bluuebunny/crossref_metadata_2025 huggingface dataset:
Saturation mutagenesis of a predicted ancestral Syk‐family kinase
Authors: Hobbs Helen T. , Shah Neel H. , Shoemaker Sophie R. , Amacher Jeanine F. , Marqusee Susan , Kuriyan John
Published: September 2022

Many tyrosine kinases cannot be expressed readily in Escherichia coli, limiting facile production of these proteins for biochemical experiments. We used ancestral sequence reconstruction to generate a spleen tyrosine kinase (Syk) variant that can be expressed in bacteria and purified in soluble form, unlike the human members of this family (Syk and zeta‐chain‐associated protein kinase of 70 kDa [ZAP‐70]). The catalytic activity, substrate specificity, and regulation by phosphorylation of this Syk variant are similar to the corresponding properties of human Syk and ZAP‐70. Taking advantage of the ability to express this novel Syk‐family kinase in bacteria, we developed a two‐hybrid assay that couples the growth of E. coli in the presence of an antibiotic to successful phosphorylation of a bait peptide by the kinase. Using this assay, we screened a site‐saturation mutagenesis library of the kinase domain of this reconstructed Syk‐family kinase. Sites of loss‐of‐function mutations identified in the screen correlate well with residues established previously as critical to function and/or structure in protein kinases. We also identified activating mutations in the regulatory hydrophobic spine and activation loop, which are within key motifs involved in kinase regulation. Strikingly, one mutation in an ancestral Syk‐family variant increases the soluble expression of the protein by 75‐fold. Thus, through ancestral sequence reconstruction followed by deep mutational scanning, we have generated Syk‐family kinase variants that can be expressed in bacteria with very high yield.
Probing the effect of NEK7 and cofactor interactions on dynamics of NLRP3 monomer using molecular simulation
Authors: El‐Sayed Sherihan , Freeman Sally , Bryce Richard A.
Published: September 2022

The NLRP3 inflammasome is a cytoplasmic complex that regulates the activation of inflammatory cytokines and, given its implication in a range of diseases, is an important therapeutic target. The cofactor ATP and the centrosomal kinase NEK7 are important for NLRP3 activation. Here we have constructed and simulated computational models of full‐length monomeric NLRP3 to shed light on the importance of NEK7 and cofactor interactions for its conformation and dynamics in aqueous solution. We find that molecular dynamics simulation reproduces well the features of the recently published cryo‐EM structure of the ADP‐bound NLRP3–NEK7 complex; on the removal of NEK7, the NLRP3 molecule adopts a more compact closed form during simulations. Replacement of ADP by ATP promotes a rearrangement of hydrogen‐bonding interactions, domain interfaces, and a degree of opening of the NLRP3 conformation. We also examine the dynamics of an acidic loop of the LRR domain of NLRP3, which samples in a region observed in the NEK7‐bound cryo‐EM structure but not in an oligomeric form of inactive NLRP3. During the molecular dynamics simulations of NLRP3, we find some plasticity in its topology that suggests access routes for ATP to the cofactor pocket not immediately evident from the existing NEK7‐bound cryo‐EM structure. These computed dynamical trajectories of NLRP3 provide insight into coordinates of deformation that may be key for cofactor binding and inflammasome activation.
Predicted structure of the hepatitis B virus polymerase reveals an ancient conserved protein fold
Authors: Tajwar Razia , Bradley Daniel P. , Ponzar Nathan L. , Tavis John E.
Published: September 2022

Hepatitis B virus (HBV) chronically infects >250 million people. It replicates by a unique protein‐primed reverse transcription mechanism, and the primary anti‐HBV drugs are nucleos(t)ide analogs targeting the viral polymerase (P). P has four domains compared to only two in most reverse transcriptases: the terminal protein (TP) that primes DNA synthesis, a spacer, the reverse transcriptase (RT), and the ribonuclease H (RNase H). Despite being a major drug target and catalyzing a reverse transcription pathway very different from the retroviruses, HBV P has resisted structural analysis for decades. Here, we exploited computational advances to model P. The TP wrapped around the RT domain rather than forming the anticipated globular domain, with the priming tyrosine poised over the RT active site. The orientation of the RT and RNase H domains resembled that of the retroviral enzymes despite the lack of sequences analogous to the retroviral linker region. The model was validated by mapping residues with known surface exposures, docking nucleic acids, mechanistically interpreting mutations with strong phenotypes, and docking inhibitors into the RT and RNase H active sites. The HBV P fold, including the orientation of the TP domain, was conserved among hepadnaviruses infecting rodent to fish hosts and a nackednavirus, but not in other non‐retroviral RTs. Therefore, this protein fold has persisted since the hepadnaviruses diverged from nackednaviruses >400 million years ago. This model will advance mechanistic analyses into the poorly understood enzymology of HBV reverse transcription and will enable drug development against non‐active site targets for the first time.
A methodology for creating mutants of G‐protein coupled receptors stabilized in active state by combining statistical thermodynamics and evolutionary molecular engineering
Authors: Yamamoto Taisei , Yasuda Satoshi , Kasai Rinshi S. , Nakano Ryosuke , Hikiri Simon , Sugaya Kanna , Hayashi Tomohiko , Ogasawara Satoshi , Shiroishi Mitsunori , Fujiwara Takahiro K. , Kinoshita Masahiro , Murata Takeshi
Published: September 2022

We challenged the stabilization of a G‐protein coupled receptor (GPCR) in the active state solely by multiple amino‐acid mutations without the agonist binding. For many GPCRs, the free energy of the active state is higher than that of the inactive state. When the inactive state is stabilized through the lowering of its free energy, the apparent midpoint temperature of thermal denaturation Tm exhibits a significant increase. However, this is not always the case for the stabilization of the active state. We constructed a modified version of our methodology combining statistical thermodynamics and evolutionary molecular engineering, which was recently developed for the inactive state. First, several residues to be mutated are determined using our statistical‐thermodynamics theory. Second, a gene (mutant) library is constructed using Escherichia coli cells to efficiently explore most of the mutational space. Third, for the mutant screening, the mutants prepared in accordance with the library are expressed in engineered Saccharomyces cerevisiae YB14 cells which can grow only when a GPCR mutant stabilized in the active state has signaling function. For the adenosine A2A receptor tested, the methodology enabled us to sort out two triple mutants and a double mutant. It was experimentally corroborated that all the mutants exhibit much higher binding affinity for G protein than the wild type. Analyses indicated that the mutations make the structural characteristics shift toward those of the active state. However, only slight increases in Tm resulted from the mutations, suggesting the unsuitability of Tm to the stability measure for the active state.
Multiple pore lining residues modulate water permeability of GlpF
Authors: Pluhackova Kristyna , Schittny Valentin , Bürkner Paul‐Christian , Siligan Christine , Horner Andreas
Published: September 2022

The water permeability of aquaporins (AQPs) varies by more than an order of magnitude even though the pore structure, geometry, as well as the channel lining residues are highly conserved. However, channel gating by pH, divalent ions or phosphorylation was only shown for a minority of AQPs. Structural and in silico indications of water flux modulation by flexible side chains of channel lining residues have not been experimentally confirmed yet. Hence, the aquaporin “open state” is still considered to be a continuously open pore with water molecules permeating in a single‐file fashion. Using protein mutations outside the selectivity filter in the aqua(glycerol)facilitator GlpF of Escherichia coli we, to the best of our knowledge, for the first time, modulate the position of the highly conserved Arg in the selectivity filter. This in turn enhances or reduces the unitary water permeability of GlpF as shown in silico by molecular dynamics (MD) simulations and in vitro with purified and reconstituted GlpF. This finding suggests that AQP water permeability can indeed be regulated by lipid bilayer asymmetry and the transmembrane potential. Strikingly, our long‐term MD simulations reveal that not only the conserved Arg in the selectivity filter, but the position and dynamics of multiple other pore lining residues modulate water passage through GlpF. This finding is expected to trigger a wealth of future investigations on permeability and regulation of AQPs among others with the aim to tune water permeability for biotechnological applications.
Mapping the interaction between Trim28 and the KRAB domain at the center of Trim28 silencing of endogenous retroviruses
Authors: Taka Jamie R. H. , Sun Yunyuan , Goldstone David C.
Published: September 2022

Transcription of endogenous retroviral elements are tightly regulated during development by members of the KRAB‐containing zinc finger proteins (KRAB‐ZFPs) and the co‐repressor Trim28 (also known as Kap‐1 or Tif1β). KRAB‐ZFPs form the largest family of transcription regulators in mammals and initiate transcriptional silencing by tethering Trim28 to a target locus. Subsequently, Trim28 recruits chromatin modifying effectors resulting in the formation of heterochromatin. In the present study, we identify surface exposed residues on the central six turns of the Trim28 coiled‐coil region forming the binding interface for the KRAB domain. Using AlphaFold2 (AF2) we provide high confidence models of the interface between Trim28 and the KRAB domain and identified leucine 301 on each chain of the Trim28 monomer to act as a pin extending into a hydrophobic pocket on the KRAB domain surface. Site directed mutations in the Trim28‐KRAB binding interface abolished binding to the KRAB domain. Our work provides a detailed understanding of the specific interactions between the KRAB domain and the Trim28 coiled‐coil and how this interaction may be regulated during silencing events.
Acute urinary retention in men: 21‐year trends in incidence, subsequent benign prostatic hyperplasia‐related treatment and mortality: A Danish population‐based cohort study
Authors: Bengtsen Maria Bisgaard , Heide‐Jørgensen Uffe , Borre Michael , Knudsen Jakob S. , Nørgaard Mette
Published: September 2022

Objective

To examine trends in incidence of acute urinary retention, subsequent benign prostatic hyperplasia‐related treatment and mortality in the era of medical therapy for benign prostatic hyperplasia. Additionally, to compare mortality with the general population.

Materials and Methods

We conducted a Danish nationwide registry‐based study including 70,775 men aged 45 years or older with a first hospitalization for acute urinary retention during 1997–2017. We computed annual standardized incidence rates, subsequent 1‐year cumulative incidence of benign prostatic hyperplasia‐related surgical and medical treatment, and standardized 3‐month and 1‐year mortality rates. Finally, we compared standardized all‐cause and cause‐specific mortality ratios with the general population.

Results

The standardized incidence rate of acute urinary retention per 1000 person‐years increased transiently from 2.34 to 3.42 during 1997–2004, but gradually declined to 2.95 in 2017.

The 1‐year cumulative incidence of benign prostatic hyperplasia‐related surgery declined from 31.2% to 19.8% and 20.5% to 7.7% after spontaneous and precipitated acute urinary retention, respectively. During 1997–2017, the standardized 1‐year mortality declined from 22.2% to 17.2%. Compared with the general population, mortality was 4–5 times higher after 3 months and 2–3 times higher after 1 year of acute urinary retention. The cause‐specific standardized mortality ratios were particularly high for deaths attributable to malignancies, urogenital disease, certain infections, chronic pulmonary disease, and diabetes.

Conclusion

During 1997–2017, we observed a transient increase in the incidence of acute urinary retention. The subsequent use of benign prostatic hyperplasia‐related surgery declined considerably and mortality continued to be high, mainly because of deaths from malignancies, urogenital disease, infections, and preexisting comorbidity.
Insecticidal efficacy and risk assessment of different neuropeptide analog combinations against the peach‐potato aphid following topical exposure
Authors: Shi Yan , Li Hao , Nachman Ronald J , Liu Tong‐Xian , Smagghe Guy
Published: September 2022

Background

Insect neuropeptides control essential physiological metabolic activities. In our previous studies, Capability/CAP2b (PK/CAPA) analog 1895 applied alone or as a combination of CAPA analogs (1895 + 2315) was reported to decrease aphid fitness. While this was obtained with the combination of two peptide analogs of the same neuropeptide class, the effect of combining peptide analogs of different neuropeptide classes has not been explored so far.

Results

In this study, we assessed the effect of combinations of the PK/CAPA analog 1895 with neuropeptide analogs of four different classes [adipokinetic hormone (AKH) analog: 2271; myosuppressin analog: 2434; kinin analog: 2460; tachykinin‐related peptide analog: 2463] on the fitness of aphids. We found that the combination of 1895 and AKH analog 2271 was the most effective one to control Myzus persicae. The triple combination 1895 + 2271 + 2315 provided a synergistic effect by further increasing aphid mortality and reducing reproduction relative to 1895 + 2315. Additionally, a biosafety assessment of the combination 1895 + 2271 + 2315 showed no significant lethal nor sub‐lethal effects on survival rates and food intake for the pollinator (Bombus terrestris) and the two representative natural enemies (Harmonia axyridis and Nasonia vitripennis).

Conclusion

These results could facilitate establishment of the triple combination 1895 + 2271 + 2315, and/or inclusion of second generation analogs, as alternatives to broad spectrum and less friendly insecticides. © 2022 Society of Chemical Industry.
Influence of Mg Out‐Diffusion Effect on the Threshold Voltage of GaN‐Based p‐Channel Heterostructure Field‐Effect Transistors
Authors: Niu Xuerui , Ma Xiaohua , Zhang Meng , Yang Ling , Hou Bin , Wu Mei , Jia Fuchun , Zhang Xinchuang , Wang Chong , Hao Yue
Published: September 2022

To resolve the parasitic problems and to fully leverage the superiority of GaN‐based high electron mobility transistors, monolithic integration of different function blocks is a promising solution. The enhancement mode (E‐mode) GaN‐based p‐channel heterostructure field‐effect transistor (p‐HFET) is one of the key components. Herein, the threshold voltage (VTH) is modeled, and the influence of the Mg out‐diffusion effect on VTH is investigated. The impact of the diffusion coefficient of Mg, the Mg concentration in the p‐GaN layer, the thicknesses of the AlGaN layer (tb), p‐GaN channel layer (tch), and an oxide layer (tox) on VTH are all taken into consideration for systematic exploration. The analysis illustrates that lower Mg concentration, smaller diffusion coefficient, and thinner p‐GaN channel and AlGaN layers facilitate the realization of E‐mode p‐HFETs. Furthermore, it can be observed that lower Mg concentration in the p‐GaN layer diminishes the VTH sensitivity to the thickness of the p‐GaN channel layer. Hence, a heterostructure with two p‐GaN layers of different concentrations is suggested to reduce the complexity of the etching technique while improving the ohmic contacts. As a result, the model can effectively guide the design of GaN‐based E‐mode p‐HFETs.
Prioritising students in Assessment for Learning: A scoping review of research on students' classroom experience
Authors: Arnold Julie
Published: September 2022

Assessment for Learning (AfL) is important in policy and practice in secondary schooling across the globe. It is associated with teacher expertise, student agency, a dialogic classroom climate, and a commitment to the needs of all learners. Research about AfL often includes measuring the efficacy of selected practices or foregrounding the role and experience of teachers. Less prominent is literature examining student experience, which is problematic, given AfL's generally agreed aim of orienting learners as evidence seekers, interpreters, and decision‐makers. This scoping review examined 75 empirical studies published since 2002 that provided evidence of the lived experiences of secondary school students when teachers facilitated AfL pedagogical practices. A conceptualisation of student experience as comprising six interrelated dimensions, ranging from recognition of classroom practices to integration with experiences beyond the classroom, is proposed in the thematic arrangement of results. Findings show student experience as responsive to changes in teacher practice when students are co‐practitioners of AfL and developers of disciplinary expertise. The pedagogic power of students as evaluators is affirmed in evidence that positive student evaluation of the worth or value of a practice is an important precondition for productive student experience. AfL further contributes to a generative experience of learning when it enhances dialogic interactions, with students and teachers as partners in moving learning forward. Inclusive AfL and discipline‐specific AfL practices are evident but under‐represented in the field. The video abstract for this article is available athttps://youtu.be/L8HI‐KIskLs.
BOB: Bayesian optimal design for biosimilar trials with co‐primary endpoints
Authors: Chi Xiaohan , Yu Zhangsheng , Lin Ruitao
Published: September 2022

For regulatory approval of a biosimilar product, extensive evaluations should be performed by rigorous clinical trials to establish the similarity between the reference product and the proposed biosimilar in terms of both efficacy and safety. Existing designs for biosimilar trials often use a single primary efficacy endpoint in trial monitoring, and then separately evaluate the safety of the biosimilar product in a secondary analysis at the trial completion. However, ignoring the safety endpoint and the correlation between safety and efficacy in trial monitoring may lead to a high false positive rate, or it may delay the termination of the trial when dissimilarity in safety is early detected. We propose a Bayesian optimal design for biosimilar trials by incorporating both safety and efficacy endpoints in a unified framework. Based on a Bayesian joint safety and efficacy model, we sequentially use a so‐called Bayesian biosimilar probability to make go/no‐go decisions. We calibrate the Bayesian design to maximize the statistical power while maintaining the frequentist type I error rate at the nominal level. We carry out extensive simulation studies to show that the design has desirable performance in terms of the false positive rate and the average sample size. We also apply the proposed design to a biosimilar trial evaluating a ranibizumab product.
Grain Refinement Mechanism of High‐Silicon Steel Based on the Addition of Cr and Ni
Authors: Yu Junbo , Jiang Shuyong , Sun Dong , Yan Bingyao , Lin Peng , Zhang Yanqiu
Published: September 2022

Fe–6.5Si–2Cr–xNi (x = 4, 8, 12) high‐silicon steels with novel chemical composition are fabricated by adding Cr and Ni elements to high‐silicon steels. The experimental results show that the microstructures of FeSiCrNi high‐silicon steels are gradually refined with the increase in Ni content. In particular, as for Fe–6.5Si–2Cr–12Ni sample, the grains are refined very considerably. Fe–6.5Si–2Cr–12Ni sample comprises a large number of A2 disordered phases, a small number of ordered B2 phases, and a certain number of α‐Fe phases. The addition of Ni element inhibits the nucleation of grain boundary ferrite, and thus it contributes to the formation of acicular ferrite with high density of dislocations and high‐angle grain boundaries. In addition, the high content of Ni elements leads to slow diffusion of the atoms as well as severe thermal hysteresis in the Fe–6.5Si–2Cr–12Ni sample. This plays an important role in refining the microstructures of Fe–6.5Si–2Cr–12Ni sample. In addition, the intensity of {001}<100> cube texture and {001}<110> rotation‐cube texture increases with the increase in Ni content, which makes the Fe–6.5Si–2Cr–12Ni sample have strong λ‐fiber texture, α‐fiber texture, and γ‐fiber texture.
A practical approach for monitoring reinforcement corrosion in steel fiber reinforced concrete elements exposed to chloride rich environments
Authors: Gomez Enzo , Leporace‐Guimil Bruno , Conforti Antonio , Plizzari Giovanni , Duffó Gustavo , Zerbino Raul
Published: September 2022

The use of fibers in Reinforced Concrete (RC) elements changes their cracking pattern, leading to narrower and more closely spaced cracks. In addition, the presence of fibers can improve the steel‐to‐concrete bond behavior reducing the steel‐to‐concrete interface damage after cracking. Cracks and steel‐to‐concrete interface damage work like paths, for aggressive agents, to reach the rebar in cracking elements, reducing the initiation period of the corrosion process, and favoring the corrosion at the intersection between cracks and reinforcement. In this context, this article discusses an experimental program on tension ties mechanically cracked and exposed to a chloride‐rich environment with the purpose to check and eventually adequate the typical electrochemical measurements, used in the case of RC elements, for Steel Fiber Reinforced Concrete (SFRC). Adjustments related to degradation morphology and interference of steel fibers are proposed and used on Fiber Reinforced Concrete (FRC) elements for monitoring the influence of cracks and fibers on corrosion propagation. Finally, these proposed modifications were checked and validated against the results obtained by monitoring SFRC beams in the cracked stage.
Romania’s Nature Conservation Reform: A Surprising Convergence with European Law in Response to Societal Concerns
Authors: Martin-Russu Luana
Published: September 2022

To grant more plausibility to the theoretical argument, Martin-Russu includes a second case study in her empirical analysis: an inquiry into Romania’s nature conservation reform and the framework regulating the protection of environmentally significant habitats and species. The evaluation of the legislative performance of the Romanian political elite in the field of nature conservation shows a questionable use of procedures, but this time coupled with a far higher level of responsibility and responsivity to societal concerns.

The chapter reveals a reality at odds with the expectation that limited capacities lead to non-compliance; it shows how the lack of institutional capacities led, through the involvement of civil society actors, to a gradual improvement of EU-driven reforms. Martin-Russu provides a detailed account of how the expansion of protected areas in preparation for EU membership generated an increased need for their effective management, which translated into a legislative solution that allowed civil society organizations and the scientific community to assume responsibility for the administration of protected areas on an equal footing with the government. This, Martin-Russu argues, allowed citizens to pursue their interests through the actions and reactions of civil society, promoting the latter’s growth and gradually strengthening its voice.
Conclusion: Civism Against Cynicism
Authors: Martin-Russu Luana
Published: September 2022

Martin-Russu’s book explains Romania’s reform reversal in the field of public integrity and the fight against corruption by providing evidence of legislative behaviour at the highest levels of policy-making that shows how a highly fragmented domestic political elite pursues private gains by diluting the legislation in force. Her understanding of Europeanization, modelled as a reversible process highly dependent on the interests pursued by political elites, offers a quite pessimistic prospect for reform. However, Martin-Russu suggests a solution to reform instability, found in the empowerment of sectoral civil society to participate, in one manner or another, in the law-making process. Improving the capacities of civil society to participate more effectively in policy formulation and implementation, she argues, makes democratic consolidation more feasible and allows for genuine Europeanizing reform.

Martin-Russu’s book provides a cautionary tale about the naivety of expecting domestic corrupt political elites to lead the fight against corruption, an account of the failure of the EU’s push for reforms to produce genuine and lasting change, and a demonstration of how important it is for the EU to find new ways to support civil society in its member states.
Cooperation Between Automatic and Interactive Software Verifiers
Authors: Beyer Dirk , Spiessl Martin , Umbricht Sven
Published: September 2022

The verification community develops two kinds of verification tools: automatic verifiers and interactive verifiers. There are many such verifiers available, and there is steady progress in research. However, cooperation between the two kinds of verifiers was not yet addressed in a modular way. Yet, it is imperative for the community to leverage all possibilities, because our society heavily depends on software systems that work correctly. This paper contributes tools and a modular design to address the open problem of insufficient support for cooperation between verification tools. We identify invariants as information that needs to be exchanged in cooperation, and we support translation between two ‘containers’ for invariants: program annotations and correctness witnesses. Using our new building blocks, invariants computed by automatic verifiers can be given to interactive verifiers as annotations in the program, and annotations from the user or interactive verifier can be given to automatic verifiers, in order to help the approaches mutually to solve the verification problem. The modular framework, and the design choice to work with readily-available components in off-the-shelf manner, opens up many opportunities to combine new tools from existing components. Our experiments on a large set of programs show that our constructions work, that is, we constructed tool combinations that can solve verification tasks that the verifiers could not solve before.
Daten und Methode: das Forschungsdesign
Authors: Diekmann Isabell
Published: September 2022

Dieses Forschungsvorhaben baut auf einer vorangegangenen Studie auf, deren Daten im Sommer 2016 im Rahmen einer Lehrforschung an der Universität Bielefeld erhoben wurden. Sowohl der neu konzipierte Fragebogen als auch das experimentelle Design sind explizit auf die Forschungsfrage zugeschnitten und reagieren damit auf Probleme, die in der Vergangenheit aufgetreten sind und zu Herausforderungen in der Datenanalyse geführt haben. Zu diesen Herausforderungen zählt etwa die ungleiche Stärke der einzelnen Items, das heißt eine unterschiedlich drastische Formulierung der Items, die einen Vergleich der Zustimmung zu diesen Items schwierig macht.
Lepton flavour violation in hadron decays of the tau lepton within the littlest Higgs model with T-parity
Authors: Pacheco Iván , Roig Pablo
Published: September 2022

Abstract

We first study the hadronic lepton flavor violating tau decays within the littlest Higgs model with T-parity (including one or two pseudoscalars, or a vector resonance). We consider the case where only T-odd particles and partner fermions contribute, and also its extension including Majorana neutrinos coming from an inverse seesaw. In both cases our mean values lie mostly only one order of magnitude below current upper limits, strengthening the case of searching for these decays in the quest for new physics.
Singular Pöschl-Teller II potentials and gravitating kinks
Authors: Zhong Yuan
Published: September 2022

Abstract

We report a two-dimensional (2D) gravitating kink model, for which both the background field equations and the linear perturbation equation are exactly solvable. The background solution describes a sine-Gordon kink that interpolating between two asymptotic AdS2 spaces, and can be regarded as a 2D thick brane world solution. The linear perturbation equation can be recasted into a Schrödinger-like equation with singular Pöschl-Teller II potentials. There is no tachyonic state in the spectrum, so the solution is stable against the linear perturbations. Besides, there can be n = 0, 1, 2,⋯ bounded vibrational modes around the kink. The number of these vibrational modes varies with model parameters.
Detection of Dynamic Phenomena Associated with Underground Nuclear Explosion Using Multiple Seismic Surveys and Machine Learning
Authors: Mathew Shaji , MacBeth Colin , Stevanovic Jenny , Mangriotis Maria-Daphne
Published: September 2022

The application of an active seismic method for detecting the source location of an underground nuclear explosion (UNE) is an ongoing field of research. The objective of active seismic in On-Site Inspection (OSI) is to detect the static signatures such as the cavity created by the UNE. Along with characteristic static signatures, UNEs produce dynamic phenomena such as groundwater mounding, which gradually revert to pre-test conditions. These dynamic phenomena are observable for an extended period, even up to several decades. The magnitude of these phenomena is prominent near the source origin and results from the redistribution of residual energy, such as pressure, temperature, and saturation. These dynamic changes in sub-surface rock and fluid properties will affect the seismic property of the rock, resulting in changes of P-wave velocity. These changes can be detected by using an active seismic survey. This study highlights the potential of using time-lapse seismic to identify ground zero by monitoring post-explosion variation in the seismic signature. Time-lapse seismic, also known as 4D seismic, is a well-known technology, used in the oil and gas industry for several decades for petroleum production monitoring and management. It involves taking more than one 2D/3D survey at different calendar times over the same reservoir and studying the difference in seismic attributes. This study investigates the characteristic dynamic phenomena associated with the UNE and their impact on the emplacement rock’s seismic property. Groundwater mounding (GWM) is one of the phenomena with a high gradient of dissipation during the initial days immediately after the explosion. We look at the impact of GWM variation on seismic P-wave velocity and discuss the potential of using time-lapse seismic for its detection. The challenges of implementing time-lapse seismic, such as non-repeatability, seasonal variations and time constraints, are discussed. A frequent seismic monitoring survey method (time-lapse seismic) is proposed to monitor rock and fluid properties changes due to the post-UNE dynamic phenomena. Due to the time constraint for the OSI activity, conventional time-lapse seismic processing would not be suitable. Therefore, a machine learning-based 4D detection workflow is presented. The near-real-time 4D detection workflow using machine learning can be implemented during the OSI to identify the source location or ground zero.
Predicting the Timing of Catastrophic Failure During Triaxial Compression: Insights from Discrete Element Method Simulations
Authors: McBeck Jessica
Published: September 2022

Examining the deformation of rocks during triaxial compression may provide insights into the precursory phase that leads to large earthquakes by revealing the components of the deformation field that evolve with predictable, systematic behavior preceding catastrophic failure. Here, we build three-dimensional discrete element method simulations of the triaxial compression of rock cores that include a variety of fault geometries in order to identify the components of the deformation field, including the velocity and strain components, that enable machine learning models to predict the timing of macroscopic failure. The results suggest that the velocity field provides more valuable information about the timing of macroscopic failure than the strain field, and in particular, the velocity component parallel to the maximum compression direction. The models also strongly depend on the second invariant of the strain deviator tensor,$${J}_{2}$$J2, indicative of the shear strain. The importance of$${J}_{2}$$J2on the model predictions increases with confining stress, consistent with laboratory observations that show a transition from tensile- to shear-dominated deformation with increasing confining stress. In contrast to expectations from previous machine learning analyses, none of the models strongly depend on components of the strain tensor indicative of dilation, such as the first invariant of the strain tensor. This difference may arise because the simulations host less dilative strain than the experimental rocks.
Percutaneously inserted ventriculo-ureteral shunt as a salvage treatment in paediatric hydrocephalus: a technical note
Authors: Sandvik Ulrika , Bartek Jiri , Edström Erik , Jönsson Mattias , Stenman Jakob
Published: September 2022

Background

Hydrocephalus is a challenge for paediatric neurosurgeons. When the abdominal cavity and heart fail as diversion sites for cerebrospinal fluid (CSF), many of the otherwise used alternative diversion sites are not feasible due to the smaller physical body size of children and infants. Using the urinary system as a site of diversion has been described in adults primarily.

Objective

To describe a minimally invasive procedure to percutaneously access the ureter for placement of a distal catheter in the treatment of paediatric hydrocephalus.

Methods

A percutaneous ultrasound-assisted technique was used to access the renal pelvis for catheter placement into the distal ureter.

Results

Fifteen months after the surgery, the child has a stable neurological condition and adequately managed hydrocephalus.

Conclusion

The urinary tract should be considered a viable option for CSF diversion in complex paediatric hydrocephalus. A multidisciplinary approach consisting of interventional radiologists, urologists and neurosurgeons should be involved in the evaluation of potential candidates.
Food insecurity and physical multimorbidity among adults aged ≥ 50 years from six low- and middle-income countries
Authors: Smith Lee , Shin Jae Il , Jacob Louis , López Sánchez Guillermo F. , Schuch Felipe , Tully Mark A. , Oh Hans , Veronese Nicola , Soysal Pinar , Butler Laurie , Barnett Yvonne , Koyanagi Ai
Published: September 2022

Purpose

Food insecurity and multimoribidity (i.e., ≥ 2 chronic conditions) may be linked bidirectionally, but there are no studies on this topic from LMICs. Therefore, the aim of the present study was to examine the association between food insecurity and physical multimorbidity in a large representative sample of older adults from six LMICs.

Methods

Cross-sectional, community-based data on adults aged ≥ 50 years from the World Health Organization’s Study on Global AGEing and Adult Health (SAGE) conducted in China, Ghana, India, Mexico, Russia, and South Africa were analyzed. A total of 11 chronic physical conditions were assessed. Past 12 month food insecurity was assessed with two questions on frequency of eating less and hunger due to lack of food. Multivariable logistic regression analysis was conducted to assess the associations.

Results

Data on 34,129 adults aged ≥ 50 years [mean (SD) age 62.4 (16.0) years; age range 50–114 years; 47.9% males] were analyzed. After adjustment for potential confounders, in the overall sample, compared to being food secure, moderate and severe food insecurity were associated with 1.29 (95% CI 1.06–1.56) and 1.56 (95% CI 1.13–2.16) times higher odds for multimorbidity, respectively

Conclusion

Food insecurity was associated with greater odds for multimorbidity in older adults from LMICs. Addressing food insecurity in the general population may reduce risk for multimorbidity, while screening for food insecurity and addressing it among those with multimorbidity may lead to better clinical outcomes, pending future longitudinal research
Fe2+–Mg partitioning between olivine and liquid at low oxygen fugacity: an experimental and thermodynamic framework
Authors: Saper L. M. , Baker M. B. , Stolper E. M.
Published: September 2022

A set of 1-atm gas-mixing experiments (n = 31) was run using Re wire loops at low-oxygen fugacity (ƒO2, within one half-log unit of the Fe–FeO buffer) and temperatures of 1175–1400 °C to explore the compositional dependence of the Fe2+–Mg olivine–liquid exchange coefficient, $${\mathrm{K}}_{\mathrm{D},{\mathrm{Fe}}^{2+}-\mathrm{Mg}}^{\mathrm{ol}/\mathrm{liq}}$$

K

D
,

Fe

2
+

-
Mg

ol
/
liq

, under conditions where corrections for liquid Fe3+ are small. The bulk compositions used for these experiments include a picrite, a high-alumina basalt, and a suite of three MORB compositions with variable Fe/Mg. The $${\mathrm{K}}_{\mathrm{D},{\mathrm{Fe}}^{2+}-\mathrm{Mg}}^{\mathrm{ol}/\mathrm{liq}}$$

K

D
,

Fe

2
+

-
Mg

ol
/
liq

 values from the n = 14 experiments run on pre-saturated Re wire loops were fit to a regular solution model that relates $${\mathrm{K}}_{\mathrm{D},{\mathrm{Fe}}^{2+}-\mathrm{Mg}}^{\mathrm{ol}/\mathrm{liq}}$$

K

D
,

Fe

2
+

-
Mg

ol
/
liq

 to temperature, melt composition, and olivine composition. Fe2+–Mg exchange in the experiments is well-described using two parameters: the SiO2 content of the liquid and the coexisting olivine composition. Combining our experiments with a literature compilation of low-pressure, low-ƒO2 experiments (largely on non-terrestrial bulk compositions) produced a combined data set spanning a broad region of composition space (e.g., liquid TiO2 and Na2O + K2O contents up to 18.4 wt% and 8.4 wt%, respectively). Fitting this expanded experimental database required two additional liquid compositional terms: Ti, and a Si-(Na + K) cross-term. Because the Fe3+ content of all of the experimental liquids is low, the compositional variation seen in $${\mathrm{K}}_{\mathrm{D},{\mathrm{Fe}}^{2+}-\mathrm{Mg}}^{\mathrm{ol}/\mathrm{liq}}$$

K

D
,

Fe

2
+

-
Mg

ol
/
liq

is effectively independent of the compositional effects on liquid Fe3+/Fe2+ ratios. Given olivine–liquid Mg or Fe2+ partition coefficient information, it is possible to eliminate the explicit dependence of $${\mathrm{K}}_{\mathrm{D},{\mathrm{Fe}}^{2+}-\mathrm{Mg}}^{\mathrm{ol}/\mathrm{liq}}$$

K

D
,

Fe

2
+

-
Mg

ol
/
liq

 on olivine composition, enabling a simple iterative approach for calculating the composition of coexisting olivine given only the bulk composition (and Fe3+/Fe2+ ratio) of an olivine-saturated liquid.
Short-term outcomes of colorectal cancer surgery in older patients: a novel nomogram predicting postoperative morbi-mortality
Authors: Moro-Valdezate David , Martín-Arévalo José , Ferro-Echevarría Óscar , Pla-Martí Vicente , García-Botello Stephanie , Pérez-Santiago Leticia , Gadea-Mateo Ricardo , Tarazona Noelia , Roda Desamparados , Roselló-Keränen Susana , Espí-Macías Alejandro
Published: September 2022

Purpose

To analyze short-term outcomes of curative-intent cancer surgery in all adult patients diagnosed with colorectal cancer undergoing surgery from January 2010 to December 2019 and determine risk factors for postoperative complications and mortality.

Methods

Retrospective study conducted at a single tertiary university institution. Patients were stratified by age into two groups: < 75 years and ≥ 75 years. Primary outcome was the influence of age on 30-day complications and mortality. Independent risk factors for postoperative adverse events or mortality were analyzed, and two novel nomograms were constructed.

Results

Of the 1486 patients included, 580 were older (≥ 75 years). Older subjects presented more comorbidities and tumors were located mainly in right colon (45.7%). After matching, no between-group differences in surgical postoperative complications were observed. The 30-day mortality rate was 5.3% for the older and 0.8% for the non-older group (p < 0.001). In multivariable analysis, the independent risk factors for postoperative complications were peripheral vascular disease, chronic pulmonary disease, severe liver disease, postoperative transfusion, and surgical approach. Independent risk factors for 30-day mortality were age ≥ 80 years, cerebrovascular disease, severe liver disease, and postoperative transfusion. The model was internally and externally validated, showing high accuracy.

Conclusion

Patients aged ≥ 75 years had similar postoperative complications but higher 30-day mortality than their younger counterparts. Patients with peripheral vascular disease, chronic pulmonary disease, or severe liver disease should be informed of higher postoperative complications. But patients aged ≥ 80 suffering cerebrovascular disease, severe liver disease, or needing postoperative transfusion should be warned of significantly increased risk of postoperative mortality.
Contextual determinants associated with children’s and adolescents’ mental health care utilization: a systematic review
Authors: Verhoog S. , Eijgermans D. G. M. , Fang Y. , Bramer W. M. , Raat H. , Jansen W.
Published: September 2022

Determinants at the contextual level are important for children’s and adolescents’ mental health care utilization, as this is the level where policy makers and care providers can intervene to improve access to and provision of care. The objective of this review was to summarize the evidence on contextual determinants associated with mental health care utilization in children and adolescents. A systematic literature search in five electronic databases was conducted in August 2021 and retrieved 6439 unique records. Based on eight inclusion criteria, 74 studies were included. Most studies were rated as high quality (79.7%) and adjusted for mental health problems (66.2%). The determinants that were identified were categorized into four levels: organizational, community, public policy or macro-environmental. There was evidence of a positive association between mental health care utilization and having access to a school-based health center, region of residence, living in an urban area, living in an area with high accessibility of mental health care, living in an area with high socio-economic status, having a mental health parity law, a mental health screening program, fee-for-service plan (compared to managed care plan), extension of health insurance coverage and collaboration between organizations providing care. For the other 35 determinants, only limited evidence was available. To conclude, this systematic review identifies ten contextual determinants of children’s and adolescents’ mental health care utilization, which can be influenced by policymakers and care providers. Implications and future directions for research are discussed

PROSPERO ID: CRD42021276033.
Multifactor analysis of specific storage estimates and implications for transient groundwater modelling
Authors: Chowdhury Faysal , Gong Jinzhe , Rau Gabriel C. , Timms Wendy A.
Published: September 2022

Specific storage (SS) has considerable predictive importance in the modelling of groundwater systems, yet little is known about its statistical distribution and dependency on other hydrogeological characteristics. This study provides a comprehensive overview and compiles 430 values of SS from 183 individual studies, along with complementary hydrogeological information such as estimation methods, lithology, porosity, and formation compressibility. Further evaluation of different approaches to determine and utilize SS values for numerical groundwater modelling, along with the scale and source of uncertainty of different measurement methods, was carried out. Overall, SS values range across six orders of magnitude (from 3.2 × 10–9 to 6 × 10–3 m–1) with a geometric mean of 1.1 × 10–5 m–1 and the majority (> 67%) of values are in the order of 10–5 and 10–6 m–1. High SS values of ~10–4 m–1 were reported for glacial till and sandy lithologies, particularly for shallow and thin strata where leakage may obscure the estimation of SS. A parallel assessment of 45 transient regional-scale groundwater models reveals a disconnect between findings of this study and the way SS is treated in practice, and that there is a lack of foundational SS data to conduct quantitative uncertainty analysis. This study provides the first probability density functions of SS for a variety of lithology types based on the field and laboratory tests collated from the literature. Log transformed SS values follow a Gaussian/normal distribution which can be applied to evaluate uncertainties of modelling results and therefore enhance confidence in the groundwater models that support decision making.
Evaluation of laboratory predictors for intravenous immunoglobulin resistance and coronary artery aneurysm in Kawasaki Disease before and after therapy
Authors: Liu Jie , Ye Bingbing , Su Danyan , Qin Suyuan , Zhao Weiying , Pang Yusheng
Published: September 2022

Objectives

We aimed to evaluate the clinical and laboratory characteristics of patients with Kawasaki disease (KD) before and after therapy.

Methods

Patients with KD were divided into different groups according to their responsiveness to initial intravenous immunoglobulin (IVIG) treatment and coronary status. The clinical and laboratory parameters before and after therapy were compared. Multivariate analysis was performed to identify the independent risk factors, and the receiver operating characteristic (ROC) curve was applied to assess and compare the prediction ability of risk factors and their fluctuations.

Results

Of the 153 patients included in the study, 41 (26.8%) had IVIG resistance and 37 (24.2%) had developed CAA. After stratifying by therapy response, the two groups differed in the levels of total bilirubin (TSB), albumin, and sodium, neutrophil-to-lymphocyte count ratio (NLR), platelet-to-lymphocyte count ratio (PLR), TSB-to-albumin (B/A) ratio, and prognostic nutritional index (PNI) before IVIG, and in the white blood cell count (WBC), neutrophil count, levels of hemoglobin, C-reactive protein (CRP), alanine aminotransferase (ALT), and albumin, NLR, PNI, capillary leakage index (CLI), and systemic immune-inflammation index (SII) after IVIG. Multivariate analysis revealed that the B/A ratio before IVIG and CLI and SII after IVIG were significantly and positively associated with IVIG resistance and that there was a larger decline in the B/A ratio and smaller decline in CLI and SII pre- and post-treatment in the IVIG-resistant group than in the IVIG-responsive group. However, no statistical differences in the fluctuations of the B/A ratio, CLI, and SII as well as all parameters before and after therapy were observed in patients with and without CAA. ROC curve analyses found a greater AUC value of post-treatment parameters (0.751 and 0.706 for CLI and SII, respectively) compared with pre-treatment parameters (0.654 for B/A ratio) in predicting IVIG resistance; however, the predictive ability of the fluctuations in risk factors before and after therapy was not superior to that of baseline values.

Conclusions

The B/A ratio before IVIG and CLI and SII after IVIG were risk factors for IVIG resistance in patients with KD, independent of CAA development.

Key Points• A high total bilirubin-to-albumin ratio before IVIG and high capillary leakage and systemic immune-inflammation indices after IVIG may indicate an increased risk of intravenous immunoglobulin resistance in patients with Kawasaki disease.• Post-treatment parameters were superior to pre-treatment parameters in terms of prediction; therefore, rapid and repeated assessment of risk factors before and after treatment must be considered in children in whom the vital signs and symptoms do not improve after treatment.