bluuebunny/crossref_metadata_2025 huggingface dataset:
A multigenerational study on phenotypic consequences of the most common causal variant of HNF1A-MODY
Authors: Kettunen Jarno L. T. , Rantala Elina , Dwivedi Om P. , Isomaa Bo , Sarelin Leena , Kokko Paula , Hakaste Liisa , Miettinen Päivi J. , Groop Leif C. , Tuomi Tiinamaija
Published: December 2021

Aims/hypothesis

Systematic studies on the phenotypic consequences of variants causal of HNF1A-MODY are rare. Our aim was to assess the phenotype of carriers of a single HNF1A variant and genetic and clinical factors affecting the clinical spectrum.

Methods

We conducted a family-based multigenerational study by comparing heterozygous carriers of the HNF1A p.(Gly292fs) variant with the non-carrier relatives irrespective of diabetes status. During more than two decades, 145 carriers and 131 non-carriers from 12 families participated in the study, and 208 underwent an OGTT at least once. We assessed the polygenic risk score for type 2 diabetes, age at onset of diabetes and measures of body composition, as well as plasma glucose, serum insulin, proinsulin, C-peptide, glucagon and NEFA response during the OGTT.

Results

Half of the carriers remained free of diabetes at 23 years, one-third at 33 years and 13% even at 50 years. The median age at diagnosis was 21 years (IQR 17–35). We could not identify clinical factors affecting the age at conversion; sex, BMI, insulin sensitivity or parental carrier status had no significant effect. However, for 1 SD unit increase of a polygenic risk score for type 2 diabetes, the predicted age at diagnosis decreased by 3.2 years. During the OGTT, the carriers had higher levels of plasma glucose and lower levels of serum insulin and C-peptide than the non-carriers. The carriers were also leaner than the non-carriers (by 5.0 kg, p=0.012, and by 2.1 kg/m2 units of BMI, p=2.2 × 10−4, using the first adult measurements) and, possibly as a result of insulin deficiency, demonstrated higher lipolytic activity (with medians of NEFA at fasting 621 vs 441 μmol/l, p=0.0039; at 120 min during an OGTT 117 vs 64 μmol/l, p=3.1 × 10−5).

Conclusions/interpretation

The most common causal variant of HNF1A-MODY, p.(Gly292fs), presents not only with hyperglycaemia and insulin deficiency, but also with increased lipolysis and markedly lower adult BMI. Serum insulin was more discriminative than C-peptide between carriers and non-carriers. A considerable proportion of carriers develop diabetes after young adulthood. Even among individuals with a monogenic form of diabetes, polygenic risk of diabetes modifies the age at onset of diabetes.

Graphical abstract
The C50 carotenoid bacterioruberin regulates membrane fluidity in pink-pigmented Arthrobacter species
Authors: Flegler Alexander , Lipski André
Published: December 2021

Carotenoids have several crucial biological functions and are part of the cold adaptation mechanism of some bacteria. Some pink-pigmented Arthrobacter species produce the rare C50 carotenoid bacterioruberin, whose function in these bacteria is unclear and is found mainly in halophilic archaea. Strains Arthrobacter agilis DSM 20550T and Arthrobacter bussei DSM 109896T show an increased bacterioruberin content if growth temperature is reduced from 30 down to 10 °C. In vivo anisotropy measurements with trimethylammonium-diphenylhexatriene showed increased membrane fluidity and a broadening phase transition with increased bacterioruberin content in the membrane at low-temperature growth. Suppression of bacterioruberin synthesis at 10 °C using sodium chloride confirmed the function of bacterioruberin in modulating membrane fluidity. Increased bacterioruberin content also correlated with increased cell resistance to freeze–thaw stress. These findings confirmed the adaptive function of bacterioruberin for growth at low temperatures for pink-pigmented Arthrobacter species.
Campana points and powerful values of norm forms
Authors: Streeter Sam
Published: December 2021

We give an asymptotic formula for the number of weak Campana points of bounded height on a family of orbifolds associated to norm forms for Galois extensions of number fields. From this formula we derive an asymptotic for the number of elements with m-full norm over a given Galois extension of $$\mathbb {Q}$$
Q
. We also provide an asymptotic for Campana points on these orbifolds which illustrates the vast difference between the two notions, and we compare this to the Manin-type conjecture of Pieropan, Smeets, Tanimoto and Várilly-Alvarado.
Associations do not energize behavior: on the forgotten legacy of Kurt Lewin
Authors: Eder Andreas B. , Dignath David
Published: December 2021

Hundred years ago, Kurt Lewin published a series of articles in which he vehemently argued against the idea that associations between stimuli and responses motivate behavior. This article reviews his empirical work and theory and the cogency of Lewin’s conclusion according to modern standards. We conclude that Lewin’s criticism of the contiguity principle of associationism is still valid, and is now supported by a broad range of theories on learning, motivation, and action control. Implications for modern dual-system theory and modern theories on motivated action and (instructed) task sets are discussed.
An alternative approach to estimate any subdaily extreme of rainfall and wind from usually available records
Authors: Pérez-Bella José M. , Domínguez-Hernández Javier , Martínez-Martínez Juan E. , Alonso-Martínez Mar , del Coz-Díaz Juan J.
Published: December 2021

A wide variety of engineering applications requires the use of maximum values of rainfall intensity and wind speed related to short recording intervals, which can often only be estimated from available less exhaustive records. Given that many locations lack exhaustive climatic records that would allow accurate empirical correlations between different recording intervals to be identified, generic equations are often used to estimate these extreme values. The accuracy of these generic estimates is especially important in fields such as the study of wind-driven rain, in which both climatic variables are combined to characterise the phenomenon. This work assesses the reliability and functionality of some of these most widespread generic equations, analysing climatic datasets gathered since 2008 in 109 weather stations in Spain and the Netherlands. Considering multiple recording intervals at each location, it is verified that most of these generic estimations, used especially in the study of wind-driven rain, have functional limitations and can cause significant errors when characterising both variables for subdaily intervals and extreme conditions. Finally, an alternative approach is proposed to accurately extrapolate extreme values of both variables related to any subdaily recording interval in a functional manner and from any available records.
A tutorial on reproducing a predefined autocovariance function through AR models: application to stationary homogeneous isotropic turbulence
Authors: Gallego-Castillo Cristobal , Cuerva-Tejero Alvaro , Elagamy Mohanad , Lopez-Garcia Oscar , Avila-Sanchez Sergio
Published: December 2021

Sequential methods for synthetic realisation of random processes have a number of advantages compared with spectral methods. In this article, the determination of optimal autoregressive (AR) models for reproducing a predefined target autocovariance function of a random process is addressed. To this end, a novel formulation of the problem is developed. This formulation is linear and generalises the well-known Yule-Walker (Y-W) equations and a recent approach based on restricted AR models (Krenk-Møller approach, K-M). Two main features characterise the introduced formulation: (i) flexibility in the choice for the autocovariance equations employed in the model determination, and (ii) flexibility in the definition of the AR model scheme. Both features were exploited by a genetic algorithm to obtain optimal AR models for the particular case of synthetic generation of homogeneous stationary isotropic turbulence time series. The obtained models improved those obtained with the Y-W and K-M approaches for the same model parsimony in terms of the global fitting of the target autocovariance function. Implications for the reproduced spectra are also discussed. The formulation for the multivariate case is also presented, highlighting the causes behind some computational bottlenecks.
The westernmost Late Miocene–Pliocene volcanic activity in the Vardar zone (North Macedonia)
Authors: Molnár Kata , Lahitte Pierre , Dibacto Stéphane , Benkó Zsolt , Agostini Samuele , Döncző Boglárka , Ionescu Artur , Milevski Ivica , Szikszai Zita , Kertész Zsófia , Temovski Marjan
Published: December 2021

Late Miocene to Pleistocene volcanism within the Vardar zone (North Macedonia) covers a large area, has a wide range in composition, and is largely connected to the tectonic evolution of the South Balkan extensional system, the northern part of the Aegean extensional regime. The onset of the scattered potassic to ultrapotassic volcanism south from the Scutari-Peć transverse zone occurred at ca. 8.0 Ma based on this study. Here, we focused on three volcanic centers located on deep structures or thrust faults along the western part of the Vardar zone, for which there is none to very little geochronological and geochemical data available. Pakoševo and Debrište localities are represented as small remnants of lava flows cropping out at the southern edge of Skopje basin and at the western edge of Tikveš basin, respectively. Šumovit Greben center is considered as part of the Kožuf-Voras volcanic system, and it is located on its westernmost side, at the southern edge of Mariovo basin, which is largely composed of volcaniclastic sediments. We present new eruption ages applying the unspiked Cassignol-Gillot K–Ar technique on groundmass, as well as petrological and geochemical data, supplemented with Sr and Nd isotopes to complement and better understand the Neogene-Pleistocene volcanism in the region. Eruption ages on these rocks interlayered between sedimentary formations allow to better constrain the evolution of those sedimentary basins. Rocks from the three volcanic centers belong to the high-K calc-alkaline–shoshonitic series based on their elevated K content. The oldest center amongst these three localities, as well as other Late Miocene centers within the region, is the trachyandesitic Debrište, which formed at ca. 8.0 Ma, and exhibits the highest Nd and lowest Sr isotopic ratios (0.512441–0.512535 and 0.706759–0.706753, respectively). The basaltic trachyandesite Pakoševo center formed at ca. 3.8 Ma and its Nd and Sr isotopic ratios (0.512260 and 0.709593, respectively) bear the strongest signature of crustal contamination. The rhyolitic Šumovit Greben center is a composite volcanic structure formed at ca. 3.0–2.7 Ma. Its youngest eruption unit has a slightly higher Nd and lower Sr isotopic ratios (0.512382 and 0.709208, respectively) representing a magma with a lesser extent of crustal assimilation than the other samples from this center. The overall trend through time in the Sr and Nd isotopic ratios of the Late Miocene to Pleistocene mafic volcanic centers in the region implies an increasing rate of metasomatism of the lithospheric mantle.
Buddhist entrepreneurs, charitable behaviors, and social entrepreneurship: evidence from China
Authors: Xu Zuhui , Liu Zhiyang , Wu Jie
Published: December 2021

To address the lacuna of how informal institutions like Buddhism impact social entrepreneurship in different regions within a nation, this research draws on the social entrepreneurship literature and the regional Buddhist research to propose a mediating framework where the percentage of Buddhist entrepreneurs in a region is positively associated both with the level of prosocial behaviors such as charity, due to the values of Buddhism, and with the probability of establishing businesses in a less-developed region. It further proposes that charitable behaviors mediate the relationship between the percentage of Buddhist entrepreneurs in a region and establishing businesses in less-developed regions. This mediating effect is attributed to the mechanism that charitable behaviors absorb the limited resources of entrepreneurs, reducing their resources for establishing businesses in less-developed regions. We test these hypotheses on nationwide surveys of founders of private enterprises and find support for this mediating view. Broad implications for theoretical and empirical research are discussed.
Best Reply Player Against Mixed Evolutionarily Stable Strategy User
Authors: Garay József , Móri Tamás F.
Published: December 2021

We consider matrix games with two phenotypes (players): one following a mixed evolutionarily stable strategy and another one that always plays a best reply against the action played by its opponent in the previous round (best reply player, BR). We focus on iterated games and well-mixed games with repetition (that is, the mean number of repetitions is positive, but not infinite). In both interaction schemes, there are conditions on the payoff matrix guaranteeing that the best reply player can replace the mixed ESS player. This is possible because best reply players in pairs, individually following their own selfish strategies, develop cycles where the bigger payoff can compensate their disadvantage compared with the ESS players. Well-mixed interaction is one of the basic assumptions of classical evolutionary matrix game theory. However, if the players repeat the game with certain probability, then they can react to their opponents’ behavior. Our main result is that the classical mixed ESS loses its general stability in the well-mixed population games with repetition in the sense that it can happen to be overrun by the BR player.
Vector Symbolic Architectures for Context-Free Grammars
Authors: Graben Peter beim , Huber Markus , Meyer Werner , Römer Ronald , Wolff Matthias
Published: December 2021

Vector symbolic architectures (VSA) are a viable approach for the hyperdimensional representation of symbolic data, such as documents, syntactic structures, or semantic frames. We present a rigorous mathematical framework for the representation of phrase structure trees and parse trees of context-free grammars (CFG) in Fock space, i.e. infinite-dimensional Hilbert space as being used in quantum field theory. We define a novel normal form for CFG by means of term algebras. Using a recently developed software toolbox, called FockBox, we construct Fock space representations for the trees built up by a CFG left-corner (LC) parser. We prove a universal representation theorem for CFG term algebras in Fock space and illustrate our findings through a low-dimensional principal component projection of the LC parser state. Our approach could leverage the development of VSA for explainable artificial intelligence (XAI) by means of hyperdimensional deep neural computation.
Evaluation of the aerodynamic performance of the counter rotating turbo fan COBRA by means of experimental and numerical data
Authors: Ly Thibault , Koc Kazim , Meillard Lionel , Schnell Rainer
Published: December 2021

In the present study, steady numerical simulations performed on the counter rotating turbo fan (CRTF) COBRA are compared with experimental data carried at the CIAM C-3A test-bench in Moscow. For this purpose, a systematic analysis of the measurement uncertainties was performed for the global aerodynamic performances of the CRTF, namely, the massflow, the total pressure ratio, the isentropic efficiency, as well as the torque ratio applied on both fan rows. Several numerical models are investigated to highlight their effects on the aforementioned predicted quantities. Differences in modeling consist in grid resolutions and the use of two turbulence models popular in the turbomachinery community. To match as much as possible the experiment running conditions, the performance map of the CRTF is simulated using the exact measured speed ratio and massflow. The comparisons show good estimations of the numerical simulation over the entire performance map. The main differences between the turbulence models occur at part-speed close to stall conditions. More surprisingly at aerodynamic design point, the importance of the turbulence modeling on the predicted torque ratio has been pointed out.
High piezoelectricity after field cooling AC poling in temperature stable ternary single crystals manufactured by continuous-feeding Bridgman method
Authors: Luo Cong , Karaki Tomoaki , Wang Zhuangkai , Sun Yiqin , Yamashita Yohachi , Xu Jiayue
Published: December 2021

After field cooling (FC) alternating current poling (ACP), we investigated the dielectric and piezoelectric properties of [001]pc-oriented 0.24Pb(In1/2Nb1/2)O3 (PIN)-0.46Pb(Mg1/3Nb2/3)O3 (PMN)-0.30PbTiO3 (PT) (PIMN-0.30PT) single crystals (SCs), which were manufactured by continuous-feeding Bridgman (CF BM) within morphotropic phase boundary (MPB) region. By ACP with 4 kVrms/cm from 100 to 70 °C, the PIMN-0.30PT SC attained high dielectric permittivity (ε33T/ε0) of 8330, piezoelectric coefficient (d33) of 2750 pC/N, bar mode electromechanical coupling factor k33 of 0.96 with higher phase change temperature (Tpc) of 103 °C, and high Curie temperature (TC) of 180 °C. These values are the highest ever reported as PIMN-xPT SC system with Tpc > 100 °C. The enhancement of these properties is attributed to the induced low symmetry multi-phase supported by phase analysis. This work indicates that FC ACP is a smart and promising method to enhance piezoelectric properties of relaxor-PT ferroelectric SCs including PIMN-xPT, and provides a route to a wide range of piezoelectric device applications.
Advances in ultra-high temperature ceramics, composites, and coatings
Authors: Ni Dewei , Cheng Yuan , Zhang Jiaping , Liu Ji-Xuan , Zou Ji , Chen Bowen , Wu Haoyang , Li Hejun , Dong Shaoming , Han Jiecai , Zhang Xinghong , Fu Qiangang , Zhang Guo-Jun
Published: December 2021

Ultra-high temperature ceramics (UHTCs) are generally referred to the carbides, nitrides, and borides of the transition metals, with the Group IVB compounds (Zr & Hf) and TaC as the main focus. The UHTCs are endowed with ultra-high melting points, excellent mechanical properties, and ablation resistance at elevated temperatures. These unique combinations of properties make them promising materials for extremely environmental structural applications in rocket and hypersonic vehicles, particularly nozzles, leading edges, and engine components, etc. In addition to bulk UHTCs, UHTC coatings and fiber reinforced UHTC composites are extensively developed and applied to avoid the intrinsic brittleness and poor thermal shock resistance of bulk ceramics. Recently, highentropy UHTCs are developed rapidly and attract a lot of attention as an emerging direction for ultra-high temperature materials. This review presents the state of the art of processing approaches, microstructure design and properties of UHTCs from bulk materials to composites and coatings, as well as the future directions.
Conspiracy theories on Twitter: emerging motifs and temporal dynamics during the COVID-19 pandemic
Authors: Batzdorfer Veronika , Steinmetz Holger , Biella Marco , Alizadeh Meysam
Published: December 2021

The COVID-19 pandemic resulted in an upsurge in the spread of diverse conspiracy theories (CTs) with real-life impact. However, the dynamics of user engagement remain under-researched. In the present study, we leverage Twitter data across 11 months in 2020 from the timelines of 109 CT posters and a comparison group (non-CT group) of equal size. Within this approach, we used word embeddings to distinguish non-CT content from CT-related content as well as analysed which element of CT content emerged in the pandemic. Subsequently, we applied time series analyses on the aggregate and individual level to investigate whether there is a difference between CT posters and non-CT posters in non-CT tweets as well as the temporal dynamics of CT tweets. In this regard, we provide a description of the aggregate and individual series, conducted a STL decomposition in trends, seasons, and errors, as well as an autocorrelation analysis, and applied generalised additive mixed models to analyse nonlinear trends and their differences across users. The narrative motifs, characterised by word embeddings, address pandemic-specific motifs alongside broader motifs and can be related to several psychological needs (epistemic, existential, or social). Overall, the comparison of the CT group and non-CT group showed a substantially higher level of overall COVID-19-related tweets in the non-CT group and higher level of random fluctuations. Focussing on conspiracy tweets, we found a slight positive trend but, more importantly, an increase in users in 2020. Moreover, the aggregate series of CT content revealed two breaks in 2020 and a significant albeit weak positive trend since June. On the individual level, the series showed strong differences in temporal dynamics and a high degree of randomness and day-specific sensitivity. The results stress the importance of Twitter as a means of communication during the pandemic and illustrate that these beliefs travel very fast and are quickly endorsed.
Improving membrane filtration performance through time series analysis
Authors: Wu Jun Jie
Published: December 2021

For ultrafiltration, and membrane filtration more generally, the quantitative determination of the modes of fouling remains a subject of great interest. Herein an integral method for determining the modes from a time series of volumetric flux $$J\left(t\right)$$

J

t

is given and illustrated with previously published filtration data of bergamot juice (Ruby-Figueroa et al (J Membr Sci 524:108-116, 2017)). The integral method of fouling analysis has the potential to become the cornerstone of a robust empirical process. In addition to determining, in a clear-cut manner, the point at which there is a switch from one mode to another, the robust methodology yields characteristic $$J\left(t\right)$$

J

t

equation for each mode that are an excellent fit to the data. The emphasis is upon the creation of a robust methodology which is best viewed as being a semi-empirical method that is indicative of the modes of fouling. For the example chosen, the initial 4 L/m2 generates some pore blocking after which the main mode of fouling is cake build-up. The variation of overall resistance with time is also informative and analysis of this series was used to check the result for the initial phase of fouling as determined from the time series of volumetric flux. A comparison against the ARIMA (Autoregressive integrated moving average) method, which has never been previously undertaken, is given herein. The integral method of fouling analysis was found to be superior, in part because of the quality of fit to the data and in part because it enables one to establish whether the initial fouling is different in character from the subsequent fouling. Having this information can improve membrane selection and overall membrane filtration performance.
The Printing and the Printers of The Book of Common Prayer, 1549–1561
Authors: Blayney Peter W. M.
Published: December 2021

Bibliographers have been notoriously 'hesitant to deal with liturgies', and this volume bridges an important gap with its authoritative examination of how the Book of Common Prayer came into being. The first edition of 1549, the first Grafton edition of 1552 and the first quarto edition of 1559 are now correctly identified, while Peter W. M. Blayney shows that the first two editions of 1559 were probably finished on the same day. Through relentless scrutiny of the evidence, he reveals that the contents of the 1549 version continued to evolve both during and after the printing of the first edition, and that changes were still being made to the Elizabethan revision weeks after the Act of Uniformity was passed. His bold reconstruction is transformative for the early Anglican liturgy, and thus for the wider history of the Church of England. This major, revisionist work is a remarkable book about a remarkable book.
Colonial Petitions, Colonial Petitioners, and the Imperial Parliament, ca. 1780–1918
Authors: Huzzey Richard , Miller Henry
Published: December 2021

Petitioning was a common form of protest, request, or expression across the British Empire, and historians of colonial rule and resistance have often drawn on petitions as sources to investigate particular controversies. This article assesses the significance, variety, and context of petitioning to the Imperial Parliament from both the British Isles and the colonies. To do so, we present new data drawn from more than one million petitions sent to the House of Commons in the period from 1780 to 1918, alongside qualitative research into a wider range of petitions to other metropolitan sources of authority. This range permits us to assess how colonial subjects across the empire demanded attention from Westminster and what the practice of petitioning reveals about the British self-image of parliamentary scrutiny and equality before the law.
Student and teacher perceptions of the value of Total War: Saga in motivating KS3 students in an all-boys state school
Authors: Cannatella Pietro
Published: December 2021

This paper will investigate the efficacy of using game-based learning to increase motivation in Key Stage 3 boys (aged 11–14) at a single-sex, non-selective free school located in inner London. During observations of classes I have seen a spectrum of varying motivation in the classroom. As such, the aim of this game-inspired motivation should, as this paper will find, have a clearly demonstrable influence on their academic studies. This will be examined through measuring both an increase in intercultural communication competence and a desire to autodidactically research these historical and classical topics. Whilst the long-term effects of this research paper on its participants will not be properly understood for years to come, what can be currently measured, I hope, can offer genuine excitement in the area of digital games and motivation.
Temperatures of the Lacus Mortis Region of the Moon
Authors: Williams Jean‐Pierre , Greenhagen Benjamin T. , Bennett Kristen A. , Paige David A. , Kumari Nandita , Ahrens Caitlin J. , Rubanenko Lior , Powell Tyler M. , Prem Parvathy , Blewett David T. , Russell Patrick S. , Hayne Paul O. , Sullivan Mark T.
Published: December 2021

Over 11 years of data acquired by the Diviner Lunar Radiometer Experiment instrument aboard Lunar Reconnaissance Orbiter have been compiled into a comprehensive data set of surface temperatures in the Lacus Mortis region which includes the landing ellipse of the Astrobotic Mission One lander mission. These data provide diurnal brightness temperatures at 128 pixels per degree (ppd) spatial resolution and 0.1 hr of local time resolution. From this data set, we highlight several features that display variations in radiative and thermophysical properties in the Lacus Mortis region and characterize the temperatures of the Astrobotic Mission One landing ellipse. We identify distinctly contrasting properties of materials in the walls of Bürg crater, hummocks of materials on the southeast margin of the mare basalts, and materials exposed or excavated by impacts. Additionally, we describe an exceptionally rocky fault scarp that predates the formation of Bürg crater suggesting the observed boulders are replenished on a timescale <1 Ga. Within the Astrobotic landing ellipse, temperatures are observed to range from ∼88 to ∼359 K with sunrise and sunset local times constrained to 5.8–6.3 hr and 17.8 and 18.1 hr respectively.
Proton Temperature Anisotropies in the Venus Plasma Environment During Solar Minimum and Maximum
Authors: Rojas Mata Sebastián , Stenberg Wieser Gabriella , Futaana Yoshifumi , Bader Alexander , Persson Moa , Fedorov Andrey , Zhang Tielong
Published: December 2021

The proton population in Venus' plasma environment is characterized during periods of solar minimum and maximum using data from a particle mass‐energy spectrometer. Such characterizations at different levels of solar activity provides physical insight into solar‐cycle‐dependent plasma phenomena around the planet, for example mirror modes in the magnetosheath. Statistical distributions of proton bulk speeds and temperatures are generated using a previously developed method which applies Maxwellian fits to measurements of the protons' velocity distribution function. Spatial maps and probability‐density histograms comparing the proton parameters between the two time periods are presented. The temperatures perpendicular (T⊥) and parallel (T∥) to the background magnetic field are found to be 20%–35% lower during solar maximum. Though the overall distributions of the temperature ratio T⊥/T∥ do not change, the regions with higher anisotropy (T⊥/T∥ > 1) are found farther downstream from the bow shock during solar maximum than minimum. This is consistent with the previously observed growth of mirror modes during solar maximum and their decay during minimum.
Spatial and Temporal Variability of Dissolved Organic Matter Molecular Composition in a Stratified Eutrophic Lake
Authors: Berg Stephanie M. , Peterson Benjamin D. , McMahon Katherine D. , Remucal Christina K.
Published: December 2021

Dissolved organic matter (DOM) is an intermediate between organic carbon formed by primary producers and carbon dioxide (CO2) produced through respiration, making it a key component of the carbon cycle in aquatic ecosystems. Its composition influences the routes of mineralization. Here, we evaluate DOM composition as a function of time and depth in Lake Mendota, a highly productive eutrophic lake that stratifies in warm months and is located in Madison, Wisconsin, USA. Dissolved organic carbon concentrations and optical properties are presented for 73 samples collected at a single location at varying depths within the water column from June to November. A subset of samples is analyzed by Fourier transform‐ion cyclotron resonance mass spectrometry (FT‐ICR MS) to investigate DOM composition at the molecular level. Temporally, increases in more oxidized formulas are observed in both the epilimnion and hypolimnion. At the surface, correlations between DOM formulas and both chlorophyll concentrations and light intensity show that photochemical reactions contribute to DOM oxidation. In the hypolimnion, redox conditions and interactions with sediments likely influence temporal compositional change. Our results show DOM composition varies with depth with more highly oxidized formulas identified deeper in the water column. However, DOM composition varies more temporally than by location within the water column. This work has implications for climate change as DOM photooxidation in lakes represents an understudied flux of CO2 to the atmosphere. Additionally, lake eutrophication is increasing due to warming temperatures and this data set yields detailed molecular information about DOM composition and processing in such lakes.
A Fast Monotone Discretization of the Rotating Shallow Water Equations
Authors: Roullet Guillaume , Gaillard Tugdual
Published: December 2021

This paper presents a new discretization of the rotating shallow water equations and a set of decisions, ranging from a simplification of the continuous equations down to the implementation level, yielding a code that is fast and accurate. Accuracy is reached by using WENO reconstructions on the mass flux and on the nonlinear Coriolis term. The results show that the implicit mixing and dissipation, provided by the discretization, allow a very good material conservation of potential vorticity and a minimal energy dissipation. Numerical experiments are presented to assess the accuracy, which include a resolution convergence, a sensitivity on the free‐slip versus no‐slip boundary conditions, a study on the separation of waves from vortical motions. Speed is achieved by a series of choices rather than a single recipe. The main choice is to discretize the covariant form written in index coordinates. This form, rooted in the discrete differential geometry, removes most of the grid scale terms from the equations, and keeps them only where they should be. The model objects appearing in resulting continuous equations have a natural correspondence with the grid cell features. The other choices are guided by the maximization of the arithmetic intensity. Finally this paper also proves that a pure Python implementation can be very fast, thanks to the possibility of having compiled Python. As a result, the code performs 2 TFlops per second using thousand cores.
Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human ACE2-transgenic mice
Authors: Bi Zhenfei , Hong Weiqi , Que Haiying , He Cai , Ren Wenyan , Yang Jingyun , Lu Tianqi , Chen Li , Lu Shuaiyao , Peng Xiaozhong , Wei Xiawei
Published: December 2021

The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening. Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2, which greatly limits its application in routine research. Here, we generate a mouse model of COVID-19 under a general laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) observed in humans. Briefly, human ACE2-transgenic (hACE2) mice were intratracheally instilled with the formaldehyde-inactivated SARS-CoV-2, resulting in a rapid weight loss and detrimental changes in lung structure and function. The pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation, hemorrhage, necrotic debris, and hyaline membrane formation. The production of fatal cytokines (IL-1β, TNF-α, and IL-6) and the infiltration of activated neutrophils, inflammatory monocyte-macrophages, and T cells in the lung were also determined, suggesting the activation of an adaptive immune response. Therapeutic strategies, such as dexamethasone or passive antibody therapy, could effectively ameliorate the disease progression in this model. Therefore, the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS.
Long-term stability and protection efficacy of the RBD-targeting COVID-19 mRNA vaccine in nonhuman primates
Authors: Zhao Hui , Wang Tie-Cheng , Li Xiao-Feng , Zhang Na-Na , Li Liang , Zhou Chao , Deng Yong-Qiang , Cao Tian-Shu , Yang Guan , Li Rui-Ting , Huang Yi-Jiao , Li Yuan-Guo , Zhang Yi-Ming , Li Fang-Xu , Zhou Yu-Ren , Jiang Yu-Hang , Lu Xi-Shan , Sun Shi-Hui , Cheng Meng-Li , Gu Kai-Ping , Zhang Mei , Ma Qing-Qing , Yang Xiao , Ying Bo , Gao Yu-Wei , Qin Cheng-Feng
Published: December 2021

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2–8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.
Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients
Authors: Bethge Wolfgang A. , Eyrich Matthias , Mielke Stephan , Meisel Roland , Niederwieser Dietger , Schlegel Paul G. , Schulz Ansgar , Greil Johann , Bunjes Donald , Brecht Arne , Kuball Jurgen , Schumm Michael , Vucinic Vladan , Wiesneth Markus , Bonig Halvard , Westinga Kasper , Biedermann Stefanie , Holtkamp Silke , Karitzky Sandra , Malchow Michaela , Siewert Christiane , Handgretinger Rupert , Lang Peter
Published: December 2021

Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αβ/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 106 CD34+ cells/kg and 14.2 × 103 TCRαβ+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαβ/CD19-depleted grafts represents a viable treatment option.
Emergence of the topological Hall effect in a tetragonal compensated ferrimagnet Mn2.3Pd0.7Ga
Authors: Choi Won-Young , Yoo Woosuk , Jung Myung-Hwa
Published: December 2021

Topological spin textures such as magnetic skyrmions have attracted considerable interest due to their potential application in spintronic devices. However, there still remain several challenges to overcome before their practical application, for instance, achieving high scalability and thermal stability. Recent experiments have proposed a new class of skyrmion materials in the Heusler family, Mn1.4Pt0.9Pd0.1Sn and Mn2Rh0.95Ir0.05Sn, which possess noncollinear magnetic structures. Motivated by these experimental results, we suggest another Heusler compound hosted by Mn3Ga to overcome the above limitations. We fabricate Mn3-xPdxGa thin films, focusing on the magnetic compensation point. In Mn2.3Pd0.7Ga, we find a spin-reorientation transition around TSR = 320 K. Below the TSR, we observe the topological Hall effect and a positive magnetic entropy change, which are the hallmarks of a chiral noncollinear spin texture. By integrating all the data, we determine the magnetic phase diagram, displaying a wide chiral noncollinear spin phase even at room temperature. We believe that this compensated ferrimagnet shows promise for opening a new avenue toward chiral spin-based, high-density, and low-power devices.
A case report of COVID-19 monitoring in the Austrian professional football league
Authors: van der Zee-Neuen Antje , Schaffler-Schaden Dagmar , Herfert Jürgen , O´Brien James , Johansson Tim , Kutschar Patrick , Seymer Alexander , Ludwig Stephan , Stöggl Thomas , Keeley David , Resch Herbert , Osterbrink Jürgen , Flamm Maria
Published: December 2021

Since the beginning of the COVID -19 pandemic, many contact sport teams are facing major challenges to safely continue training and competition. We present the design and implementation of a structured monitoring concept for the Austrian national football league. 146 professional players from five clubs of the professional Austrian football league were monitored for a period of 12 weeks. Subjective health parameters, PCR- test results and data obtained from a geo-tracking app were collected. Simulations modelling the consequences of a COVID-19 case with increasing reproduction number were computed. No COVID -19 infection occurred during the observation period in the players. Infections in the nearer surroundings lead to increased perceived risk of infection. Geo tracking was particularly hindered due to technical problems and reluctance of users. Simulation models suggested a hypothetical shut-down of all training and competition activities. A structured monitoring concept can help to continue contact sports safely in times of a pandemic. Cooperation of all involved is essential.

Trial registration: ID: DRKS00022166 15/6/2020 https://www.who.int/ictrp/search/en/.
In vivo pair correlation microscopy reveals dengue virus capsid protein nucleocytoplasmic bidirectional movement in mammalian infected cells
Authors: Sallaberry Ignacio , Luszczak Alexis , Philipp Natalia , Navarro Guadalupe S. Costa , Gabriel Manuela V. , Gratton Enrico , Gamarnik Andrea V. , Estrada Laura C.
Published: December 2021

Flaviviruses are major human disease-causing pathogens, including dengue virus (DENV), Zika virus, yellow fever virus and others. DENV infects hundreds of millions of people per year around the world, causing a tremendous social and economic burden. DENV capsid (C) protein plays an essential role during genome encapsidation and viral particle formation. It has been previously shown that DENV C enters the nucleus in infected cells. However, whether DENV C protein exhibits nuclear export remains unclear. By spatially cross-correlating different regions of the cell, we investigated DENV C movement across the nuclear envelope during the infection cycle. We observed that transport takes place in both directions and with similar translocation times (in the ms time scale) suggesting a bidirectional movement of both C protein import and export.

Furthermore, from the pair cross-correlation functions in cytoplasmic or nuclear regions we found two populations of C molecules in each compartment with fast and slow mobilities. While in the cytoplasm the correlation times were in the 2–6 and 40–110 ms range for the fast and slow mobility populations respectively, in the cell nucleus they were 1–10 and 25–140 ms range, respectively. The fast mobility of DENV C in cytoplasmic and nuclear regions agreed with the diffusion coefficients from Brownian motion previously reported from correlation analysis. These studies provide the first evidence of DENV C shuttling from and to the nucleus in infected cells, opening new venues for antiviral interventions.
The association of apolipoproteins with later-life all-cause and cardiovascular mortality: a population-based study stratified by age
Authors: Ding Mozhu , Wennberg Alexandra , Ek Stina , Santoni Giola , Gigante Bruna , Walldius Göran , Hammar Niklas , Modig Karin
Published: December 2021

Midlife lipid levels are important predictors of cardiovascular diseases, yet their association with mortality in older adults is less clear. We aimed to (1) identify lipid profiles based on cholesterol, triglycerides, and apolipoproteins using cluster analysis, and (2) investigate how lipid profiles and lipid levels at different ages are associated with later-life all-cause and cardiovascular mortality. We used data from 98,270 individuals in the Swedish AMORIS cohort who had blood measurements between 1985–1996 and were followed until 2012. Over the follow-up (mean 18.0 years), 30,730 (31.3%) individuals died. Three lipid profiles were identified. Compared with reference profile, a high lipid profile (low ApoA-I and high total cholesterol (TC), triglycerides, ApoB, and ApoB/ApoA-I ratio) at ages 39–59 or 60–79 was associated with higher all-cause mortality. A high lipid profile at ≥ 80 years, however, did not confer higher mortality. For the specific markers, high TC (≥ 7.25 mmol/L) was associated with higher all-cause mortality in ages 39–59 but lower mortality in ages 60–79 and ≥ 80. Low ApoA-I (< 1.28 g/L) and high ApoB/ApoA-I ratio (≥ 1.18), on the other hand, were associated with higher cardiovascular mortality regardless of age at lipid measurement, highlighting their potential relevance for survival in both young and older individuals.
Enhanced catalysis through structurally modified hybrid 2-D boron nitride nanosheets comprising of complexed 2-hydroxy-4-methoxybenzophenone motif
Authors: Rana Pooja , Dixit Ranjana , Sharma Shivani , Dutta Sriparna , Yadav Sneha , Sharma Aditi , Kaushik Bhawna , Rana Pooja , Adholeya Alok , Sharma Rakesh K.
Published: December 2021

Tuning the structural architecture of the pristine two dimensional hexagonal boron nitride (h-BN) nanosheets through rational surface engineering have proven advantageous in the fabrication of competent catalytic materials. Inspired by the performance of h-BN based nanomaterials in expediting key organic transformations, we channelized our research efforts towards engineering the inherent surface properties of the exclusively stacked h-BN nanosheets through the incorporation of a novel competent copper complex of a bidentate chelating ligand 2-hydroxy-4-methoxybenzophenone (BP). Delightfully, this hybrid nanomaterial worked exceptionally well in boosting the [3 + 2] cycloaddition reaction of azide and nitriles, providing a facile access to a diverse variety of highly bioactive tetrazole motifs. A deep insight into the morphology of the covalently crafted h-BN signified the structural integrity of the exfoliated h-BN@OH nanosheets that exhibited lamellar like structures possessing smooth edges and flat surface. This interesting morphology could also be envisioned to augment the catalysis by allowing the desired surface area for the reactants and thus tailoring their activity. The work paves the way towards rational design of h-BN based nanomaterials and adjusting their catalytic potential by the use of suitable complexes for promoting sustainable catalysis, especially in view of the fact that till date only a very few h-BN nanosheets based catalysts have been devised.
Making nanostructured materials from maize, milk and malacostraca
Authors: Suriyanarayanan Subramanian , Nicholls Ian A.
Published: December 2021

Nano-structured materials are used in electronics, diagnostics, therapeutics, smart packaging, energy management and textiles, areas critical for society and quality of life. However, their fabrication often places high demands on limited natural resources. Accordingly, renewable sources for the feedstocks used in their production are highly desirable. We demonstrate the use of readily available biopolymers derived from maize (zein), milk (casein) and malacostraca (crab-shell derived chitin) in conjunction with sacrificial templates, self-assembled monodisperse latex beads and anodized aluminium membranes, for producing robust surfaces coated with highly regular hyperporous networks or wire-like morphological features, respectively. The utility of this facile strategy for nano-structuring of biopolymers was demonstrated in a surface based-sensing application, where biotin-selective binding sites were generated in the zein-based nano-structured hyperporous network.