bluuebunny/crossref_metadata_2025 huggingface dataset:
FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA
Authors: Mandal Raju , Kohoutova Klara , Petrvalska Olivia , Horvath Matej , Srb Pavel , Veverka Vaclav , Obsilova Veronika , Obsil Tomas
Published: April 2022

Transcription factor p53 protects cells against tumorigenesis when subjected to various cellular stresses. Under these conditions, p53 interacts with transcription factor Forkhead box O (FOXO) 4, thereby inducing cellular senescence by upregulating the transcription of senescence‐associated protein p21. However, the structural details of this interaction remain unclear. Here, we characterize the interaction between p53 and FOXO4 by NMR, chemical cross‐linking, and analytical ultracentrifugation. Our results reveal that the interaction between p53 TAD and the FOXO4 Forkhead domain is essential for the overall stability of the p53:FOXO4 complex. Furthermore, contacts involving the N‐terminal segment of FOXO4, the C‐terminal negative regulatory domain of p53 and the DNA‐binding domains of both proteins stabilize the complex, whose formation blocks p53 binding to DNA but without affecting the DNA‐binding properties of FOXO4. Therefore, our structural findings may help to understand the intertwined functions of p53 and FOXO4 in cellular homeostasis, longevity, and stress response.
In vivo liquid–liquid phase separation protects amyloidogenic and aggregation‐prone peptides during overexpression in Escherichia coli
Authors: Gabryelczyk Bartosz , Alag Reema , Philips Margaret , Low Kimberly , Venkatraman Anandalakshmi , Kannaian Bhuvaneswari , Shi Xiangyan , Linder Markus , Pervushin Konstantin , Miserez Ali
Published: April 2022

Studying pathogenic effects of amyloids requires homogeneous amyloidogenic peptide samples. Recombinant production of these peptides is challenging due to their susceptibility to aggregation and chemical modifications. Thus, chemical synthesis is primarily used to produce amyloidogenic peptides suitable for high‐resolution structural studies. Here, we exploited the shielded environment of protein condensates formed via liquid–liquid phase separation (LLPS) as a protective mechanism against premature aggregation. We designed a fusion protein tag undergoing LLPS in Escherichia coli and linked it to highly amyloidogenic peptides, including β amyloids. We find that the fusion proteins form membraneless organelles during overexpression and remain fluidic‐like. We also developed a facile purification method of functional Aβ peptides free of chromatography steps. The strategy exploiting LLPS can be applied to other amyloidogenic, hydrophobic, and repetitive peptides that are otherwise difficult to produce.
Multivalent Angiomotin‐like 1 and Yes‐associated protein form a dynamic complex
Authors: Vogel Amber , Crawford Alexandra , Nyarko Afua
Published: April 2022

Multivalent complexes formed between the cancer‐promoting transcriptional co‐activator, Yes‐associated protein (YAP), and proteins containing short linear motifs of type PPxY modulate cell proliferation and are attractive therapeutic targets. However, challenges producing PPxY polypeptides containing the full binding domain has limited understanding of the assembly process. Here, we successfully produced a polypeptide containing the complete set of three PPxY binding sites of Angiomotin‐like 1 (AMOTL1), a scaffolding protein that regulates the nucleo‐cytoplasmic shuttling of YAP via WW‐PPxY interactions. Using an array of biophysical techniques including isothermal titration calorimetry, size‐exclusion chromatography coupled to multi‐angle light scattering, and solution nuclear magnetic resonance spectroscopy, we show that the AMOTL1 polypeptide is partially disordered, and binds the YAP WW domains to form an ensemble of complexes of varying stabilities. The binding process is initiated by the binding of one YAP WW domain to one AMOTL1 PPxY motif and is completed by transient interactions of the second YAP WW domain with a second AMOTL1 PPxY motif to form an equilibrating mixture composed of various species having two YAP sites bound to two conjugate AMOTL1 sites. We rationalize that the transient interactions fine‐tune the stability of the complex for rapid assembly and disassembly in response to changes in the local cellular environment.
Partitioning the Hill coefficient into contributions from ligand‐promoted conformational changes and subunit heterogeneity
Authors: Roy Mousam , Horovitz Amnon
Published: April 2022

Heterooligomers that undergo ligand‐promoted conformational changes are ubiquitous in nature and involved in many essential processes. Conformational switching often leads to positive cooperativity in ligand binding that is reflected in a Hill coefficient with a value greater than one. The subunits comprising heterooligomers can differ, however, in their affinity for the ligand. Such so‐called site heterogeneity results in apparent negative cooperativity that is reflected by a Hill coefficient with a value less than one. Consequently, positive cooperativity due to the ligand‐promoted allosteric switch can be masked, in cases of such heterooligomers, by apparent negative cooperativity owing to site heterogeneity. Here, we derived expressions for the Hill coefficient, in the case of a heterodimer, in which the contributions from the ligand‐promoted allosteric switch and site heterogeneity are separated. Using these equations and simulations for higher order oligomers, we show under which conditions site heterogeneity can significantly mask the extent of observed positive cooperativity.
AustralianBryobiamites (Trombidiformes: Tetranychidae) form a complex of cryptic taxa with unique climatic niches and insecticide responses
Authors: Umina Paul A , Weeks Andrew R , Maino James L , Hoffmann Ary A , Song Sue Vern , Thia Joshua , Severtson Dustin , Cheng Xuan , van Rooyen Anthony , Arthur Aston A
Published: April 2022

BACKGROUND

Bryobia(Koch) mites belong to the economically important spider mite family, the Tetranychidae, with >130 species described worldwide. Due to taxonomic difficulties and most species being asexual, species identification relies heavily on genetic markers. Multiple putativeBryobiamite species have been identified attacking pastures and grain crops in Australia. In this study, we collected 79 field populations ofBryobiamites and combined these with 134 populations that were collected previously. We characterised taxonomic variation of mites using 28S rDNA amplicon‐based DNA metabarcoding using next‐generation sequencing approaches and direct Sanger sequencing. We then undertook species distribution modelling of the main genetic lineages and examined the chemical responses of multiple field populations.

RESULTS

We identified 47 unique haplotypes across all mites sampled that grouped into four distinct genetic lineages. These lineages have different distributions, with three of the four putative lineages showing different climatic envelopes, as inferred from species distribution modelling.Bryobiamite populations also showed different responses to a widely used insecticide (the organophosphate, omethoate), but not to another chemical (the pyrethroid, bifenthrin) when examined using laboratory bioassays.

CONCLUSION

Our findings indicate that cryptic diversity is likely to complicate the formulation of management strategies forBryobiamites. Although focussed on Australia, this study demonstrates the challenges of studyingBryobiaand highlights the importance of further research into this complex group of mites across the world. © 2022 The Authors.Pest Management Sciencepublished by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Novel insecticidal 1,6‐dihydro‐6‐iminopyridazine derivatives as competitive antagonists of insect RDL GABA receptors
Authors: Liu Genyan , Zhou Congwei , Zhang Zhisong , Wang Chenchen , Luo Xiaogang , Ju Xiulian , Zhao Chunqing , Ozoe Yoshihisa
Published: April 2022

BACKGROUND

The ionotropic γ‐aminobutyric acid (GABA) receptor (iGABAR) is an important target for insecticides and parasiticides. Our previous studies showed that competitive antagonists (CAs) of insect iGABARs have the potential to be used for developing novel insecticides and that the structural modification of gabazine (a representative CA of mammalian iGABARs) could lead to the identification of novel CAs of insect iGABARs.

RESULTS

In the present study, a novel series of 1,3‐di‐ and 1,3,5‐trisubstituted 1,6‐dihydro‐6‐iminopyridazines (DIPs) was designed using a versatile strategy and synthesized using facile methods. Electrophysiological studies showed that several target DIPs (30 μM) exhibited excellent antagonistic activities against common cutworm and housefly iGABARs consisting of RDL subunits. The IC50 values of 3‐(4‐methoxyphenyl), 3‐(4‐trifluoromethoxyphenyl), 3‐(4‐biphenylylphenyl), 3‐(2‐naphthyl), 3‐(3,4‐methylenedioxyphenyl), and 3,5‐(4‐methoxyphenyl) analogs ranged from 2.2 to 24.8 μM. Additionally, several 1,3‐disubstituted DIPs, especially 3‐(4‐trifluoromethoxyphenyl) and 3‐(3,4‐methylenedioxyphenyl) analogs, exhibited moderate insecticidal activity against common cutworm larvae, with >60% mortality at a concentration of 100 mg kg−1. Molecular docking studies showed that the oxygen atom on the three‐substituted aromatic ring could form a hydrogen bond with Arg254, which may enhance the activity of these DIPs against housefly iGABARs.

CONCLUSION

This systematic study indicated that the presence of a carboxyl side chain shorter by one methylene than that of gabazine at the 1‐position of the pyridazine ring is effective for maintaining the stable binding of these DIPs in insect iGABARs. Our study provides important information for the design of novel insect iGABAR CAs. © 2022 Society of Chemical Industry.
Magnetic Properties of Tetragonal SmFe12−xMox Alloys in Bulk and Melt‐Spun Ribbons
Authors: Rodríguez-Crespo Bosco , Garcia-Franco Andrés , Rosero-Romo James Janderson , Echevarria-Bonet Cristina , Porro Jose Maria , Saiz Paula G. , Salazar Daniel
Published: April 2022

Currently, electric motors and generators use high‐energy permanent magnets based on RE2Fe14B phases (RE: rare earth) with high amounts of RE often including heavy‐RE metals (Dy, Tb), the most critical group of the raw materials. REFe12 alloys are seen as potential alternatives to RE2Fe14B because they contain a significantly lower amount of RE metals with similar or better values of remanent magnetization (MR) and high magnetocrystalline anisotropy, which can give rise to a large energy product (BH)max. Herein, the effect of heat treatments on the coercivity and magnetic properties on melt‐spun ribbons of SmFe12−xMox (x = 0.5, 1) alloys with wheel speeds of 15 and 35 m s−1 is studied. The maximum coercivity after heat treatments is obtained in as‐spun ribbons at a speed of 35 m s−1. For the x = 0.5 ribbons, μ0Hc increases from 0.06 to 0.36 T, while for the x = 1.0 ones μ0Hc is enhanced from 0.02 to 0.34 T. The highest values of saturation magnetization are obtained for the x = 0.5 ribbons (≈145 Am2 kg−1).
Sintering Aid‐Assisted Growth of 0.95(K0.5Na0.5)NbO3–0.05(Bi0.5Na0.5)(Zr0.85Sn0.15)O3 Single Crystals by the Solid‐State Crystal Growth Method and Their Characterization
Authors: Uwiragiye Eugenie , Pham Thuy Linh , Fisher John G. , Lee Jong Sook , Lee Byoung Wan , Ko Jae Hyeon , Kim Hwang Pill , Jo Wook
Published: April 2022

In this work, 0.95(K0.5Na0.5)NbO3–0.05(Bi0.5Na0.5)(Zr0.85Sn0.15)O3 (KNN–BNZS) lead‐free piezoelectric single crystals are grown by the solid‐state crystal growth (SSCG) method and their phase transitions and properties characterized. Addition of an appropriate amount of Li2CO3 and Bi2O3 sintering aids considerably promotes single‐crystal growth. Chemical composition of the single crystal is similar to the nominal composition with a slight deficiency in Na and K as evaluated by electron probe microanalysis (EPMA). X‐Ray diffraction (XRD), electrical property measurements, and temperature‐controlled Raman scattering reveal that the phase transition near room temperature is from a rhombohedral to an orthorhombic or tetragonal phase. Wide temperature range Raman scattering and dielectric properties consistently indicate transitions associated with the phase transformations or boundaries of a phase coexistence region and further details. Nontrivial frequency dependence of dielectric properties is successfully parameterized by capacitance relaxations described by Debye and Cole–Cole responses with special constant phase elements with fixed exponents of 0.5 (Warburg elements). High‐frequency dielectric constants and additional dielectric relaxations and dc relaxations are deconvoluted. The modeling parameters indicate the phase transition temperatures (or boundaries of the phase coexistence region) unambiguously. Polarization–electric field and bipolar strain–electric field hysteresis loops show that the single crystal is a classic lossy ferroelectric material.
Thick‐Film Carbon Electrode Deposited onto a Biodegradable Fibroin Substrate for Biosensing Applications
Authors: Molinnus Denise , Janus Kevin A. , Fang Anyelina C. , Drinic Aleksander , Achtsnicht Stefan , Köpf Marius , Keusgen Michael , Schöning Michael J.
Published: April 2022

This study addresses a proof‐of‐concept experiment with a biocompatible screen‐printed carbon electrode deposited onto a biocompatible and biodegradable substrate, which is made of fibroin, a protein derived from silk of the Bombyx mori silkworm. To demonstrate the sensor performance, the carbon electrode is functionalized as a glucose biosensor with the enzyme glucose oxidase and encapsulated with a silicone rubber to ensure biocompatibility of the contact wires. The carbon electrode is fabricated by means of thick‐film technology including a curing step to solidify the carbon paste. The influence of the curing temperature and curing time on the electrode morphology is analyzed via scanning electron microscopy. The electrochemical characterization of the glucose biosensor is performed by amperometric/voltammetric measurements of different glucose concentrations in phosphate buffer. Herein, systematic studies at applied potentials from 500 to 1200 mV to the carbon working electrode (vs the Ag/AgCl reference electrode) allow to determine the optimal working potential. Additionally, the influence of the curing parameters on the glucose sensitivity is examined over a time period of up to 361 days. The sensor shows a negligible cross‐sensitivity toward ascorbic acid, noradrenaline, and adrenaline. The developed biocompatible biosensor is highly promising for future in vivo and epidermal applications.
Phonon Interference in the 1D Array of Carbon Nanotubes
Authors: Smirnov Valeri V.
Published: April 2022

The dynamics of the 1D array of single‐walled carbon nanotubes (CNTs), which interact by van der Waals forces, is considered. The molecular dynamics simulation shows that both the mutual displacements of the nanotubes and the deformations of their walls occur in the low‐frequency oscillations domain. The composite model taking into account both types of the nanotubes’ motions is developed in the framework of the thin elastic shell theory. Such an approach allows us to reduce the problem to the dynamics of the linear lattice with contact interaction. The dispersion relations are represented analytically and the multichannel propagation that results in phonon interference (the acoustical analog of the Fano resonance) is observed in the presence of the array's irregularities. The latter can be formed with redundant nanotubes, which are placed over the array in the grooves between neighbor sites. The calculations of the transmittance have been performed by the transfer matrix method for several typical configurations.
Mg‐Facilitated Growth of Cubic Boron Nitride by Ion Beam‐Assisted Molecular Beam Epitaxy
Authors: Storm David F. , Maximenko Sergey I. , Lang Andrew C. , Nepal Neeraj , Feygelson Tatyana I. , Pate Bradford B. , Affouda Chaffra A. , Meyer David J.
Published: April 2022

Trace amounts of Mg deposited on a diamond (100) substrate surface facilitate the growth of cubic boron nitride (c‐BN) by ion beam‐assisted molecular beam epitaxy. Fourier transform infrared spectroscopy indicates that films grown with Mg are cubic, while those without Mg are either hexagonal BN or lacking measurable cubic or hexagonal signatures. Initiating the growth with 0.005 monolayer equivalent of Mg is sufficient to yield epitaxial films with >99% c‐BN. Reflection high energy electron diffraction, electron energy loss spectroscopy, and X‐Ray photoelectron spectroscopy indicate the surface of the film to be sp2‐bonded BN, consistent with the results of other groups. High‐resolution scanning transmission electron microscopy reveals c‐BN with a high density of stacking faults and twinning. A model is proposed by which Mg locally diminishes the energy barrier to dissociation of the as‐deposited sp2‐bonded BN, facilitating the nucleation of c‐BN.
Preventive replacement policy of a system considering multiple maintenance actions upon a failure
Authors: Jiang Liying , Li Bo , Hu Jiawen
Published: April 2022

Age‐based preventive replacement policy has been extensively studied in the literature. Upon an unexpected failure, most studies assume that only one type of maintenance actions can be executed to restore the system back to work. For example, minimal repair or corrective replacement that bring the system to respective as‐bad‐as‐old and as‐good‐as‐new states. Few studies consider both two types of maintenance actions, while predetermine the structure of the maintenance policy. Modern systems are becoming increasingly complex. Besides minimal repair and corrective replacement, imperfect repair can also be carried out to restore a failed system back to work, which brings it to a state between as‐bad‐as‐old and as‐good‐as‐new. This study investigates an optimal age‐based replacement policy, where minimal repair, corrective replacement, and imperfect repair can be carried out upon an unexpected failure with different maintenance effects. We formulate the problem as a semi‐Markov decision process (SMDP), and prove the existence of the stationary optimal policy. The optimal preventive replacement age threshold and the corresponding optimal maintenance action upon each failure are jointly obtained to minimize the long‐term average maintenance cost per time unit. A numerical study is provided to illustrate the effectiveness of our proposed model.
On the confidence intervals of process capability index Cpm based on a progressive type‐II censored sample
Authors: Akdoğan Yunus
Published: April 2022

This paper is concerned with the process capability index in the case of the progressively type‐II censored sample. In particular, the asymptotic distribution of maximum likelihood estimators of the process capability index is derived and it is used to construct the approximate confidence intervals with the delta rule. In addition, five parametric bootstrap confidence intervals for the index are discussed, in contrast to approximate confidence intervals, do not require second derivatives of the likelihood function. A Monte Carlo simulation study is performed to observe the coverage probabilities and the average width of these intervals. Simulation results indicate that the approximate confidence interval is better than the bootstrap based confidence intervals in terms of the coverage probabilities. Two practical examples are presented to illustrate the usability of the method discussed here.
Structural and electronic properties of HfO2 films on Si through H2O2 wet oxidation with improved thermal stability
Authors: Yu Tung‐Yuan , Lin Kun‐Lin , Chen Pin‐Guang , Chou Tung‐Huan
Published: April 2022

The thermal stability and material properties of HfO2 thin films on Si substrates with and without H2O2 wet chemical oxidation were investigated. The HfO2 samples were deposited through plasma‐enhanced atomic layer deposition and subjected to thermal annealing. They were then examined using X‐ray diffraction, transmission electron microscopy, X‐ray photoelectron spectroscopy, reflection electron energy loss spectroscopy, and conductive atomic force microscopy. For the Si substrate without H2O2 wet chemical oxidation, a native oxide (~1.8 nm) was formed on the substrate before HfO2 deposition. After the annealing process at 600°C, the band gap (Eg) of the HfO2 films increased from 6.0 to 6.2 eV due to the diffusion of Si into HfO2. Furthermore, the conduction and valence band offsets (ΔEc and ΔEv, respectively) between HfO2 and Si changed from 1.02 to 1.42 and 3.86 to 3.66 eV, respectively. After the H2O2 wet oxidation of the Si substrate, a 1.5‐nm chemical oxide was formed instead of a native oxide. The band offset and Eg values of HfO2 were similar before and after 600°C annealing (ΔEv = 3.86 eV, ΔEc = 1.02 eV, and Eg = 6.0 eV), implying the high thermal stability of the HfO2 films. Accordingly, wet oxidation not only prevents diffusion from chemical oxide but also markedly improves the oxide leakage current, which is useful for developing highly efficient and thermally stable HfO2 gate oxides in Si‐based integrated circuit devices.
How large should the next study be? Predictive power and sample size requirements for replication studies
Authors: van Zwet Erik W. , Goodman Steven N.
Published: April 2022

We use information derived from over 40K trials in the Cochrane Collaboration database of systematic reviews (CDSR) to compute the replication probability, or predictive power of an experiment given its observed (two‐sided) ‐value. We find that an exact replication of a marginally significant result with has less than 30% chance of again reaching significance. Moreover, the replication of a result with still has only 50% chance of significance. We also compute the probability that the direction (sign) of the estimated effect is correct, which is closely related to the type S error of Gelman and Tuerlinckx. We find that if an estimated effect has , there is a 93% probability that its sign is correct. If , then that probability is 99%. Finally, we compute the required sample size for a replication study to achieve some specified power conditional on the ‐value of the original study. We find that the replication of a result with requires a sample size more than 16 times larger than the original study to achieve 80% power, while requires at least 3.5 times larger sample size. These findings confirm that failure to replicate the statistical significance of a trial does not necessarily indicate that the original result was a fluke.
Microfluidic Nanoparticles for Drug Delivery
Authors: Liu Yun , Yang Guangze , Hui Yue , Ranaweera Supun , Zhao Chun‐Xia
Published: April 2022

Nanoparticles (NPs) have attracted tremendous interest in drug delivery in the past decades. Microfluidics offers a promising strategy for making NPs for drug delivery due to its capability in precisely controlling NP properties. The recent success of mRNA vaccines using microfluidics represents a big milestone for microfluidic NPs for pharmaceutical applications, and its rapid scaling up demonstrates the feasibility of using microfluidics for industrial‐scale manufacturing. This article provides a critical review of recent progress in microfluidic NPs for drug delivery. First, the synthesis of organic NPs using microfluidics focusing on typical microfluidic methods and their applications in making popular and clinically relevant NPs, such as liposomes, lipid NPs, and polymer NPs, as well as their synthesis mechanisms are summarized. Then, the microfluidic synthesis of several representative inorganic NPs (e.g., silica, metal, metal oxide, and quantum dots), and hybrid NPs is discussed. Lastly, the applications of microfluidic NPs for various drug delivery applications are presented.
Laser Power Converter Architectures Based on 3C‐SiC with Efficiencies >80%
Authors: Lozano Javier F. , Seoane Natalia , Comesaña Enrique , Almonacid Florencia , Fernández Eduardo F. , García-Loureiro Antonio
Published: April 2022

High power laser transmission technology is based on energy transfer through a monochromatic laser onto a photovoltaic receiver avoiding the limitations of conventional wiring. Current technology, headed by GaAs‐based devices, faces two limitations: the intrinsic entropic losses and the degradation at high input power densities due to ohmic losses. Two novel laser power converters focused on overcoming these limitations are proposed. 3C‐SiC is used as base material because of its high bandgap (2.36 eV) and its excellent crystallographic properties in order to reduce the entropic losses. Also, the current decreases due to the inherent flux reduction of high energy photons. To minimize ohmic losses, a recently proposed vertical architecture is explored, which can significantly reduce series resistance around two orders of magnitude (≈10−5 Ω cm2). Furthermore, 3C‐SiC is also implemented in a conventional horizontal architecture to show the advantage of increasing the energy gap to reduce the ohmic losses. The two laser power converters obtain efficiencies above the state‐of‐the‐art (87.4% at 3000 W cm−2 for the vertical architecture and 81.1% at 100 W cm−2 for the horizontal architecture) Taking this into account, the new devices open a new route for ultrahigh efficiency remote powered systems.
“New Normal” implications for global talent in the wake of economic nationalism and slowdown
Authors: Showkat Saloome , Wani Tahir , Kaur Jaspreet
Published: April 2022

As a result of global economies' protectionist policies, followed by economic nationalism and a downturn, there is a shortage of talent with the requisite skills, knowledge, and abilities to meet the contingencies amid COVID‐19. The recent developments have necessitated multinational businesses to manage their talent in a new international business context. Therefore, the purpose of this paper is to explore the implications of the “New Normal” for global talent which is manifested by economic nationalism and slowdown. This study used an inductive method to qualitative research, conducted in‐depth interviews with 28 top executives from multinational corporations. The implications for the global talent emerged from the current study as skill enhancement based on the emerged business model; training and development pertinent to new responsibilities and activities; adaptability to changes in the macroenvironment; emphasis on employee proactivity, experimentation, and risk‐taking; emphasis on hyperspecialization to take on contract positions; global talent needs to participate in remote learning; global talent must emphasize on mental health issues; and registering in talent exchange programs to fill talent skill shortages.
Reimagining Discourse in the Classroom
Authors: Grifenhagen Jill F. , Barnes Erica M.
Published: April 2022

Classroom discourse serves an important role in language, literacy, and other content area learning in early childhood and elementary classrooms. In this article, the authors define discourse as it relates to teaching and learning and overview the background of research on the topic. Then classroom discourse is reconsidered in the current context, including the field's growing understanding of the importance of knowledge for literacy, increasingly diverse student populations, and the rising prevalence of technology for instruction. Two traditional classroom discourse practices, sharing time and small‐group discussions, are revisited with these considerations. Suggestions are presented for how educators may update their approach to facilitating these types of discourse activities.
Anaesthesia management of transvenous implantation of a single‐chamber, rate‐adaptive pacemaker in a donkey with high‐grade second and third degree atrioventricular block
Authors: d'Anselme Olivia , Robel Matthias , Schwarzwald Colin , Ringer Simone Katja
Published: April 2022

A 17‐year‐old, domestic, entire, male, miniature donkey with a history of syncope because of sinus bradycardia, high‐grade second degree and occasional third degree atrioventricular block was referred for pacemaker implantation under general anaesthesia. After local anaesthesia with topical EMLA cream and subcutaneous mepivacaine infiltration and following tranquilisation with intravenous acepromazine, a temporary pacing catheter was inserted via introducer catheter through the left jugular vein into the right ventricle's apex. After initiation of internal pacing, medetomidine and butorphanol were administered intravenously, followed by ketamine and diazepam. Maintenance of anaesthesia was with isoflurane combined with medetomidine and lidocaine constant‐rate infusions. Intramuscular morphine and intravenous medetomidine were administered for recovery. The procedure was uneventful with no anaesthesia‐related complications, and manually assisted recovery was smooth. The present report describes the anaesthetic challenges and management of pacemaker implantation under general anaesthesia in a miniature donkey.
Universal water service delivery: Insights on what it takes from Ghana
Authors: Kumasi Tyhra C. , Nyarko Kwabena B. , Antwi‐Agyei Philip
Published: April 2022

Attainment of the government of Ghana's ambitious target of providing safe and reliable basic water services to all persons in Ghana by 2025 requires urgent need to unravel localized barriers to achieve universal access and sustain it. Using the Life Cycle Cost Approach, this paper provides a framework in policy planning and estimates the quantum of funds that needs to be injected into construction, operation, and maintenance of water facilities in order to achieve full water coverage in a district. Using participatory approaches, data were collected from Bongo, East Gonja, and Wa districts of Ghana. Data collection was facilitated by Community Water and Sanitation Agency employing the Resources, Infrastructure, Demand, and Access Strategic Planning Tool. Results show that the total cost of achieving full coverage is estimated at US$ 10,342,190, US$ 15,828,421, and US$ 10,111,616 for Bongo, East Gonja, and Wa East, respectively, in the implementation of water coverage and sustainability activities spanning 2017–2025. We suggest that sustainable water services for all requires more than capital inflows. Strong leadership commitment, bolstered institutions, improved monitoring, and evaluation as well as adequate human resources are critical to ensuring that capital investments translate into effective service delivery.
Correction to: Period Estimation and Rhythm Detection in Timeseries Data Using BioDare2, the Free, Online, Community Resource
Authors: Zieliński Tomasz , Hay Johnny , Millar Andrew J.
Published: April 2022

The original version of the chapter “Period Estimation and Rhythm Detection in Timeseries Data Using BioDare2, the Free, Online, Community Resource” was previously published non-open access. This has now been changed to open access under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), and the copyright holder updated to “The Author(s)”. For further details, see license information in the chapter. The chapter and the book have been updated with the change.
Correction to: Characteristics of Adaptable Control of Production Systems and the Role of Self-organization Towards Smart Manufacturing
Authors: Estrada-Jimenez Luis Alberto , Nikghadam-Hojjati Sanaz , Barata Jose
Published: April 2022

Chapter “Characteristics of Adaptable Control of Production Systems and the Role of Self-organization Towards Smart Manufacturing” was previously published non-open access. It has now been changed to open access under a CC BY 4.0 license and the copyright holder updated to ‘The Author(s)’. The book has also been updated with this change.
Charged lepton flavor violation associated with heavy quark production in deep inelastic lepton-nucleon scattering via scalar exchange
Authors: Kiyo Yuichiro , Takeuchi Michihisa , Uesaka Yuichi , Yamanaka Masato
Published: April 2022

Abstract

We study charged lepton flavor violation (CLFV) associated with heavy quark pair production in lepton-nucleon deep-inelastic scattering ℓiN → ℓjq$$ \overline{q} $$

q
¯

X. Here ℓi and ℓj denote the initial and final leptons; N and X are respectively the initial nucleon and arbitrary final hadronic system. We employ a model Lagrangian in which a scalar and pseudoscalar mediator generates the CLFV. We derive heavy quark structure functions for scalar and pseudoscalar currents and compute momentum distributions of the final lepton for the process. Our focus is on the heavy quark mass effects in the final lepton momentum distribution. We clarify the necessity of inclusion of the heavy quark mass to obtain reliable theory predictions for the CLFV signal searches in the deep-inelastic scattering.
Searching for light new physics at the LHC via lepton-number violation
Authors: Bensalem Wafia , London David , Stolarski Daniel , Tonero Alberto
Published: April 2022

Abstract

We study the collider phenomenology of a simplified model containing a right-handed W in which the WR couples predominantly to the third generation in the quark sector. The model also includes a light Majorana neutrino, with M1 ∼ $$ \mathcal{O}(100) $$
O

100

GeV, giving rise to lepton-number-violating signatures that are visible at the LHC. Taking into account all the searches from the LHC and Tevatron, we find that this WR can still be as light as MR ∼ 300 GeV. We show that this type of new physics, and others like it, can be detected at the LHC using final states with three same-sign same-flavour leptons.
Euclidean time approach to entanglement entropy on lattices and fuzzy spaces
Authors: Allouche A. , Dou D.
Published: April 2022

Abstract

In a recent letter, Phys. Lett. B792 (2019) 60, we developed a novel Euclidean time approach to compute Rényi entanglement entropy on lattices and fuzzy spaces based on Green’s function. The present work is devoted in part to the explicit proof of the Green’s matrix function formula which was quoted and used in the previous letter, and on the other part to some applications of this formalism. We focus on scalar theory on 1+1 lattice. We also use the developed approach to systematically go beyond the Gaussian case by considering interacting models, in particular our results confirm earlier expectations concerning the correction to the entanglement at first order. We finally outline how this approach can be used to compute the entanglement entropy on fuzzy spaces for free and interacting scalar theories.
Saponin-based adjuvant-induced dendritic cell cross-presentation is dependent on PERK activation
Authors: Huis in ’t Veld Lisa G. M. , Ho Nataschja I. , Wassink Melisssa , den Brok Martijn H. , Adema Gosse J.
Published: April 2022

Saponin-based adjuvants (SBAs) are promising new adjuvants that stand out as they not only enforce CD4 + T cell-mediated immunity and antibody responses, but also induce an unprecedented level of antigen cross-presentation by dendritic cells (DC) and subsequent CD8 + T cell activation. We discovered that SBA’s ability to boost cross-presentation depends on the induction of lipid bodies (LBs). Moreover, the MHCIIloCD11bhiDC subset was identified to be most responsive to SBA-induced cross-presentation. The aim is to further unravel the mechanisms behind the induction of DC cross-presentation by SBAs. Here we show that SBAs specifically induce the PKR-like Endoplasmic Reticulum kinase (PERK) pathway and that SBA-induced DC cross-presentation is dependent on activation of the PERK pathway. PERK activation and LB formation are both crucial for SBA-induced cross-presentation and PERK inhibition has little or no effect on SBA-induced LB formation. SBA’s responsiveness, LB formation and PERK activation are specific for the MHCIIloCD11bhiDCs. These findings contribute to understanding the pathways involved in SBA-induced cross-presentation and immune activation which will ultimately lead to the development of vaccines with improved efficiency and safety.
The effect of the Rht1 haplotype on Fusarium head blight resistance in relation to type and level of background resistance and in combination with Fhb1 and Qfhs.ifa-5A
Authors: Buerstmayr Maria , Buerstmayr Hermann
Published: April 2022

Key message

The effect of the Rht1-genes on FHB resistance depends on anther extrusion and level of background resistance. Qfhs.ifa-5A increases resistance and anther extrusion as efficiently as semi-dwarfing alleles decrease it.

The semi-dwarfing reduced height alleles Rht-D1b and Rht-B1b have been deployed in modern wheat cultivars throughout the world, but they increase susceptibility to Fusarium head blight (FHB). Here, we investigated the impact of the Rht1 genes on anther retention (AR) in relation to FHB resistance using four different sets of near-isogenic lines (NILs) with contrasting levels and types of background FHB resistance. NILs were evaluated for FHB severity, plant height and AR in three greenhouse and three field trials using artificial spray inoculation. Rht-B1b and Rht-D1b alleles increased AR and FHB susceptibility in all genetic backgrounds. The magnitude of the effects differed between NIL groups. Increased FHB susceptibility largely followed increased AR. Differences in FHB susceptibility between tall and dwarf haplotypes were largest in the NIL group with the highest changes in AR. In the most resistant NIL group, dwarfed lines had only slightly higher AR than tall lines and maintained good resistance, while both tall and dwarf lines had high levels of retained anthers in the most susceptible NIL group. We further investigated the effect of the major Fusarium resistance QTL Fhb1 and Qfhs.ifa-5A in combination with the Rht1 genes. Qfhs.ifa-5A enhanced anther extrusion in tall as well as semi-dwarf haplotypes, whereas Fhb1 did not affect AR. Qfhs.ifa-5A supported FHB resistance more efficiently than Fhb1 in lines that were more responsive to AR, while both Fhb1 and Qfhs.ifa-5A were equally efficient in NILs that had high background resistance and low response to AR.
Endoscopically assisted reconstruction of chronic Achilles tendon ruptures and re-ruptures using a semitendinosus autograft is a viable alternative to pre-existing techniques
Authors: Nilsson Niklas , Gunnarsson Baldvin , Carmont Michael R. , Brorsson Annelie , Karlsson Jón , Nilsson Helander Katarina
Published: April 2022

Purpose

Achilles tendon ruptures are termed chronic after a delay in treatment for more than 4 weeks. The literature advocates surgical treatment with reconstruction to regain ankle push-off strength. The preferred technique is, however, still unknown and is often individualized. This study aims to present the technique and clinical outcome of an endoscopically assisted free semitendinosus reconstruction of chronic Achilles tendon rupture and Achilles tendon re-ruptures with delayed representation. It is hypothesized that the presented technique is a viable and safe alternative for distal Achilles tendon ruptures and ruptures with large tendon gaps.

Method

Twenty-two patients (13 males and 9 females) with a median (range) age of 64 (34–73) treated surgically with endoscopically assisted Achilles tendon reconstruction using a semitendinosus autograft were included. The patients were evaluated at 12 months post-operatively for Achilles tendon Total Rupture Score (ATRS), calf circumference, Achilles Tendon Resting Angle (ATRA), heel-rise height and repetitions together with tendon length determined by ultrasonography, concentric heel-rise power and heel-rise work.

Results

The patients reported a median (range) ATRS of 76 (45–99) out of 100. The median (range) ATRA on the injured side was 60° (49°-75°) compared with 49.5° (40–61°), p < 0.001, on the non-injured side. Eighteen out of 22 patients were able to perform a single-leg heel-rise on the non-injured side. Sixteen patients out of those 18 (89%) were also able to perform a single heel-rise on the injured side. They did, however, perform significantly lower number of repetitions compared with the non-injured side with a median (range) heel-rise repetitions of 11 (2–22) compared with 26 (2–27), (p < 0.001), and a median (range) heel-rise height of 5.5 cm (1.0–11.0 cm) compared with 9.0 cm (5.0–11.5 cm), (p < 0.001). The median calf circumference was 1.5 cm smaller on the injured side, 37.5 cm compared with 39 cm, when medians were compared. The median (range) tendon length of the injured side was 24.8 cm (20–28.2 cm) compared with 22 cm (18.4–24.2 cm), (p < 0.001), on the non-injured side.

Conclusion

The study shows that endoscopically assisted reconstruction using a semitendinosus graft to treat chronic Achilles tendon ruptures and re-ruptures with delayed representation produces a satisfactory outcome. The technique can restore heel-rise height in patients with more distal ruptures or large tendon defects and is therefore a viable technique for Achilles tendon reconstruction.

Level of evidence

IV.
Entropy and convergence analysis for two finite volume schemes for a Nernst–Planck–Poisson system with ion volume constraints
Authors: Gaudeul Benoît , Fuhrmann Jürgen
Published: April 2022

In this paper, we consider a drift-diffusion system with cross-coupling through the chemical potentials comprising a model for the motion of finite size ions in liquid electrolytes. The drift term is due to the self-consistent electric field maintained by the ions and described by a Poisson equation. We design two finite volume schemes based on different formulations of the fluxes. We also provide a stability analysis of these schemes and an existence result for the corresponding discrete solutions. A convergence proof is proposed for non-degenerate solutions. Numerical experiments show the behavior of these schemes.
Pulse Wave Velocity Measurements by Magnetic Resonance Imaging in Neonates and Adolescents: Methodological Aspects and Their Clinical Implications
Authors: Lundström Simon , Liefke Jonas , Heiberg Einar , Hedström Erik
Published: April 2022

Pulse wave velocity (PWV) by cardiovascular magnetic resonance (CMR) lacks standardization. The aim of this study was to investigate methodological aspects of PWV measurements by CMR in neonates and adolescents. A computer phantom was created to validate the temporal resolution required for accurate PWV. Fifteen neonates and 71 adolescents underwent CMR with reference standard 3D angiography and phase-contrast flow acquisitions, and in a subset coronal overview images. Velocity and flow curves, transit time methods (time-to-foot (TTF), maximum upslope, and time-to-peak (TTP)), and baseline correction methods (no correction, automatic and manual) were investigated. In neonates, required timeframes per cardiac cycle for accurate PWV was 42 for the aortic arch and 41 for the thoracic aorta. In adolescents, corresponding values were 39 and 32. Aortic length differences by overview images and 3D angiography in adolescents were − 16–18 mm (aortic arch) and − 25–30 mm (thoracic aorta). Agreement in PWV between automatic and manual baseline correction was − 0.2 ± 0.3 m/s in neonates and 0.0 ± 0.1 m/s in adolescents. Velocity and flow-derived PWV measurements did not differ in either group (all p > 0.08). In neonates, transit time methods did not differ (all p > 0.19) but in adolescents PWV was higher for TTF (3.8 ± 0.5 m/s) and maximum upslope (3.7 ± 0.6 m/s) compared to TTP (2.7 ± 1.0 m/s; p < 0.0001). This study is a step toward standardization of PWV in neonates and adolescents using CMR. It provides required temporal resolution for phase-contrast flow acquisitions for typical heartrates in neonates and adolescents, and supports 3D angiography and time-to-foot with automatic baseline correction for accurate PWV measurements.
The (extended) achondroplasia foramen magnum score has good observer reliability
Authors: Jenko Nathan , Connolly Daniel J. A. , Raghavan Ashok , Fernandes James A. , Ushewokunze Shungu , Elphick Heather E. , Arundel Paul , Alhun Utku , Offiah Amaka C.
Published: April 2022

Background

Achondroplasia is the most common skeletal dysplasia. A significant complication is foramen magnum stenosis. When severe, compression of the spinal cord may result in sleep apnea, sudden respiratory arrest and death. To avoid complications, surgical decompression of the craniocervical junction is offered in at-risk cases. However, practice varies among centres. To standardize magnetic resonance (MR) reporting, the achondroplasia foramen magnum score was recently developed. The reliability of the score has not been assessed.

Objective

To assess the interobserver reliability of the achondroplasia foramen magnum score.

Materials and methods

Base of skull imaging of children with achondroplasia under the care of Sheffield Children’s Hospital was retrospectively and independently reviewed by four observers using the achondroplasia foramen magnum score. Two-way random-effects intraclass coefficient (ICC) was used to assess inter- and intra-observer reliability.

Results

Forty-nine eligible cases and five controls were included. Of these, 10 were scored normal, 17 had a median score of 1 (mild narrowing), 11 had a median score of 2 (effacement of cerebral spinal fluid), 10 had a score of 3 (compression of cord) and 6 had a median score of 4 (cord myelopathic change). Interobserver ICC was 0.72 (95% confidence interval = 0.62–0.81). Intra-observer ICC ranged from 0.60 to 0.86. Reasons for reader disagreement included flow void artefact, subtle T2 cord signal and myelopathic T2 cord change disproportionate to canal narrowing.

Conclusion

The achondroplasia foramen magnum score has good interobserver reliability. Imaging features leading to interobserver disagreement have been identified. Further research is required to prospectively validate the score against clinical outcomes.
Volatile Organic Compounds in the Early Diagnosis of Non‐healing Surgical Wounds: A Systematic Review
Authors: Reeves Nicola , Phillips Samuel , Hughes Aron , Maddocks Sarah , Bates Matthew , Torkington Jared , Robins Lori , Cornish Julie
Published: April 2022

Background

The normal healing of surgical wounds can be disrupted by infection and/or dehiscence, leading to development of chronic, non‐healing wounds (NHW). Diagnosis of NHWs is via clinical acumen and analysis of microbiology wound swabs. Volatile organic compounds (VOCs) are emitted generally by human subjects and specifically as products of bacterial metabolism and are detected in the wound area. This systematic review will assess the potential use of VOCs released by surgical wounds as a non‐invasive method for identifying bacterial species and the progression to NHW.

Method

A systematic search of studies, via PRISMA guidelines, was conducted. Of 220 papers screened, seven studies were included. Outcome data were extracted on methods for VOC analysis and wound/bacterial VOC profiles.

Results

The studies have shown that VOC profiles are identified by two methods: gas chromatography–mass spectrometry and electronic nose. There are VOC profiles associated with causative bacterial species, with early indications that they could be anatomically specific or could monitor treatment effects.

Conclusion

VOC profiling of bacterial species within wounds is possible and could become a point of care test. More research is needed on specific VOC profiles to wound location and whether these profiles may predict progression to NHW.