bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing data‐independent acquisition (DIA) spectral library workflows for plasma proteomics studies
Authors: Rice Shawn J. , Belani Chandra P. 
Published: June 2022

AbstractTraditional data‐independent acquisition (DIA) workflows employ off‐column fractionation with data‐dependent acquisition (DDA) to generate spectral libraries for data extraction. Recent advances have led to the establishment of library‐independent approaches for DIA analyses. The selection of a DIA workflow may affect the outcome of plasma proteomics studies. Here, we establish a gas‐phase fractionation (GPF) workflow to create DIA libraries for DIA with parallel accumulation and serial fragmentation (diaPASEF). This workflow along with three other workflows, fractionated DDA libraries, fractionated DIA libraries, and predicted spectra libraries, were evaluated on 20 plasma samples from nonsmall cell lung cancer patients with low or high levels of IL‐6. We sought to optimize protein identification and total experiment time. The novel GPF workflow for diaPASEF outperformed the traditional ddaPASEF workflow in the number of identified and quantified proteins. A library‐independent workflow based on predicted spectra identified and quantified the most proteins in our experiment at the cost of computational power. Overall, the choice of DIA library workflow seemed to have a limited effect on the overall outcome of a plasma proteomics experiment, but it can affect the number of proteins identified and the total experiment time.
Ca2+‐induced structural changes and intramolecular interactions in N‐terminal region of diacylglycerol kinase alpha
Authors: Takahashi Daisuke , Yonezawa Kento , Okizaki Yuki , Caaveiro Jose M. M. , Ueda Tadashi , Shimada Atsushi , Sakane Fumio , Shimizu Nobutaka 
Published: June 2022

AbstractDiacylglycerol kinases (DGKs) are multi‐domain lipid kinases that modulate the levels of lipid messengers, diacylglycerol, and phosphatidic acid. Recently, increasing attention has been paid to its α isozyme (DGKα) as a potential target for cancer immunotherapy. However, little progress has been made on the structural biology of DGKs, and a detailed understanding of the Ca2+‐triggered activation of DGKα, for which the N‐terminal domains likely play a critical role, remains unclear. We have recently shown that Ca2+ binding to DGKα‐EF induces conformational changes from a protease‐susceptible “open” conformation in the apo state to a well‐folded one in its holo state. Here, we further studied the structural properties of DGKα N‐terminal (RVH and EF) domains using a series of biophysical techniques. We first revealed that the N‐terminal RVH domain is a novel Ca2+‐binding domain, but the Ca2+‐induced conformational changes mainly occur in the EF domain. This was corroborated by NMR experiments showing that the EF domain adopts a molten‐globule like structure in the apo state. Further analyses using SEC‐SAXS and NMR indicate that the partially unfolded EF domain interacts with RVH domain, likely via hydrophobic interactions in the absence of Ca2+, and this interaction is modified in the presence of Ca2+. Taken together, these results present novel insights into the structural rearrangement of DGKα N‐terminal domains upon binding to Ca2+, which is essential for the activation of the enzyme.
The free energy folding penalty accompanying binding of intrinsically disordered α‐helical motifs
Authors: Hadži San , Lah Jurij 
Published: June 2022

AbstractIntrinsically disordered proteins (IDPs) are abundant in eukaryotic proteomes and preform critical roles in many cellular processes, most often through the association with globular proteins. Despite lacking a stable three‐dimensional structure by themselves, they may acquire a defined conformation upon binding globular targets. The most common type of secondary structure acquired by these binding motifs entails formation of an α‐helix. It has been hypothesized that such disorder‐to‐order transitions are associated with a significant free energy penalty due to IDP folding, which reduces the overall IDP‐target affinity. However, the exact magnitude of IDP folding penalty in α‐helical binding motifs has not been systematically estimated. Here, we report the folding penalty contributions for 30 IDPs undergoing folding‐upon‐binding and find that the average IDP folding penalty is +2.0 kcal/mol and ranges from 0.7 to 3.5 kcal/mol. We observe that the folding penalty scales approximately linearly with the change in IDP helicity upon binding, which provides a simple empirical way to estimate folding penalty. We analyze to what extent do pre‐structuring and target‐bound IDP dynamics (fuzziness) reduce the folding penalty and find that these effects combined, on average, reduce the folding cost by around half. Taken together, the presented analysis provides a quantitative basis for understanding the role of folding penalty in IDP‐target interactions and introduces a method estimate this quantity. Estimation and reduction of IDP folding penalty may prove useful in the rational design of helix‐stabilized inhibitors of IDP‐target interactions.StatementThe α‐helical binding motifs are ubiquitous among the intrinsically disordered proteins (IDPs). Upon binding their targets, they undergo a disorder‐to‐order transition, which is accompanied by a significant folding penalty whose magnitude is generally not known. Here, we use recently developed statistical‐thermodynamic model to estimate the folding penalties for 30 IDPs and clarify the roles of IDP pre‐folding and bound‐state dynamics in reducing the folding penalty.
Comparison of herbicide specificity of CYP81A cytochrome P450s from rice and a multiple‐herbicide resistant weed, Echinochloa phyllopogon
Authors: Ha Woosuk , Yamaguchi Takuya , Iwakami Satoshi , Sunohara Yukari , Matsumoto Hiroshi 
Published: June 2022

AbstractBACKGROUNDCYP81A cytochrome P450s (CYP81As) play a key role in herbicide detoxification in Poaceae plants. Crop CYP81As confer natural tolerance to multiple herbicides, whereas CYP81As in weeds disrupt herbicide action. Identifying differences in CYP81A herbicide specificity between crops and weeds could provide valuable information for controlling weeds. In this study, we quantitatively compared herbicide specificity between CYP81A6 from rice (Oryza sativa) and CYP81A12 and CYP81A21 from a weed, Echinochloa phyllopogon, using transgenic Escherichia coli and Arabidopsis.RESULTSAll three CYP81As metabolized the five tested herbicides and formed similar metabolites, with the highest relative activities of 400 to 580% toward bentazone compared to their activity on bensulfuron‐methyl (defined as 100%). However, they showed differing activity toward propyrisulfuron. The relative activities of Echinochloa phyllopogon CYP81A12 (12.2%) and CYP81A21 (34.4%) toward propyrisulfuron were lower than that of rice CYP81A6 (98.5%). Additionally, rice CYP81A6 produced O‐demethylated propyrisulfuron and hydroxylated products, whereas Echinochloa phyllopogon CYP81As produced only hydroxylated products. Arabidopsis expressing CYP81A12 and CYP81A21 exhibited lower levels of resistance against propyrisulfuron compared to that in Arabidopsis expressing CYP81A6. Homology modeling and in silico docking revealed that bensulfuron‐methyl docked well into the active centers of all three CYP81As, whereas propyrisulfuron docked into rice CYP81A6 but not into Echinochloa phyllopogon CYP81As.CONCLUSIONThe differing herbicide specificity displayed by rice CYP81A6 and Echinochloa phyllopogon CYP81A12 and CYP81A21 will help design inhibitors (synergists) of weed CYP81As, as well as develop novel herbicide ingredients that are selectively metabolized by crop CYP81As, to overcome the problem of herbicide resistance. © 2022 Society of Chemical Industry.
Targeting the microRNA pathway core genes, Dicer 1 and Argonaute 1, negatively affects the survival and fecundity of Bemisia tabaci
Authors: Bidari Farzad , Fathipour Yaghoub , Asgari Sassan , Mehrabadi Mohammad 
Published: June 2022

AbstractBACKGROUNDMicroRNAs (miRNAs) are small regulatory non‐coding RNAs that are involved in a variety of biological processes such as immunity, cell signaling and development by regulating gene expression. The whitefly Bemisia tabaci is a polyphagous vector that transmits many plant viruses causing economic damage to crops worldwide. In this study, we characterized and analyzed the expression of the miRNA core genes Argonaute‐1 (Ago1) and Dicer‐1 (Dcr1) in B. tabaci and explored the effect of their silencing on the insect's fitness.RESULTSOur results showed that Ago1 and Dcr1 are differentially expressed in different tissues and developmental stages of B. tabaci. To determine the function of the miRNA pathway in B. tabaci, we silenced Ago1 and Dcr1 using specific double‐stranded RNAs to the genes. RNA interference (RNAi) of Ago1 and Dcr1 decreased the expression level of the core genes and reduced the abundance of Let‐7 and miR‐184 miRNAs. Silencing of the miRNA pathway core gene also negatively affected the biology of B. tabaci by reducing fertility, fecundity and survival of this insect pest.CONCLUSIONSTogether, our results showed that silencing the miRNA pathway core genes reduced the miRNA levels followed by reduced fecundity and survival of B. tabaci, which highlighted the importance of the miRNA pathway in this insect. The miRNA core genes are attractive targets for developing an RNAi‐based strategy for targeting this notorious insect pest. © 2022 Society of Chemical Industry.
Multi‐model averaging improves the performance of model‐guided infliximab dosing in patients with inflammatory bowel diseases
Authors: Kantasiripitak Wannee , Outtier An , Wicha Sebastian G. , Kensert Alexander , Wang Zhigang , Sabino João , Vermeire Séverine , Thomas Debby , Ferrante Marc , Dreesen Erwin 
Published: June 2022

AbstractInfliximab dosage de‐escalation without prior knowledge of drug concentrations may put patients at risk for underexposure and trigger the loss of response. A single‐model approach for model‐informed precision dosing during infliximab maintenance therapy has proven its clinical benefit in patients with inflammatory bowel diseases. We evaluated the predictive performances of two multi‐model approaches, a model selection algorithm and a model averaging algorithm, using 18 published population pharmacokinetic models of infliximab for guiding dosage de‐escalation. Data of 54 patients with Crohn’s disease and ulcerative colitis who underwent infliximab dosage de‐escalation after an earlier escalation were used. A priori prediction (based solely on covariate data) and maximum a posteriori prediction (based on covariate data and trough concentrations) were compared using accuracy and precision metrics and the classification accuracy at the trough concentration target of 5.0 mg/L. A priori prediction was inaccurate and imprecise, with the lowest classification accuracies irrespective of the approach (median 59%, interquartile range 59%–63%). Using the maximum a posteriori prediction, the model averaging algorithm had systematically better predictive performance than the model selection algorithm or the single‐model approach with any model, regardless of the number of concentration data. Only a single trough concentration (preferably at the point of care) sufficed for accurate and precise prediction. Predictive performance of both single‐ and multi‐model approaches was robust to the lack of covariate data. Model averaging using four models demonstrated similar predictive performance with a five‐fold shorter computation time. This model averaging algorithm was implemented in the TDMx software tool to guide infliximab dosage de‐escalation in the forthcoming prospective MODIFI study (NCT04982172).
Ursolic acid inhibits the activation of smoothened‐independent non‐canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade
Authors: Chen Li , Liu Maolun , Yang Han , Ren Shan , Sun Qiang , Zhao Hui , Ming Tianqi , Tang Shun , Tao Qiu , Zeng Sha , Meng Xianli , Xu Haibo 
Published: June 2022

AbstractIt is being brought to light that smoothened (SMO)‐independent non‐canonical Hedgehog signaling is associated with the pathogenesis of various cancers. Ursolic acid (UA), a pentacyclic triterpenoid present in many medicinal herbs, manifests potent effectiveness against multiple malignancies including colorectal cancer (CRC). In our previous study, UA was found to protect against CRC in vitro by suppression of canonical Hedgehog signaling cascade. Here, the influence of UA on SMO‐independent non‐canonical Hedgehog signaling in CRC was investigated in the present study, which demonstrated that UA hampered the proliferation and migration, induced the apoptosis of HCT‐116hSMO− cells with SMO gene knockdown, accompanied by the augmented expression of the suppressor of fused (SUFU), and lessened levels of MYC (c‐Myc), glioma‐associated oncogene (GLI1) and Sonic Hedgehog (SHH), and lowered phosphorylation of protein kinase B (PKB, AKT), suggesting that UA diminished non‐canonical Hedgehog signal transduction in CRC. In HCT‐116hSMO− xenograft tumor, UA ameliorated the symptoms, impeded the growth and caused the apoptosis of CRC, with heightened SUFU expression, and abated levels of MYC, GLI1, and SHH, and mitigated phosphorylation of AKT, indicating that UA down‐regulated non‐canonical Hedgehog signaling cascade in CRC. Taken together, UA may alleviate CRC by suppressing AKT signaling‐dependent activation of SMO‐independent non‐canonical Hedgehog pathway.
Accounting for Lambertian reflection in the assimilation of microwave sounding radiances over snow and sea‐ice
Authors: Bormann Niels 
Published: June 2022

AbstractThis article investigates two aspects aimed at an increased use of surface‐sensitive microwave sounding radiances for numerical weather prediction (NWP), namely the assimilation of humidity‐sounding radiances from the Advanced Technology Microwave Sounder (ATMS) over snow, as well as the use of Lambertian reflection in radiative‐transfer modelling over snow and sea‐ice surfaces for temperature‐ and humidity‐sounding radiances. The Lambertian characteristics are modelled through a parameterisation of the effective zenith angle used to calculate the downwelling radiation in the radiative‐transfer model. Using Lambertian rather than specular reflection improves the forward modelling significantly for 183‐GHz humidity‐sounding channels over snow and sea‐ice in comparisons with observations, including a reduction of significant zenith‐angle‐dependent biases. For temperature‐sounding channels in the 50‐GHz band, comparisons between observations and background equivalents also suggest improvements from treating snow and sea‐ice surfaces as Lambertian or semi‐Lambertian, but the characteristics appear more variable and there are indications of other sources of error, such as biases in the skin temperature. For both spectral regions, the improvement from using nonspecular reflection is clearest for snow‐covered land surfaces. Assimilation experiments show that the addition of 183‐GHz humidity‐sounding channels from ATMS over snow‐covered land leads to a slight positive impact over higher latitudes in winter. On top of this, replacing the specular surface assumption over snow and sea‐ice with a fully Lambertian one for 183‐GHz channels on ATMS and semi‐Lambertian one for 50‐GHz channels on ATMS and the Advanced Microwave Sounding Unit–A (AMSU‐A) means that more observations pass quality control, giving a neutral to slightly positive impact at higher latitudes in winter. Combining the two changes leads to small forecast benefits that are statistically significant up to day 3 at higher latitudes.
Comprehensive metabolite identification study of arterolane using hydrophilic interaction liquid chromatography with quadrupole‐time‐of‐flight mass spectrometry
Authors: Niguram Prakash , Kate Abhijeet S. 
Published: June 2022

RationaleIn 2012, arterolane (ART) in combination with piperaquine received approval in India for the treatment of plasmodium‐induced malaria; however, to date, a detailed metabolite identification study of ART has not been reported. Being polar in nature, ART shows early elution on reversed‐phase columns which might be the rate‐limiting factor of its systematic analytical studies. We have utilized hydrophilic interaction liquid chromatography (HILIC) to separate in vitro and in vivo metabolites of ART.MethodsThe possible sites of metabolism were predicted by XenoSite software to obtain an initial assessment. In vitro studies were conducted by incubating the drug with liver microsomes such as human, rat and human S9 fractions. Later, in vivo studies were performed to check the metabolites in urine, faeces and plasma. The samples were pooled and subjected to the protein precipitation method before analysis by liquid chromatography/quadrupole‐time‐of‐flight mass spectrometry (LC/QTOFMS).ResultsWe have observed 15 metabolites in this study which were phase I metabolites formed due to hydroxylation, dihydroxylation, peroxide bond scission and oxidation. Here, we report 11 metabolites of ART for the first time. The metabolic pathways and plausible structures were proposed according to accurate mass measurements and its MS/MS data.ConclusionsThe present study comprehensively reports the in vitro and in vivo metabolism of ART mentioning 11 novel metabolites. Here, extensive use of HILIC has helped to efficiently separate various metabolites. These findings would help prospects of ART disposition and its congeners.
Global stabilization for a class of upper‐triangular stochastic nonlinear systems with input delay via sampled‐data output feedback
Authors: Mao Jun , Zou Wencheng , Guo Jian , Xiang Zhengrong 
Published: June 2022

AbstractThe contribution of this investigation lies in solving a sampled‐data output feedback stabilization problem for a class of upper‐triangular stochastic nonlinear systems in ‐normal structure with unavailable states and uncertain time‐varying input delay. A reduced‐order observer with the available sampled output detection is developed for the focused system to estimate its unavailable states, and under such observer, a sampled‐data output feedback stabilizer is constructed by combining the backstepping and adding a power integral techniques. Through selecting the appropriate Lyapunov–Krasovskii functionals, we can demonstrate that the adverse influences caused by the uncertain time‐varying delays in the resulting closed‐loop system can be restricted effectively by the constructed stabilizer, and further, by following the stochastic differential theories, the global stability of the considered resulting closed‐loop system can be analyzed under the suitable design parameters and allowable sampling period. Finally, two examples are given to verify the effectiveness of the proposed control method.
Robust adaptive control Lyapunov‐barrier function for non‐collocated control and safety of underactuated robotic systems
Authors: Azimi Vahid , Hutchinson Seth 
Published: June 2022

AbstractQuadratic program‐based control Lyapunov‐control barrier function (QP‐CLBF) is a recently developed control scheme that balances stability and safety in an optimal fashion. However, direct application of such controllers to uncertain nonlinear systems with model uncertainties and disturbances could potentially degrade the performance of closed‐loop systems and violate/restrict safety‐critical constraints. This article presents a novel robust QP‐based adaptive approach for non‐collocated control of a class of underactuated robotic systems with a semi‐strict‐feedback form through which exponential disturbance‐to‐error (eDE) stability of all system solutions is ensured. We begin by developing a backstepping design technique based on which a neural network‐based adaptive control is designed to approximate unknown nonlinear functions. To compensate for uncanceled uncertainties, including modeling approximation error, chained error effects between coordinates, and disturbances, virtual inputs are designed whose gains are evolved by projection‐based adaptation mechanisms. To construct a three‐term control law, including feedforward, adaptive, and optimal terms, a QP optimization problem is synthesized to compute a family of optimal stabilizing signals while encoding time‐varying robust CLF (TVRCLF) and CBF (TVRCBF), and control bounds as constraints. In contrast with existing QP‐CLBF, our control technique with the proposed TVRCLF and TVRCBF significantly improves control objectives and strictly guarantees safety by automatically compensating for unknown uncertainties without the need for knowing their bounds a priori. The eDE stability of all system errors is proven using Lyapunov stability arguments for both collocated and non‐collocated coordinates. Simulations and comparisons to a baseline QP‐CLBF‐based feedback linearization (QP‐CLBF/FL) on a single‐link flexible‐joint robot verify the benefits of the proposed control approach.
Epidural catheter misplacement and knot formation within the hypoaxial musculature of a dog
Authors: Martinez i Ferré Bernat , Corletto Federico , Shing Hannah , Bhalla Rebecca 
Published: June 2022

AbstractTechnical complications associated with the use of epidural catheters account for a significant proportion of failures of this technique. Misplacement and knotting of epidural catheters are complications rarely described in both human and veterinary literature. The method used to identify and confirm the correct position of the catheter in the epidural space plays an important role in preventing such complications. However, some of the techniques commonly used can still lead to an equivocal catheter placement. We report a case where loss of resistance, positive analgesic effect and motor deficits of both hindlimbs masked a misplaced epidural catheter in a dog, with knotting of the catheter occurring when removal was attempted.
An Introduction to Digital Transformation
Authors: Mikalef Patrick , Parmiggiani Elena 
Published: June 2022

AbstractDigital transformation has been one of the most studied phenomena in information systems (IS) and organizational science literature. With novel digital technologies emerging at a growing pace, it is important to understand what we have learned in over three decades of research and what we still need to understand in order to harness the full potential of such digital tools. In this chapter, we present a brief overview of digital transformation and develop a conceptual framework which we use as a basis of discussing the extant literature. The conceptual framework is also used as a means of positioning the empirical chapters presented in the rest of this edited volume. Finally, we discuss the role of context in digital transformation and identify some differences that span industry, domain, size class, and country of operation.
Notes on self-dual gravity
Authors: Mao Pujian , Zhao Weicheng 
Published: June 2022

AbstractIn this paper, we study self-dual gravity in the Newman-Penrose formalism. We specify the self-dual solution space from the Newman-Unti solutions. We show that the asymptotic symmetries of the self-dual gravity are still the (extended) BMS symmetries. We transform the self-dual Taub-NUT solution into the Newman-Unti gauge in analytical form.