong‐Liang , Au‐Yeung Yee Man , Fang Xiaoyi , Niyogi Dev
Published: October 2023

How urbanization affects tropical cyclone (TC) rainfall is inferred from station observations over the Great Bay Area (GBA, located on the South China coast) and numerical model experiments. Observations from 41 TCs indicate that surface wind is noticeably weaker in urban compared to rural stations during TC passages, while the urban heat island effect is considerably suppressed. Extreme (99th percentile of) hourly rainfall for these TC events during 2008–2017 is more intense over urban compared to rural stations. For eight selected TC cases, dynamical downscaling was carried out using the convection‐resolving Weather Research and Forecasting model, each with three parallel experiments: “Nourban” in which the urban area was replaced by cropland; “AH0” (“AH300”) in which the diurnal maximum anthropogenic heat (AH) was set to 0 (300 W/m2) in city locations. Both AH0 and AH300 show a significant increase in urban hourly rainfall intensity and probability in all ranges (most obvious for heavy rainfall >40 mm/hr), over the GBA mega‐city. Further diagnosis indicates increased moisture flux convergence in urban areas over a 2‐day period during the landfall, contributes to increased rainfall, likely induced by the surface roughness. The influence of AH, however, is found to be insignificant. The increase in accumulated rainfall due to urbanization is proportional to the storm residence time over the city, implying greater rainfall exacerbation for slower or larger TCs. Overall, urbanization intensifies extreme TC rainfall over the coastal GBA mega‐city mainly due to surface frictional convergence, with stronger intensification for storms residing longer over the city.
Decadal Variations in the Summer Precipitation Over Eastern China Associated With Spring Arctic Sea Ice
Authors: Qian Danwei , Huang Yanyan , Li Huixin , Zhou Botao , Yin Zhicong , Wang Huijun
Published: October 2023

This study investigated the contribution of Arctic sea ice concentration (SIC) on decadal variations of the dominant mode of summer precipitation over eastern China during 1981–2020. The spatial pattern of leading empirical orthogonal function mode has changed from a dipole pattern with negative anomalies over Jianghuai Valley and positive anomalies over southern China during 1981–2001 to the Yangtze River Valley (YRV) pattern during 2002–2020. Spring SIC over Kara Sea was significantly related to the dipole pattern, through influencing Eurasian snow depth. The associated anomalous temperature gradient and atmospheric circulation affected the meridional displacement of the East Asian subtropical jet, which favored the dipole pattern of summer precipitation. For the YRV pattern, spring SIC over Greenland Sea has an impact on the sea surface temperature anomalies in the western Pacific by triggering a wave train that influenced the precipitation through the establishment of the Pacific–Japan pattern. The results of this study may provide reference value for the prediction of summer precipitation over eastern China.
Is Parental Control over Children's Eating Associated with Childhood Obesity? Results from a Population‐Based Sample of Third Graders
Authors: Robinson Thomas N. , Kiernan Michaela , Matheson Donna M. , Haydel K. Farish
Published: October 2023

Objective:Identifying parental behaviors that influence childhood obesity is critical for the development of effective prevention and treatment programs. Findings from a prior laboratory study suggest that parents who impose control over their children's eating may interfere with their children's ability to regulate intake, potentially resulting in overweight. These findings have been widely endorsed; however, the direct relationship between parental control of children's intake and their children's degree of overweight has not been shown in a generalized sample.

Research Methods and Procedures:This study surveyed 792 third‐grade children with diverse ethnic and socioeconomic backgrounds from 13 public elementary schools. Parental control over children's intake was assessed through telephone interviews using a state‐of‐the‐art instrument, and children were measured for height, weight, and triceps skinfold thickness.

Results:Counter to the hypothesis, parental control over children's intake was inversely associated with overweight in girls, as measured by body mass index,r= −0.12,p< 0.05, and triceps skinfolds,r= −0.11,p< 0.05. This weak relationship became only marginally significant when controlling for parents’ perceptions of their own weight, level of household education, and children's age. No relationship between parental control of children's intake and their children's degree of overweight was found in boys.

Discussion:Previous observations of the influence of parental control over children's intake in middle‐class white families did not generalize to 8‐ to 9‐year‐olds in families with diverse socioeconomic and ethnic backgrounds. The present findings reveal a more complex relationship between parental behaviors and children's weight status.
eQTL colocalization analysis highlights novel susceptibility genes in Autism Spectrum Disorders (ASD)
Authors: Dominguez-Alonso S. , Carracedo A. , Rodriguez-Fontenla C.
Published: October 2023

Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders (NDDs) characterized by difficulties in social interaction and communication, repetitive behavior, and restricted interests. ASD has proven to have a strong genetic component. However, defining causal genes is still one of the main challenges in GWAS, since the vast majority (>90%) of detected signals lie within the non-coding genome. Expression quantitative trait locus (eQTL) colocalization analysis determines whether a specific variant is responsible for both a local eQTL and GWAS association and has helped leverage data and rendering gene discovery for a wide array of diseases. Here we further mine the largest ASD GWAS performed to date (18,381 cases and 27,969 controls) altogether with GWAS summary statistics from the main PGC studies (Schizophrenia, MD (Major Depression) and ADHD (Attention Deficit/Hyperactivity Disorder)), by using eQTpLot, a newly developed tool that illustrates the colocalization of GWAS and eQTL signals in a locus, and the enrichment of and correlation between the candidate gene eQTLs and trait-significant variants. This analysis points up 8 genes with a significant eQTL colocalization signal in ASD (CRHR1, KANSL1, MANBA, MAPT, MMP12, NKX2-2, PTPRE and WNT3) and one gene (SRPK2) with a marginally significant colocalization signal (r = 0.69, p < 1 × 10−6), and specifically highlights the potentially causal role of MAPT (r = 0.76, p < 1 × 10−6), NKX2-2 (r = 0.71, p-value = 2.26−02) and PTPRE (r = 0.97, p-value = 2.63−04) when restricting the analysis to brain tissue.
Synthetic control of correlated disorder in UiO-66 frameworks
Authors: Tatay Sergio , Martínez-Giménez Sonia , Rubio-Gaspar Ana , Gómez-Oliveira Eloy , Castells-Gil Javier , Dong Zhuoya , Mayoral Álvaro , Almora-Barrios Neyvis , M. Padial Natalia , Martí-Gastaldo Carlos
Published: October 2023

Changing the perception of defects as imperfections in crystalline frameworks into correlated domains amenable to chemical control and targeted design might offer opportunities for the design of porous materials with superior performance or distinctive behavior in catalysis, separation, storage, or guest recognition. From a chemical standpoint, the establishment of synthetic protocols adapted to control the generation and growth of correlated disorder is crucial to consider defect engineering a practicable route towards adjusting framework function. By using UiO-66 as experimental platform, we systematically explored the framework chemical space of the corresponding defective materials. Periodic disorder arising from controlled generation and growth of missing cluster vacancies can be chemically controlled by the relative concentration of linker and modulator, which has been used to isolate a crystallographically pure “disordered” reo phase. Cs-corrected scanning transmission electron microscopy is used to proof the coexistence of correlated domains of missing linker and cluster vacancies, whose relative sizes are fixed by the linker concentration. The relative distribution of correlated disorder in the porosity and catalytic activity of the material reveals that, contrarily to the common belief, surpassing a certain defect concentration threshold can have a detrimental effect.
Cryo-EM structure of human O-GlcNAcylation enzyme pair OGT-OGA complex
Authors: Lu Ping , Liu Yusong , He Maozhou , Cao Ting , Yang Mengquan , Qi Shutao , Yu Hongtao , Gao Haishan
Published: October 2023

O-GlcNAcylation is a conserved post-translational modification that attaches N-acetyl glucosamine (GlcNAc) to myriad cellular proteins. In response to nutritional and hormonal signals, O-GlcNAcylation regulates diverse cellular processes by modulating the stability, structure, and function of target proteins. Dysregulation of O-GlcNAcylation has been implicated in the pathogenesis of cancer, diabetes, and neurodegeneration. A single pair of enzymes, the O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), catalyzes the addition and removal of O-GlcNAc on over 3,000 proteins in the human proteome. However, how OGT selects its native substrates and maintains the homeostatic control of O-GlcNAcylation of so many substrates against OGA is not fully understood. Here, we present the cryo-electron microscopy (cryo-EM) structures of human OGT and the OGT-OGA complex. Our studies reveal that OGT forms a functionally important scissor-shaped dimer. Within the OGT-OGA complex structure, a long flexible OGA segment occupies the extended substrate-binding groove of OGT and positions a serine for O-GlcNAcylation, thus preventing OGT from modifying other substrates. Conversely, OGT disrupts the functional dimerization of OGA and occludes its active site, resulting in the blocking of access by other substrates. This mutual inhibition between OGT and OGA may limit the futile O-GlcNAcylation cycles and help to maintain O-GlcNAc homeostasis.
Genome-wide association analysis of plasma lipidome identifies 495 genetic associations
Authors: Ottensmann Linda , Tabassum Rubina , Ruotsalainen Sanni E. , Gerl Mathias J. , Klose Christian , Widén Elisabeth ,   FinnGen, Simons Kai , Ripatti Samuli , Pirinen Matti
Published: October 2023

The human plasma lipidome captures risk for cardiometabolic diseases. To discover new lipid-associated variants and understand the link between lipid species and cardiometabolic disorders, we perform univariate and multivariate genome-wide analyses of 179 lipid species in 7174 Finnish individuals. We fine-map the associated loci, prioritize genes, and examine their disease links in 377,277 FinnGen participants. We identify 495 genome-trait associations in 56 genetic loci including 8 novel loci, with a considerable boost provided by the multivariate analysis. For 26 loci, fine-mapping identifies variants with a high causal probability, including 14 coding variants indicating likely causal genes. A phenome-wide analysis across 953 disease endpoints reveals disease associations for 40 lipid loci. For 11 coronary artery disease risk variants, we detect strong associations with lipid species. Our study demonstrates the power of multivariate genetic analysis in correlated lipidomics data and reveals genetic links between diseases and lipid species beyond the standard lipids.
Synthesis of tertiary alkylphosphonate oligonucleotides through light-driven radical-polar crossover reactions
Authors: Ota Kenji , Nagao Kazunori , Hata Dai , Sugiyama Haruki , Segawa Yasutomo , Tokunoh Ryosuke , Seki Tomohiro , Miyamoto Naoya , Sasaki Yusuke , Ohmiya Hirohisa
Published: October 2023

Chemical modification of nucleotides can improve the metabolic stability and target specificity of oligonucleotide therapeutics, and alkylphosphonates have been employed as charge-neutral replacements for naturally-occurring phosphodiester backbones in these compounds. However, at present, the alkyl moieties that can be attached to phosphorus atoms in these compounds are limited to methyl groups or primary/secondary alkyls, and such alkylphosphonate moieties can degrade during oligonucleotide synthesis. The present work demonstrates the tertiary alkylation of the phosphorus atoms of phosphites bearing two 2’-deoxynuclosides. This process utilizes a carbocation generated via a light-driven radical-polar crossover mechanism. This protocol provides tertiary alkylphosphonate structures that are difficult to synthesize using existing methods. The conversion of these species to oligonucleotides having charge-neutral alkylphosphonate linkages through a phosphoramidite-based approach was also confirmed in this study.
Remodeling the cellular stress response for enhanced genetic code expansion in mammalian cells
Authors: Sushkin Mikhail E. , Koehler Christine , Lemke Edward A.
Published: October 2023

Genetic code expansion (GCE) reprograms the translational machinery to site-specifically incorporate noncanonical amino acids (ncAAs) into a selected protein. The efficiency of GCE in mammalian cells might be compromised by cellular stress responses, among which, the protein kinase R(PKR)-dependent eIF2α phosphorylation pathway can reduce translation rates. Here we test several strategies to engineer the eIF2α pathway and boost the rate of translation and show that such interventions increase GCE efficiency in mammalian cells. In particular, addition of the N-terminal PKR fragment (1–174) provides a substantial enhancement in cytoplasmic GCE and also in GCE realized by OTOs (orthogonally translating designer organelles), which built on the principle of 2D phase separation to enable mRNA-selective ncAA incorporation. Our study demonstrates an approach for improving the efficiency of GCE and provides a means by which the power of designer organelles can be further optimized to tune protein translation.
Nickel-catalyzed acylzincation of allenes with organozincs and CO
Authors: Wu Xianqing , Wang Chenglong , Liu Ning , Qu Jingping , Chen Yifeng
Published: October 2023

Transition metal-catalyzed carbonylative reaction with CO gas are among the central task in organic synthesis, enabling the construction of highly valuable carbonyl compound. Here, we show an earth-abundant nickel-catalyzed three-component tandem acylzincation/cyclization sequence of allene and alkylzinc reagent with 1 atm of CO under mild conditions. This protocol is featured by broad functional group tolerance with high reaction selectivity, providing a rapid and convenient synthetic method for the construction of diverse fully substituted benzotropone derivatives. Mechanistic studies reveal that the installation of a cyano group tethered to allene moiety enables the high regio- and stereoselectivity of this acylzincation of allene, allowing the selective formation of three consecutive C-C bonds in a highly efficient manner.
An in situ dual-anchoring strategy for enhanced immobilization of PD-L1 to treat autoimmune diseases
Authors: Wang Shenqiang , Zhang Ying , Wang Yanfang , Yang Yinxian , Zhao Sheng , Sheng Tao , Zhang Yuqi , Gu Zhen , Wang Jinqiang , Yu Jicheng
Published: October 2023

Immune checkpoints play key roles in maintaining self-tolerance. Targeted potentiation of the checkpoint molecule PD-L1 through in situ manipulation offers clinical promise for patients with autoimmune diseases. However, the therapeutic effects of these approaches are often compromised by limited specificity and inadequate expression. Here, we report a two-step dual-anchor coupling strategy for enhanced immobilization of PD-L1 on target endogenous cells by integrating bioorthogonal chemistry and physical insertion of the cell membrane. In both type 1 diabetes and rheumatoid arthritis mouse models, we demonstrate that this approach leads to elevated and sustained conjugation of PD-L1 on target cells, resulting in significant suppression of autoreactive immune cell activation, recruitment of regulatory T cells, and systematic reshaping of the immune environment. Furthermore, it restores glucose homeostasis in type 1 diabetic mice for over 100 days. This specific in situ bioengineering approach potentiates the functions of PD-L1 and represents its translational potential.
Prognosis of recurrence after complete resection in early-stage lung adenocarcinoma based on molecular alterations: a systematic review and meta-analysis
Authors: Zhou Chu , Jing Zhongying , Liu Wei , Ma Zihuan , Liu Siyao , Fang Yueyu
Published: October 2023

Molecular biomarkers have the potential to predict the recurrence risk of early-stage lung adenocarcinoma (LUAD) after complete resection, but the study results are controversial. We aimed to clarify the association of molecular alterations with disease-free survival (DFS) and recurrence-free survival (RFS) in early-stage LUAD with R0 resection. Comprehensive searches were conducted in PubMed/MEDLINE, Web of Science, and Cochrane Library for this systematic review and meta-analysis with date restrictions from 2012 to 2022. In the 18 included studies, data from a total of 7417 participants in 11 studies and 4167 participants in 9 studies were collected for the EGFR and KRAS meta-analyses, respectively. Two studies were assessed as having a moderate risk of bias, and the others were all assessed as having a high individual risk of bias. The molecular alterations in KRAS rather than EGFR, were associated with a high risk of recurrence for early-stage LUAD patients suffering from R0 resection, especially for those in pStage I, the pooled hazard ratios (HRs) of KRAS were 2.71 (95% CI, 1.81–4.06; I2 = 22%; P < 0.00001) and 1.95 (95% CI, 1.25–3.20; I2 = 57%; P = 0.003) with small interstudy heterogeneity in univariate and multivariate analyses, respectively. This finding suggests that molecular alterations in KRAS that could be detected by polymerase chain reaction techniques would provide new insight into stratifying risk and personalizing patient postoperative follow-up.
GPU-acceleration of the distributed-memory database peptide search of mass spectrometry data
Authors: Haseeb Muhammad , Saeed Fahad
Published: October 2023

Database peptide search is the primary computational technique for identifying peptides from the mass spectrometry (MS) data. Graphical Processing Units (GPU) computing is now ubiquitous in the current-generation of high-performance computing (HPC) systems, yet its application in the database peptide search domain remains limited. Part of the reason is the use of sub-optimal algorithms in the existing GPU-accelerated methods resulting in significantly inefficient hardware utilization. In this paper, we design and implement a new-age CPU-GPU HPC framework, called GiCOPS, for efficient and complete GPU-acceleration of the modern database peptide search algorithms on supercomputers. Our experimentation shows that the GiCOPS exhibits between 1.2 to 5$$\times$$
×
speed improvement over its CPU-only predecessor, HiCOPS, and over 10$$\times$$
×
improvement over several existing GPU-based database search algorithms for sufficiently large experiment sizes. We further assess and optimize the performance of our framework using the Roofline Model and report near-optimal results for several metrics including computations per second, occupancy rate, memory workload, branch efficiency and shared memory performance. Finally, the CPU-GPU methods and optimizations proposed in our work for complex integer- and memory-bounded algorithmic pipelines can also be extended to accelerate the existing and future peptide identification algorithms. GiCOPS is now integrated with our umbrella HPC framework HiCOPS and is available at: https://github.com/pcdslab/gicops.
Pyrethroid insecticides susceptibility profiles and evaluation of L1014F kdr mutant alleles in Culex quinquefasciatus from lymphatic filariasis endemic communities
Authors: Okafor Martina Anurika , Ekpo Ndifreke Daniel , Opara Kenneth Nnamdi , Udoidung Nsima Ibanga , Ataya Farid S. , Yaro Clement Ameh , Batiha Gaber El-Saber , Alexiou Athanasios , Papadakis Marios
Published: October 2023

This study investigated the dynamics in pyrethriod resistance and the presence/frequencies of L1014F knockdown resistance mutant allelles in Culex quinquefasciatus vector populations from Uruan Local Government Area of AkwaIbom State, Southern Nigeria between the months of March and November, 2021. Uruan LGA is among the endemic LGAs for lymphatic filariasis in AkwaIbomState. Female Anopheles mosquitoes from Eman Uruan, Ituk Mbang and Idu Uruan were exposed to permethrin, deltamethrin and alphacypermethrin in CDC insecticide coated bottles for susceptibility bioassay following standard protocols. The mosquitoes were obtained as aquatic forms from the study sites and reared under laboratory conditions to adults. The adult mosquitoes were used for this study. All the mosquitoes used for the insecticide susceptibility bioassay were morphologically identified. Standard Polymerase chain reaction (PCR) was used for authenticating the Culex quinquefasciatus species. A portion of the vgsc (917 bp) gene spanning the entire intron and the exon containing the L1014F mutation associated with knockdown resistance (kdr) in the vectorswere amplified using Allele-SPECIFIC POLYMERASE CHAIN REACTION (AS-PCR) in order to detect target site insensitivity in the vectors from the study sites. Results obtained revealed that vectors from all the study sites were resistant to permethrin insecticide (mortality rate: 18–23%). Suspected resistance (mortality rate: 90–93%) to deltamethrin and low resistance (mortality rate: 82–85%) to alphacypermethrin insecticides were detected. knockdown was more rapid with deltamethrin and alphacypermethrin than with permethrin across the study sites considering their KDT50 and KDT95. The frequency of the resistant phenotypes ranged from 35.14 to 55.3% across the study sites with a net of 45.1% resistant phenotype recorded in this study. The 1014F allelic frequency calculated from Hardy–Weinberg principle for vector populations across the study sites ranged from 0.500 (50.00%) to 0.7763 (77.63%). All populations witnessed significant (p < 0.05) deviations from Hardy–Weinberg equilibrium in the distribution of these alleles. The findings of this study show that there is a tendency to record an entire population of resistant vectors in this study area over time due to natural selection. The public health implication of these findings is that the use of pyrethroid based aerosols, coils, sprays, LLITNs and others for the purpose of controlling vectors of lymphatic filariasis and other diseases may be effort in futility.
Genome-wide identification and expression analysis of the GRAS gene family under abiotic stresses in wheat (Triticum aestivum L.)
Authors: Mishra Shefali , Chaudhary Reeti , Pandey Bharti , Singh Gyanendra , Sharma Pradeep
Published: October 2023

The GRAS transcription factors are multifunctional proteins involved in various biological processes, encompassing plant growth, metabolism, and responses to both abiotic and biotic stresses. Wheat is an important cereal crop cultivated worldwide. However, no systematic study of the GRAS gene family and their functions under heat, drought, and salt stress tolerance and molecular dynamics modeling in wheat has been reported. In the present study, we identified the GRAS gene in Triticum aestivum through systematically performing gene structure analysis, chromosomal location, conserved motif, phylogenetic relationship, and expression patterns. A total of 177 GRAS genes were identified within the wheat genome. Based on phylogenetic analysis, these genes were categorically placed into 14 distinct subfamilies. Detailed analysis of the genetic architecture revealed that the majority of TaGRAS genes had no intronic regions. The expansion of the wheat GRAS gene family was proven to be influenced by both segmental and tandem duplication events. The study of collinearity events between TaGRAS and analogous orthologs from other plant species provided valuable insights into the evolution of the GRAS gene family in wheat. It is noteworthy that the promoter regions of TaGRAS genes consistently displayed an array of cis-acting elements that are associated with stress responses and hormone regulation. Additionally, we discovered 14 miRNAs that target key genes involved in three stress-responsive pathways in our study. Moreover, an assessment of RNA-seq data and qRT-PCR results revealed a significant increase in the expression of TaGRAS genes during abiotic stress. These findings highlight the crucial role of TaGRAS genes in mediating responses to different environmental stresses. Our research delved into the molecular dynamics and structural aspects of GRAS domain-DNA interactions, marking the first instance of such information being generated. Overall, the current findings contribute to our understanding of the organization of the GRAS genes in the wheat genome. Furthermore, we identified TaGRAS27 as a candidate gene for functional research, and to improve abiotic stress tolerance in the wheat by molecular breeding.