bluuebunny/crossref_metadata_2025 huggingface dataset:
A parallel scalable domain decomposition preconditioner for elastic crack simulation using XFEM
Authors: Tian Wei , Huang Jingjing , Jiang Yi , Chen Rongliang
Published: March 2022

In this article, a parallel overlapping domain decomposition preconditioner is proposed to solve the linear system of equations arising from the extended finite element discretization of elastic crack problems. The algorithm partitions the computational mesh into two types of subdomains: the regular subdomains and the crack tip subdomains based on the observation that the crack tips have a significant impact on the convergence of the iterative method while the impact of the crack lines is not that different from those of regular mesh points. The tip subdomains consist of mesh points at crack tips and all neighboring points where the branch enrichment functions are applied. The regular subdomains consist of all other mesh points, including those on the crack lines. To overcome the mismatch between the number of subdomains and the number of processor cores, the proposed method is divided into two steps: solve the crack tip problem and then the regular subdomain problem during each iteration. The proposed method was used to develop a parallel XFEM package which is able to test different types of iterative methods. To achieve good parallel efficiency, additional methods were introduced to reduce communication and to maintain the load balance between processors. Numerical experiments indicate that the proposed method significantly reduces the number of iterations and the total computation time compared to the classical methods. In addition, the method scales up to 8192 processor cores with over 70% parallel efficiency to solve problems with more than degrees of freedom.
The effect of near‐surface azimuthal anisotropy on a joint interpretation of seismic and electrical resistivity data
Authors: Yaskevich Sergey V. , Dergach Petr A. , Chernyshov Gleb S. , Nevedrova Nina N. , Sanchaa Aidisa , Shalaginov Alexander E. , Duchkov Anton A. , Gorshkalev Sergey B. , Karsten Wladimir
Published: March 2022

In this paper, we study the anisotropic near surface with seismic refraction surveying and electrical resistivity tomography. We present a field data processing case study and show a significant dependence of the determined P‐ wave velocity and electrical resistivity on the acquisition line direction. We show that the anisotropy influences not only the determined velocities themselves, but also the estimated depths of the determined boundaries and can cause misinterpretation of the arrival time curves and lead to hidden layer issues. We justify our field data‐processing results with ray modelling and synthetic data processing. As a result of our case study, we suggest a consistent direction of anisotropy for electrical resistivity and seismic surveying for the particular site in the Novosibirsk region.
A DNA Biosensor Based on a Raspberry‐like Hierarchical Nano‐structure for the Determination of the Anticancer Drug Nilotinib
Authors: Moarefdoust Mohammad Mehdi , Jahani Shohreh , Moradalizadeh Mehran , Motaghi Mohammad Mehdi , Foroughi Mohammad Mehdi
Published: March 2022

It is crucial to design fast, sensitive and affordable deoxyribonucleic acid (DNA) recognition instruments, and elucidate changes in DNA structure, for studying the interaction between DNA and chemotherapy drugs. Therefore, a DNA biosensor, based on a carbon paste electrode (CPE), modified with raspberry‐like indium(III)/nickel oxide hierarchical nano‐structures (In3+/NiO RLHNSs) was constructed. An electrochemical readout should then give information on the interactions between anticancer drugs and double‐stranded (ds)‐DNA. The morphology as well as the electrochemical description of this new biosensor is described. Based on experimentally determined optimal conditions, ds‐DNA modified with In3+/NiO RLHNSs/CPE was used to evaluate the binding interaction of nilotinib, as an anti‐cancer drug, with DNA through differential pulse voltammetry (DPV), UV‐Vis spectroscopy, viscosity measurements and a computational docking process. The analyses indicated the linearity of the guanine oxidation signal at nilotinib concentration is given between 0.01 and 50.0 μm, with the limit of detection (LOD) equal to 0.62 nm. Additionally, the equilibrium constant (K) for the binding was determined to 1.5×104 m−1. Through the quantitative measurement of nilotinib in serum samples with a high recovery rate of 101.3–98.0 %, the applicability of this approach was demonstrated. As a whole, this DNA biosensor may be promising for various bio‐interactions.
Governing with health code: Standardising China's data network systems during COVID‐19
Authors: Sun Yu , Wang Wilfred Yang
Published: March 2022

Noting the infrastructural turn in platform studies, the article conceives China's health code system, Jian Kang Ma (JKM), deployed to manage the COVID‐19 crisis as a new social infrastructure that manifests the symbolic and material power of the Party State. Using the platform walkthrough method and documentary inquiry, we unpack the structures of platform governance and identify actors of the power to appreciate the socio‐political dynamics of platform algorithms. JKM's structural power is not monolithic in the name of the Party State but supports a process of structuration that operates across multiple actors, administrative bodies and, governing layers. JKM has centralised data systems through the building of a nationwide algorithmic standard of COVID‐19 governance. JKM typified the political dynamics of deterritorialisation, a reference to the state's governing mindset of eradicating local variants of policy implementation and governing autonomy in China. The removal of local power in pandemic administration has led to the production of a unified national subject. Such a comprehensive approach begs for greater nuance and sophisticated knowledge about those indigenous logics that platforms and algorithms operate and are embedded in, thus contributing to de‐westernising platform studies.
Spectroscopic, Structural and Energetic Properties of Pentanitroaniline
Authors: Klapötke Thomas M. , Krumm Burkhard , Riedelsheimer Christian
Published: March 2022

Although pentanitroaniline (PNA) has been known for almost 100 years, as well as with an optimized synthesis, it is still not fully characterized. In this contribution, the crystal structure of PNA is reported for the first time without any adducts or solvents, allowing a view of the crystal packing, as well as the exact positioning of the nitro groups relative to each other. In addition, based on the crystal structure, a Hirshfeld analysis was performed, which determines the distances and types of interactions of the outer atoms. The compound was also studied in detail by NMR, especially with respect to 13C and 14N, making this a challenge due to sensitivity in solution. Furthermore, the compound was fully characterized by IR spectroscopy and TGA, as well as the sensitivities, were measured. Using the density obtained from X‐ray crystallography, as well as the heat of formation calculated with the gaussian program package, the energetic parameters were calculated using explo5 computer code. The performance data were compared to the commonly used RDX and oxidizer ammonium perchlorate, as well as the structurally similar triaminotrinitro (TATB) and pentanitro (PNB) benzene.
A novel Phe‐206‐Leu mutation in acetolactate synthase confers resistance to penoxsulam in barnyardgrass (Echinochloa crus‐galli (L.) P. Beauv)
Authors: Fang Jiapeng , Yang Dongchen , Zhao Zerui , Chen Jinyi , Dong Liyao
Published: March 2022

BACKGROUND

Barnyardgrass (Echinochloa crus‐galli (L.) P. Beauv) has evolved resistance to the acetolactate synthase (ALS) inhibitor penoxsulam which is used to control weeds in rice fields in China. The present study is conducted to identify the target‐site resistance (TSR) mechanisms conferring resistance in a penoxsulam‐resistant population.

RESULTS

The ALS sensitivity in vitro of the resistant population was sixfold lower to penoxsulam than that of the sensitive population. ALS sequencing revealed that no known mutation conferring ALS herbicide resistance was detected. However, a novel mutation Phe‐206‐Leu was identified in the ALS gene. Additionally, ALS gene expression level of the resistant population was lower than that of the sensitive population. Therefore, the penoxsulam resistance was not due to the overexpression of ALS gene. Molecular docking revealed that this mutation may change the interaction of the penoxsulam‐ALS binding and weaken its mutual affinity by approximately 10%. Arabidopsis thaliana transformed with mutant ALS had fourfold greater resistance to penoxsulam and varied cross‐resistance to other ALS herbicides than those transformed with sensitive ALS. Mutant and sensitive ALS proteins expressed by the baculovirus system exhibited different in vitro penoxsulam sensitivity levels. Mutant ALS had eightfold lower sensitivity to penoxsulam than sensitive ALS.

CONCLUSION

This report provides clear evidence that the ALS mutation at position 206 (Phe‐206‐Leu) confers penoxsulam resistance in barnyardgrass. Phe‐206 was confirmed to be the ninth amino acid residue related to ALS herbicide resistance in weeds. © 2022 Society of Chemical Industry.
SCI: A Bayesian adaptive phase I/II dose‐finding design accounting for semi‐competing risks outcomes for immunotherapy trials
Authors: Zhang Yifei , Guo Beibei , Cao Sha , Zhang Chi , Zang Yong
Published: March 2022

An immunotherapy trial often uses the phase I/II design to identify the optimal biological dose, which monitors the efficacy and toxicity outcomes simultaneously in a single trial. The progression‐free survival rate is often used as the efficacy outcome in phase I/II immunotherapy trials. As a result, patients developing disease progression in phase I/II immunotherapy trials are generally seriously ill and are often treated off the trial for ethical consideration. Consequently, the happening of disease progression will terminate the toxicity event but not vice versa, so the issue of the semi‐competing risks arises. Moreover, this issue can become more intractable with the late‐onset outcomes, which happens when a relatively long follow‐up time is required to ascertain progression‐free survival. This paper proposes a novel Bayesian adaptive phase I/II design accounting for semi‐competing risks outcomes for immunotherapy trials, referred to as the dose‐finding design accounting for semi‐competing risks outcomes for immunotherapy trials (SCI) design. To tackle the issue of the semi‐competing risks in the presence of late‐onset outcomes, we re‐construct the likelihood function based on each patient's actual follow‐up time and develop a data augmentation method to efficiently draw posterior samples from a series of Beta‐binomial distributions. We propose a concise curve‐free dose‐finding algorithm to adaptively identify the optimal biological dose using accumulated data without making any parametric dose–response assumptions. Numerical studies show that the proposed SCI design yields good operating characteristics in dose selection, patient allocation, and trial duration.
Multi‐Center Magnon Excitations Open the Entire Brillouin Zone to Terahertz Magnetometry of Quantum Magnets
Authors: Biesner Tobias , Roh Seulki , Razpopov Aleksandar , Willwater Jannis , Süllow Stefan , Li Ying , Zoch Katharina M. , Medarde Marisa , Nuss Jürgen , Gorbunov Denis , Skourski Yurii , Pustogow Andrej , Brown Stuart E. , Krellner Cornelius , Valentí Roser , Puphal Pascal , Dressel Martin
Published: March 2022

Due to the small photon momentum, optical spectroscopy commonly probes magnetic excitations only at the center of the Brillouin zone; however, there are ways to override this restriction. In case of the distorted kagome quantum magnet Y‐kapellasite, Y3Cu9(OH)19Cl8, under scrutiny here, the spin (magnon) density of states (SDOS) can be accessed over the entire Brillouin zone through three‐center magnon excitations. This mechanism is aided by the three different magnetic sublattices and strong short‐range correlations in the distorted kagome lattice. The results of THz time‐domain experiments agree remarkably well with linear spin‐wave theory (LSWT). Relaxing the conventional zone‐center constraint of photons gives a new aspect to probe magnetism in matter.
Passage efficiency and behaviour of sea lampreys (Petromyzon marinus, Linnaeus 1758) at a large marine–freshwater barrier
Authors: Griffioen Arie Benjamin , van Keeken Olvin Alior , Hamer Alicia Lianne , Winter Hendrik Volken
Published: March 2022

Passage success of sea lampreys Petromyzon marinus and behaviour in the vicinity of man‐made structures such as marine–freshwater barriers are poorly understood. To mitigate these migratory problems, a better understanding of passage behaviour is needed. To investigate this, 25 sea lampreys were tagged with V7 VEMCO acoustic transmitters at a large marine‐freshwater barrier, consisting of ten sluice gates and a ship lock complex in the Netherlands. Overall passage success was assessed to be 16%, with four sea lampreys passing the sluice gates, while none passed the ship locks. Successful passage through the barrier occurred either at the beginning or at the end of a discharge period, when water level differences between sea and lake and thus water velocities were relatively low. Most sea lamprey showed exploratory searching behaviour but only for a short duration, before leaving the area again when unsuccessful. Low passage success and search duration were likely related to the unnatural infrequent occurrence of flow and only short lasting windows with suitable conditions for passage at the sluice gates. To mitigate the poor migration success of sea lampreys at the marine‐freshwater barrier with the current adapted sluice management, a fish passage facility with lower water velocities and longer or continuous passage opportunities is needed.
Learning progressions as a simplified model: Examining teachers' reported uses to inform classroom assessment practices
Authors: Alonzo Alicia C. , Wooten Michelle M. , Christensen Julie
Published: March 2022

As models of how students' thinking may change over time, learning progressions (LPs) have been considered as supports for teachers' classroom assessment practices. However, like all models, LPs provide simplified representations of complex phenomena. One key simplification is the characterization of student thinking using levels—that is, the twin assumptions that student thinking is both coherent and consistent. While useful for the design of standards and curricula, the LP level simplification may threaten the basic premise that LPs could be used to diagnose a student's level and then provide tailored instruction in response. At the same time, our work with teachers suggests that, even with their simplifications, LPs may be useful in the classroom. Thus, rather than abandoning LPs, we sought to understand their potential affordances by exploring how teachers learn from LPs (knowledge‐for‐practice) and contribute to deeper understanding of LP use (knowledge‐of‐practice) as they identify and enact uses of these tools. To do so, we engaged high school physics teachers in a 2‐year, LP‐based professional development program. Based on qualitative analyses of planning meetings and interviews with the teachers, we describe how teachers used LPs to support classroom assessment with varying reliance on the LP level simplification. Although teachers used LPs in ways that relied on the coherence and consistency assumptions of the LP level simplification, uses of LPs that did not require these assumptions were more prevalent both within and across teachers. This study's findings have implications for research, teacher professional development, and the design of LPs.
Understanding the impact of COVID‐19 pandemic on teleworkers' experiences of perceived threat and professional isolation: The moderating role of friendship
Authors: Hu Xinyu (Judy) , Subramony Mahesh
Published: March 2022

Drawing from conservation of resource theory and the social support resource theory, this study examines how the severity of an exogenous disruptive event – the COVID‐19 pandemic – in one's community influences teleworkers' well‐being outcomes indirectly through their perceptions of pandemic‐related threat and experience of professional isolation, as well as the buffering effect of friendship on these relationships. Utilizing time‐lagged data from participants of a two‐wave survey panel (N = 351) and objective data of COVID‐19 severity from counties around the United States, we found that perceived threat, but not professional isolation, mediated the negative effect of proportion of confirmed COVID‐19 cases in the community on teleworkers' well‐being outcomes. Further, consistent with our predictions, support from friends significantly weakened the negative effects of threat and professional isolation on well‐being. Key theoretical and practical implications of this study are discussed.
Intelligent Nanodelivery System‐Generated 1O2 Mediates Tumor Vessel Normalization by Activating Endothelial TRPV4‐eNOS Signaling
Authors: Zhang Shuaiqiang , Li Yuanhao , Li Zhuoyue , Wang Guangxue , Liao Ai , Wang Jingru , Li Hui , Guo Zefeng , Cheng Boyang , Zhang Xuan
Published: March 2022

Tumor microenvironment (TME)‐responsive intelligent photodynamic therapy (PDT) systems have attracted increasing interest in anticancer therapy, due to their potential to address significant and unsatisfactory therapeutic issues, such as limited tissue penetration, inevitable normal tissue damage, and excessive impaired vessels. Here, an H2O2‐triggered intelligent LCL/ZnO PDT nanodelivery system is elaborately designed. LCL/ZnO can selectively regulate tumor‐derived endothelial cells (TECs) and specifically kill tumor cells, by responding to different H2O2 gradients in TECs and tumor cells. The LCL/ZnO is able to normalize tumor vessels, thereby resulting in decreased metastases, and ameliorating the immunosuppressive TME. Further analysis demonstrates that singlet oxygen (1O2)‐activated transient receptor potential vanilloid‐4‐endothelial nitric oxide synthase signals generated in TECs by LCL/ZnO induce tumor vascular normalization, which is identified as a novel mechanism contributing to the increased ability of PDT to promote cancer therapy. In conclusion, designing an intelligent PDT nanodelivery system response to the TME, that includes both selective TECs regulation and specific tumor‐killing, will facilitate the development of effective interventions for future clinical applications.
Campanian (Late Cretaceous) Theonellidae and Phymaraphiniidae (lithistid Demospongiae) from the Miechów and Mogilno‐Łódź synclinoria (southern and central Poland): new data and taxonomic revision
Authors: Świerczewska‐Gładysz Ewa , Jurkowska Agata
Published: March 2022

Theonellid and phymaraphiniid sponges were described for the first time in assemblages of Campanian lithistid Demospongiae collected from Miocene gravels in the Bełchatów lignite mine (Mogilno‐Łódź Synclinorium, central Poland). Here we add an analysis of sponges from museum collections, as well as of newly collected material from Campanian strata in the Miechów Synclinorium. Four phymaraphiniid and 11 theonellid species have been distinguished in these assemblages. Two phymaraphiniid species (Phymaraphinia infundibuliformis and Prokaliapsis janus), and five theonellids (Rhagadinia doederleini, Rhoptrum scytaliforme, Astrocladia laevis, Colossolacis plicata and Phyllodermia antiqua) have not been recorded previously from the Campanian of Poland. With three exceptions, all other theonellids and phymaraphiniids described herein are also known from the Campanian of Subhercynian and/or Lower Saxony basins in Germany. On account of the good preservation of the sponge skeletons, new data on the choanosomal and ectosomal spicules of Cretaceous theonellids and phymaraphiniids can now be presented. Our analysis of the distribution of theonellids and phymaraphiniids in various Cretaceous facies has allowed palaeoenvironmental factors conducive to the settlement of these sponges to be outlined.
Experimental Study on the Mechanism of Pinching in Cold‐Rolling Processes
Authors: Cometa Antonella , Geijselaers Hubertus Josephus Maria , van den Boogaard Antonius Henricus , Wentink Derk Jan , Hol Camile Wilbert José , Jacobs Leonardus Joannes Matheus
Published: March 2022

Herein, an experimental investigation into the occurrence of “pinching” defects during cold‐rolling of thin metal sheets is presented. Pinched strips are typically characterized by repetitive ripples and local ruptures, which can cause strip breaks. Even though pinches are a widely experienced phenomenon in both hot‐ and cold‐rolling of steel strips, no previous studies are known that have investigated the underlying mechanism for pinching during continuous rolling processes. Therefore, a set of rolling experiments is performed in a single‐stand pilot mill to create pinches by applying sudden perturbations in the process conditions. For the rolling settings chosen in the performed experiments, it is found that disruptions in the lubrication state are a powerful approach to induce shape defects, which develop as pinches. Herein, a first extensive description of the pinching mechanism is provided, as observed during the trials, by monitoring the strip's behavior and analyzing the damaged sheets. It is shown that ripples in these pinched strips are the result of folds, which form in the roll bite. The folds originate from the waviness of the strip upstream of the bite, being created by nonuniform conditions over the width of the strip.
Rangewide Population Structure of the Clearnose Skate
Authors: Nelson Lindsey Noel , Jones Christian M. , McDowell Jan R.
Published: March 2022

Skates (family Rajidae) are benthic elasmobranchs that are highly vulnerable to incidental fishery bycatch, are discarded at sea, and are poorly accounted for in catch records. Many aspects of skate life history, such as population structure, are not well understood. Without this knowledge, indiscriminate removal may have deleterious effects on scientific, conservation, and management efforts. The Clearnose SkateRostroraja eglanteriais seasonally migratory and widely distributed in the coastal waters of the eastern United States and in the northeastern Gulf of Mexico. This study used molecular techniques to assess the population structure of Clearnose Skate for use as a biological reference point for further research and management. Specimens were collected from 2014 to 2019 by fisheries‐independent surveys. High‐throughput genotyping‐by‐sequencing was used to identify single nucleotide polymorphisms, resulting in two data sets: one consisting of 8,914 loci (outlier and neutral) and the other comprised of 30 outlier loci. Results from all analyses and using both data sets indicated a high level of genetic differentiation between specimens from the Gulf of Mexico and specimens from the U.S East Coast. Using the outlier data set, a low but significant level of genetic differentiation was also found among specimens from the U.S. East Coast, with a subtle break near the North Carolina and South Carolina border. Genetic differences along the U.S. East Coast were spatially autocorrelated, indicating a latitudinal genetic gradient. The level of observed genetic differentiation between the Gulf of Mexico and the U.S. East Coast is likely due to physical barriers such as Florida and the Gulf Stream current, while the subtle structure along the U.S. East Coast is likely attributable to isolation caused by dispersal limitations and local temperature preferences. The results from this investigation of Clearnose Skate population structure can be used to better monitor and manage this vulnerable elasmobranch.
Influence of coupling ratio on seismic behavior of hybrid coupled partially encased composite wall system
Authors: Zhou Qiaoling , Su Mingzhou , Shi Yun , Jiang Lu , Zhang Lili , Guan Lingyu , Yang Yukun
Published: March 2022

Partially encased composite (PEC) members are novel composite members that efficiently exploit the advantages of mechanical properties of concrete and steel. However, the application of PEC members is limited to low‐ and mid‐rise buildings. To overcome this limitation, a study was conducted to assess the seismic performance of a newly proposed steel–concrete hybrid coupled wall consisting of PEC wall piers coupled by means of steel beams. Parametric analysis was conducted to investigate the elastic coupling ratio (CRelastic) and the way of changing CRelastic on the seismic behavior of the hybrid coupled PEC wall. The results showed that the CRelastic was the main parameter that affected the seismic performance of the wall. The way of changing CRelastic had little influence on the trend of the energy dissipation capacity and strength reservation of the wall. The failure mode and the development of plastic hinges of the wall were also not affected by the way of changing CRelastic. Both too large and too small CRelastic were detrimental to the seismic performance of the wall. To form an ideal plastic hinge development mode and experience good seismic performance, it is suggested that the reasonable range of CRelastic for the wall was 60%–70%.
From topological amplitude to rescattering dynamics
Authors: Wang Di
Published: March 2022

Abstract

We proposed a theoretical framework to correlate the topological diagram at quark level and rescattering dynamics at hadron level. In the framework, both the hadronic triangle diagram, and the topological-scattering diagram, which is the intermediate structure between topological diagram and triangle diagram, are expressed in the tensor form. The completeness of topological-scattering diagram is confirmed by the quark substructure of meson-meson scattering. The coefficient of each triangle diagram can be derived from the topological-scattering diagram and the total rescattering amplitudes are consistent with the ones derived from the chiral Lagrangian. If only the short-distance T diagram is considered as the weak vertex in triangle diagram, the rescattering contributions in the C, E and P diagrams have definite proportional relation of L(C) : L(E) : L(P) = −2 : 1 : 1 under the SU (3)F symmetry, and the rescattering contributions in the T and A diagrams only arise from the SU (3)F breaking effects. Taking D → Kπ and D → ππ modes as examples, we present our framework in detail. We find the Isospin relations in these decays are still valid in terms of triangle diagrams. Besides, the conclusions in the D meson decays under the SU(3)F symmetry can be generalized to the B meson decays under the SU(4)F symmetry.
Mixing and CP violation in D0 → K−π+ decays
Authors: Pajero Tommaso , Morello Michael Joseph
Published: March 2022

Abstract

We review the experimental methods to measure mixing and time-dependent CP violation in D0 decays into two hadrons. While these phenomena are usually neglected for D0 → K−π+ decays, this approximation is not always justified. In particular, it produces a bias on the measurement of the parameter yCP, when this is performed by relying on D0 → K−π+ decays as a normalisation channel, whose size is around 40% of the precision of the current world average. Finally, we estimate the sensitivity to the weak mixing phases achievable by studying D0 → K−π+ and untagged D → K−π+ decays, where D stands for either of the D0 and $$ \overline{D} $$

D
¯

0 mesons. Contrary to Cabibbo-suppressed D0 → h+h− decays, these decay channels allow to measure these phases without final-state dependent nuisance contributions from the decay amplitudes, but their sensitivity is lower by a factor of six.
Characters, quasinormal modes, and Schwinger pairs in dS2 with flux
Authors: Grewal Manvir , Parmentier Klaas
Published: March 2022

Abstract

An integral representation of the 1-loop partition function for charged scalars and spinors, minimally coupled to a uniform U(1) field on S2, is given in terms of SO(1, 2) Harish-Chandra group characters and evaluated exactly in terms of Hurwitz ζ-functions. Analytically continuing the U(1) field, we interpret the path integrals as quasicanonical partition functions in dS2 with an electric field. The character itself is obtained as a trace over states living at the future boundary of de Sitter and has a quasinormal mode expansion. The imaginary part of the partition function captures Schwinger pair creation in the static patch at finite temperature. The thermal enhancement is most noticeable for scalar masses below Hubble and leads to non-monotonicity of the current as a function of the field. This parameter range, when dimensionally reducing from a charged or rotating Nariai spacetime, is excluded by Swampland-inspired bounds. Around the AdS2 black hole, in contrast to dS2, there is a threshold to pair creation.
Fibrotic activity quantified in serum by measurements of type III collagen pro-peptides can be used for prognosis across different solid tumor types
Authors: Willumsen Nicholas , Jensen Christina , Green George , Nissen Neel I. , Neely Jaclyn , Nelson David M. , Pedersen Rasmus S. , Frederiksen Peder , Chen Inna M. , Boisen Mogens K. , Johansen Astrid Z. , Madsen Daniel H. , Svane Inge Marie , Lipton Allan , Leitzel Kim , Ali Suhail M. , Erler Janine T. , Hurkmans Daan P. , Mathijssen Ron H. J. , Aerts Joachim , Eslam Mohammed , George Jacob , Christiansen Claus , Bissel Mina J. , Karsdal Morten A.
Published: March 2022

Due to activation of fibroblast into cancer-associated fibroblasts, there is often an increased deposition of extracellular matrix and fibrillar collagens, e.g. type III collagen, in the tumor microenvironment (TME) that leads to tumor fibrosis (desmoplasia). Tumor fibrosis is closely associated with treatment response and poor prognosis for patients with solid tumors. To assure that the best possible treatment option is provided for patients, there is medical need for identifying patients with high (or low) fibrotic activity in the TME. Measuring unique collagen fragments such as the pro-peptides released into the bloodstream during fibrillar collagen deposition in the TME can provide a non-invasive measure of the fibrotic activity. Based on data from 8 previously published cohorts, this review provides insight into the prognostic value of quantifying tumor fibrosis by measuring the pro-peptide of type III collagen in serum of a total of 1692 patients with different solid tumor types and discusses the importance of tumor fibrosis for understanding prognosis and for potentially guiding future drug development efforts that aim at overcoming the poor outcome associated with a fibrotic TME.
Opposing roles of the entero-pancreatic hormone urocortin-3 in glucose metabolism in rats
Authors: Grunddal Kaare V. , Trammell Samuel A. J. , Bæch-Laursen Cecilie , Andersen Daniel B. , Xu Stella F. S. , Andersen Helle , Gillum Matthew P. , Ghiasi Seyed M. , Novak Ivana , Tyrberg Björn , Li Chien , Rosenkilde Mette M. , Hartmann Bolette , Holst Jens J. , Kuhre Rune E.
Published: March 2022

Aim/hypothesis

Urocortin-3 (UCN3) is a glucoregulatory peptide produced in the gut and pancreatic islets. The aim of this study was to clarify the acute effects of UCN3 on glucose regulation following an oral glucose challenge and to investigate the mechanisms involved.

Methods

We studied the effect of UCN3 on blood glucose, gastric emptying, glucose absorption and secretion of gut and pancreatic hormones in male rats. To supplement these physiological studies, we mapped the expression of UCN3 and the UCN3-sensitive receptor, type 2 corticotropin-releasing factor receptor (CRHR2), by means of fluorescence in situ hybridisation and by gene expression analysis.

Results

In rats, s.c. administration of UCN3 strongly inhibited gastric emptying and glucose absorption after oral administration of glucose. Direct inhibition of gastrointestinal motility may be responsible because UCN3’s cognate receptor, CRHR2, was detected in gastric submucosal plexus and in interstitial cells of Cajal. Despite inhibited glucose absorption, post-challenge blood glucose levels matched those of rats given vehicle in the low-dose UCN3 group, because UCN3 concomitantly inhibited insulin secretion. Higher UCN3 doses did not further inhibit gastric emptying, but the insulin inhibition progressed resulting in elevated post-challenge glucose and lipolysis. Incretin hormones and somatostatin (SST) secretion from isolated perfused rat small intestine was unaffected by UCN3 infusion; however, UCN3 infusion stimulated secretion of somatostatin from delta cells in the isolated perfused rat pancreas which, unlike alpha cells and beta cells, expressed Crhr2. Conversely, acute antagonism of CRHR2 signalling increased insulin secretion by reducing SST signalling. Consistent with these observations, acute drug-induced inhibition of CRHR2 signalling improved glucose tolerance in rats to a similar degree as administration of glucagon-like peptide-1. UCN3 also powerfully inhibited glucagon secretion from isolated perfused rat pancreas (perfused with 3.5 mmol/l glucose) in a SST-dependent manner, suggesting that UCN3 may be involved in glucose-induced inhibition of glucagon secretion.

Conclusions/interpretation

Our combined data indicate that UCN3 is an important glucoregulatory hormone that acts through regulation of gastrointestinal and pancreatic functions.

Graphical abstract
Developmental Differences in Left Ventricular Strain in IUGR vs. Control Children the First Three Months of Life
Authors: Änghagen Olov , Engvall Jan , Gottvall Tomas , Nelson Nina , Nylander Eva , Bang Peter
Published: March 2022

Background

Intrauterine growth restriction (IUGR) may directly affect cardiovascular function in early life. Longitudinal data on left ventricular longitudinal strain (LVLS), a key measure of cardiac function independent of body size, is not available. We hypothesize impaired cardiac function among IUGR newborns and persistence of the impairment until age 3 months.

Method

This is a prospective cohort study of consecutive pregnancies where IUGR was identified at 18–38 weeks gestational age (GA) with healthy controls randomly selected at 18–20 weeks GA. Echocardiograms were performed at birth and at age 3–4 months, and then compared.

Results

At birth, mean (SD) LVLS did not differ between the IUGR group [N = 19; − 15.76 (3.12) %] and controls [N = 35; − 15.53 (3.56) %]. The IUGR group demonstrated no significant change in LVLS at age 3–4 months [− 17.80 (3.82) %], while the control group [− 20.91 (3.31) %] showed a significant increase (P < 0.001). Thus, LVLS was lower in the IUGR group at age 3–4 months (P = 0.003).

Conclusion

The lack of increase in LVLS may suggest that IUGR has a direct impact on cardiac function as early as during the first months of life.

Trial registration Clinical trials.gov Identifier: NCT02583763, registration October 22, 2015. Retrospectively registered September 2014–October 2015, thereafter, registered prospectively.
Shorter effective lifespan in laboratory populations of D. melanogaster might reduce sexual selection
Authors: Mital Avani , Sarangi Manaswini , Nandy Bodhisatta , Pandey Neha , Joshi Amitabh
Published: March 2022

The role of sexual selection in mediating levels of sexual conflict has been demonstrated in many experimental evolution studies on Drosophila spp. where competition among males for mating was the target of selection. Sexual selection has also been shown to affect the evolution of life-histories. However, the influence of divergent life-histories on reproductive strategies and, therefore, sexual selection and possibly sexual conflict has been less well studied. We examined D. melanogaster populations selected for a short development time and early age at reproduction for changes in reproductive behavior and traits that are proxies of sexual selection. We report a large reduction in reproductive competition experienced by the males of these populations, compared to ancestral populations that are not consciously selected for rapid development or early reproduction, potentially leading to reduced sexual selection. We show that rapidly developing and early reproducing populations have very low levels of mating in their lifetime (females are more or less monandrous), low courtship levels, shorter copulation duration, and longer time from eclosion to first mating, compared to the controls. These results are discussed in the context of the previously demonstrated reduction of inter-locus sexual conflict in these populations. We show that life-history strategies might have a large and significant impact on sexual selection, with each influencing the other and contributing to the complexities of adaptation.

Significance statement

Sexual conflict, often manifested as an arms-race between males and females trying to enhance their own reproductive success at some cost to the other, is of great evolutionary interest because it can maintain genetic variation in populations, prevent the independent optimization of male and female traits, and also promote speciation. Sexual selection, or variation in mating success, is well known to affect levels of sexual conflict. However, it is not so clear whether, and how, the regular evolution of life-histories also affects sexual selection. Here, we show that life-history evolution in fruit fly populations selected for traits not directly related to sexual conflict might, nevertheless, mediate the possible evolution of altered sexual conflict levels through effects on sexual selection. Populations that evolved to develop to adulthood fast, and reproduce relatively early in life, are shown to potentially experience less sexual selection, which can explain the low sexual conflict levels earlier observed in them.
Interobserver agreement and prognostic impact for MRI–based 2018 FIGO staging parameters in uterine cervical cancer
Authors: Wagner-Larsen Kari S. , Lura Njål , Salvesen Øyvind , Halle Mari Kyllesø , Forsse David , Trovik Jone , Smit Noeska , Krakstad Camilla , Haldorsen Ingfrid S.
Published: March 2022

Objectives

To evaluate the interobserver agreement for MRI–based 2018 International Federation of Gynecology and Obstetrics (FIGO) staging parameters in patients with cervical cancer and assess the prognostic value of these MRI parameters in relation to other clinicopathological markers.

Methods

This retrospective study included 416 women with histologically confirmed cervical cancer who underwent pretreatment pelvic MRI from May 2002 to December 2017. Three radiologists independently recorded MRI–derived staging parameters incorporated in the 2018 FIGO staging system. Kappa coefficients (κ) for interobserver agreement were calculated. The predictive and prognostic values of the MRI parameters were explored using ROC analyses and Kaplan–Meier with log-rank tests, and analyzed in relation to clinicopathological patient characteristics.

Results

Overall agreement was substantial for the staging parameters: tumor size > 2 cm (κ = 0.80), tumor size > 4 cm (κ = 0.76), tumor size categories (≤ 2 cm; > 2 and ≤ 4 cm; > 4 cm) (κ = 0.78), parametrial invasion (κ = 0.63), vaginal invasion (κ = 0.61), and enlarged lymph nodes (κ = 0.63). Higher MRI–derived tumor size category (≤ 2 cm; > 2 and ≤ 4 cm; > 4 cm) was associated with a stepwise reduction in survival (p ≤ 0.001 for all). Tumor size > 4 cm and parametrial invasion at MRI were associated with aggressive clinicopathological features, and the incorporation of these MRI–based staging parameters improved risk stratification when compared to corresponding clinical assessments alone.

Conclusion

The interobserver agreement for central MRI–derived 2018 FIGO staging parameters was substantial. MRI improved the identification of patients with aggressive clinicopathological features and poor survival, demonstrating the potential impact of MRI enabling better prognostication and treatment tailoring in cervical cancer.

Key Points

• The overall interobserver agreement was substantial (κ values 0.61–0.80) for central MRI staging parameters in the 2018 FIGO system.

• Higher MRI–derived tumor size category was linked to a stepwise reduction in survival (p ≤ 0.001 for all).

• MRI–derived tumor size > 4 cm and parametrial invasion were associated with aggressive clinicopathological features, and the incorporation of these MRI–derived staging parameters improved risk stratification when compared to clinical assessments alone.
Could detection and attribution of climate change trends be spurious regression?
Authors: Cummins Donald P. , Stephenson David B. , Stott Peter A.
Published: March 2022

Since the 1970s, scientists have developed statistical methods intended to formalize detection of changes in global climate and to attribute such changes to relevant causal factors, natural and anthropogenic. Detection and attribution (D&A) of climate change trends is commonly performed using a variant of Hasselmann’s “optimal fingerprinting” method, which involves a linear regression of historical climate observations on corresponding output from numerical climate models. However, it has long been known in the field of time series analysis that regressions of “non-stationary” or “trending” variables are, in general, statistically inconsistent and often spurious. When non-stationarity is caused by “integrated” processes, as is likely the case for climate variables, consistency of least-squares estimators depends on “cointegration” of regressors. This study has shown, using an idealized linear-response-model framework, that if standard assumptions hold then the optimal fingerprinting estimator is consistent, and hence robust against spurious regression. In the case of global mean surface temperature (GMST), parameterizing abstract linear response models in terms of energy balance provides this result with physical interpretability. Hypothesis tests conducted using observations of historical GMST and simulation output from 13 CMIP6 general circulation models produced no evidence that standard assumptions required for consistency were violated. It is therefore concluded that, at least in the case of GMST, detection and attribution of climate change trends is very likely not spurious regression. Furthermore, detection of significant cointegration between observations and model output indicates that the least-squares estimator is “superconsistent”, with better convergence properties than might previously have been assumed. Finally, a new method has been developed for quantifying D&A uncertainty, exploiting the notion of cointegration to eliminate the need for pre-industrial control simulations.
New FPT Algorithms for Finding the Temporal Hybridization Number for Sets of Phylogenetic Trees
Authors: Borst Sander , van Iersel Leo , Jones Mark , Kelk Steven
Published: March 2022

We study the problem of finding a temporal hybridization network containing at most k reticulations, for an input consisting of a set of phylogenetic trees. First, we introduce an FPT algorithm for the problem on an arbitrary set of m binary trees with n leaves each with a running time of $$O(5^k\cdot n\cdot m)$$

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. We also present the concept of temporal distance, which is a measure for how close a tree-child network is to being temporal. Then we introduce an algorithm for computing a tree-child network with temporal distance at most d and at most k reticulations in $$O((8k)^d5^ k\cdot k\cdot n\cdot m)$$

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time algorithm for computing a temporal hybridization network for a set of two nonbinary trees. We also provide an implementation of all algorithms and an experimental analysis on their performance.
Full-length MAVS, a mitochondrial antiviral-signaling protein, inhibits hepatitis E virus replication, requiring JAK-STAT signaling
Authors: Qu Changbo , Li Yang , Li Yunlong , Pan Yihang
Published: March 2022

Hepatitis E virus (HEV) infection is the leading cause of acute hepatitis worldwide. The mitochondrial antiviral signaling protein (MAVS)-mediated interferon (IFN) response plays a pivotal role in hepatic antiviral immunity. However, little is known about the effect of overexpression of MAVS on HEV infection. Full-length MAVS (FL-MAVS) is the main form of MAVS that increases the production of IFNs. Here, we studied the effect of FL-MAVS on HEV infection. We found that overexpression of FL-MAVS profoundly inhibited HEV replication. Furthermore, we showed that the anti-HEV effect of FL-MAVS is largely dependent on JAK-STAT signaling activation.
Estimation of groundwater recharge rates using soil-water isotope profiles: a case study of two contrasting dune types on Langeoog Island, Germany
Authors: Post V. E. A. , Zhou T. , Neukum C. , Koeniger P. , Houben G. J. , Lamparter A. , Šimůnek J.
Published: March 2022

The creation of artificial dunes for coastal protection may have important consequences for freshwater lenses in coastal aquifers. The objective of this study was to compare the recharge processes below such a young dune with scant vegetation to an older dune covered by grass and herbaceous vegetation. To this aim, soil and water samples were collected from the unsaturated zone at two sites on Langeoog Island in northern Germany, and the soil water was analysed for stable water isotopes and chloride. Recharge rates were calculated by using a new version of HYDRUS-1D, which was modified to simulate isotope fractionation during evaporation. Both the model outcomes and the data highlight the importance of fractionation, which is slightly more pronounced at the older, more vegetated dune. At the newly constructed dune, vegetation dieback seemingly reduces the importance of transpiration during summer. Recharge occurs year-round, albeit predominantly during the winter months. Calculated recharge rates are consistent with lysimeter measurements, but are significantly higher than previously reported rates based on groundwater age data, which is primarily attributed to the absence of dune shrub at the sites investigated here. More data are needed to establish the importance of soil-water repellency and overland flow. Based on the results, it is proposed that repeated isotope sampling can yield important insights into the dynamics of recharge processes, including their response to climate change.
Subtle Differences in Brain Architecture in Patients with Congenital Anosmia
Authors: Thaploo Divesh , Georgiopoulos Charalampos , Haehner Antje , Hummel Thomas
Published: March 2022

People suffering from congenital anosmia show normal brain architecture although they do not have functional sense of smell. Some studies in this regard point to the changes in secondary olfactory cortex, orbitofrontal cortex (OFC), in terms of gray matter volume increase. However, diffusion tensor imaging has not been explored so far. We included 13 congenital anosmia subjects together with 15 controls and looked into various diffusion parameters like FA. Increased FA in bilateral OFC confirms the earlier studies reporting increased gray matter thickness. However, it is quite difficult to interpret FA in terms of gray matter volume. Increased FA has been seen with recovery after traumatic brain injury. Such changes in OFC point to the plastic nature of the brain.