bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective C3d caused by C3 p.W1034R in inherited atypical hemolytic uremic syndrome
Authors: Tsuchida Masafumi , Goto Shin , Watanabe Hirofumi , Goto Sawako , Yamaguchi Hiroki , Narita Ichiei 
Published: October 2023

AbstractIntroductionAtypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy. Personal genome analyses have revealed numerous aHUS‐causing variants, mainly complement‐related genes. However, not all aHUS‐causing variants have been functionally validated.MethodsAn exome sequence analysis of a Japanese multiplex family composed of three patients diagnosed with aHUS in infancy and showing frequent relapses clustered in a dominant transmission mode was performed. Protein interaction between the C3d and C‐terminal domains of factor H was analyzed using a quartz crystal microbalance.ResultsFollowing filtering by heterozygous variants, amino acid substitutions, and allele frequency, the analysis revealed eight rare variants shared by the affected individuals. Variant prioritization listed C3 p.W1034R as the most likely candidate gene mutation in the affected individuals, despite being classified as a variant of uncertain significance. Binding of recombinant C3d harboring 1034R to recombinant short consensus repeats 15 to 20 of factor H was significantly suppressed compared with that of C3 with 1034W.ConclusionC3 p.W1034R results in an inherited form of aHUS that often presents with recurrent episodes, possibly because of impaired interactions between the C3d and C‐terminal domains of factor H. Following comprehensive genomic analysis, functional validation of C3 p.W1034R strengthens the molecular basis for aHUS pathophysiology.
Gender‐dependent multiple cross‐phenotype association of interferon lambda genetic variants with peripheral blood profiles in healthy individuals
Authors: Roy Debarati Guha , Singh Lucky , Chaturvedi Himanshu K. , Chinnaswamy Sreedhar 
Published: October 2023

AbstractBackgroundType III interferons (IFN), also called as lambda IFNs (IFN‐λs), are antiviral and immunomodulatory cytokines that are evolutionarily important in humans. Given their central roles in innate immunity, they could be influencing other aspects of human biology. This study aimed to examine the association of genetic variants that control the expression and/or activity of IFN‐λ3 and IFN‐λ4 with multiple phenotypes in blood profiles of healthy individuals.MethodsIn a cohort of about 550 self‐declared healthy individuals, after applying several exclusion criteria to determine their health status, we measured 30 blood parameters, including cellular, biochemical, and metabolic profiles. We genotyped them at rs12979860 and rs28416813 using competitive allele‐specific PCR assays and tested their association with the blood profiles under dominant and recessive models for the minor allele. IFN‐λ4 variants rs368234815 and rs117648444 were also genotyped or inferred.ResultsWe saw no association in the combined cohort under either of the models for any of the phenotypes. When we stratified the cohort based on gender, we saw a significant association only in males with monocyte (p = 1 × 10−3) and SGOT (p = 7 × 10−3) levels under the dominant model and with uric acid levels (p = 0.01) under the recessive model. When we tested the IFN‐λ4 activity modifying variant within groupings based on absence or presence of one or two copies of IFN‐λ4 and on different activity levels of IFN‐λ4, we found significant (p < 0.05) association with several phenotypes like monocyte, triglyceride, VLDL, ALP, and uric acid levels, only in males. All the above significant associations did not show any confounding when we tested for the same with up to ten different demographic and lifestyle variables.ConclusionsThese results show that lambda interferons can have pleiotropic effects. However, gender seems to be an effect modifier, with males being more sensitive than females to the effect.
Construction, modeling, and control of a three‐beam prototype using interactive fiber rubber composites
Authors: Acevedo‐Velazquez Aline Iobana , Keshtkar Najmeh , Mersch Johannes , Katzer Konrad , Cherif Chokri , Zimmermann Martina , Gerlach Gerald , Röbenack Klaus 
Published: October 2023

AbstractIn this contribution, we discuss the construction, modeling, and control of a three‐beam prototype that utilizes interactive fiber rubber composites integrated with shape memory alloys (SMAs) as actuators. These actuators are integrated into a textile layer and covered with an elastomer layer, providing flexibility and protection to the prototype. A mathematical model was developed to describe the behavior of the prototype, employing system identification techniques. However, precise position control of systems actuated by SMAs is challenging due to their inherent nonlinearities and hysteretic behavior. To tackle this challenge, a proportional‐integral (PI) controller was designed based on robust stability conditions. The effectiveness of the designed PI controller was validated through both numerical simulations and real experiments.
TRIM28 inactivation in epithelial nephroblastoma is frequent and often associated with predisposing TRIM28 germline variants
Authors: Wegert Jenny , Fischer Anne Kristin , Palhazi Balazs , Treger Taryn D , Hilgers Cäcilia , Ziegler Barbara , Jung Hyunchul , Jüttner Eva , Waha Andreas , Fuchs Jörg , Warmann Steven W , Frühwald Michael C , Hubertus Jochen , Pritchard‐Jones Kathy , Graf Norbert , Behjati Sam , Furtwängler Rhoikos , Gessler Manfred , Vokuhl Christian 
Published: October 2023

AbstractWilms tumors (WTs) are histologically diverse childhood cancers with variable contributions of blastema, stroma, and epithelia. A variety of cancer genes operate in WTs, including the tripartite‐motif‐containing‐28 gene (TRIM28). Case reports and small case series suggest that TRIM28 mutations are associated with epithelial morphology and WT predisposition. Here, we systematically investigated the prevalence of TRIM28 inactivation and predisposing mutations in a cohort of 126 WTs with >2/3 epithelial cells, spanning 20 years of biobanking in the German SIOP93‐01/GPOH and SIOP2001/GPOH studies. Overall, 44.4% (56/126) cases exhibited loss of TRIM28 by immunohistochemical staining. Of these, 48 could be further analyzed molecularly, revealing TRIM28 sequence variants in each case – either homozygous (~2/3) or heterozygous with epigenetic silencing of the second allele (~1/3). The majority (80%) of the mutations resulted in premature stops and frameshifts. In addition, we detected missense mutations and small deletions predicted to destabilize the protein through interference with folding of key structural elements such as the zinc‐binding clusters of the RING, B‐box‐2, and PHD domains or the central coiled‐coil region. TRIM28‐mutant tumors otherwise lacked WT‐typical IGF2 alterations or driver events, except for rare TP53 progression events that occurred with expected frequency. Expression profiling identified TRIM28‐mutant tumors as a homogeneous subset of epithelial WTs that mostly present with stage I disease. There was a high prevalence of perilobar nephrogenic rests, putative precursor lesions, that carried the same biallelic TRIM28 alterations in 7/7 cases tested. Importantly, 46% of the TRIM28 mutations were present in blood cells or normal kidney tissue, suggesting germline events or somatic mosaicism, partly supported by family history. Given the high prevalence of predisposing variants in TRIM28‐driven WT, we suggest that immunohistochemical testing of TRIM28 be integrated into diagnostic practice as the management of WT in predisposed children differs from that with sporadic tumors. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Cell‐type‐specific tumour sensitivity identified with a bromodomain targeting PROTAC in adenoid cystic carcinoma
Authors: Rose Alexandra J , Fleming Mercedes M , Francis Jeffrey C , Ning Jian , Patrikeev Anton , Chauhan Ritika , Harrington Kevin J , Swain Amanda 
Published: October 2023

AbstractSalivary gland adenoid cystic carcinoma (ACC) is a rare malignancy with limited treatment options. The development of novel therapies is hindered by a lack of preclinical models. We have generated ACC patient‐derived xenograft (PDX) lines that retain the physical and genetic properties of the original tumours, including the presence of the common MYB::NFIB or MYBL1::NFIB translocations. We have developed the conditions for the generation of both 2D and 3D tumour organoid patient‐derived ACC models that retain MYB expression and can be used for drug studies. Using these models, we show in vitro and in vivo sensitivity of ACC cells to the bromodomain degrader, dBET6. Molecular studies show a decrease in BRD4 and MYB protein levels and target gene expression with treatment. The most prominent effect of dBET6 on tumours in vivo was a change in the relative composition of ACC cell types expressing either myoepithelial or ductal markers. We show that dBET6 inhibits the progenitor function of ACC cells, particularly in the myoepithelial marker‐expressing population, revealing a cell‐type‐specific sensitivity. These studies uncover a novel mechanistic effect of bromodomain inhibitors on tumours and highlight the need to impact both cell‐type populations for more effective treatments in ACC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
A 500‐kW PV generator I–V curve
Authors: Moretón Rodrigo , Lorenzo Eduardo , Muñoz Javier 
Published: October 2023

ABSTRACTThis paper presents the measurement of the I–V curve of a 500‐kW PV generator by means of an own‐made capacitive load. It is shown that I–V curve analysis can also be applied to big PV generators and that when measuring the operation conditions with reference modules and taking some precautions (especially regarding the operation cell temperature), it is still a useful tool for characterizing them and therefore can be incorporated into maintenance procedures. As far as we know, this is the largest I–V curve measured so far. Copyright © 2013 John Wiley & Sons, Ltd.
Retracing the evolution of a modern periplasmic binding protein
Authors: Michel Florian , Romero‐Romero Sergio , Höcker Birte 
Published: October 2023

AbstractInvestigating the evolution of structural features in modern multidomain proteins helps to understand their immense diversity and functional versatility. The class of periplasmic binding proteins (PBPs) offers an opportunity to interrogate one of the main processes driving diversification: the duplication and fusion of protein sequences to generate new architectures. The symmetry of their two‐lobed topology, their mechanism of binding, and the organization of their operon structure led to the hypothesis that PBPs arose through a duplication and fusion event of a single common ancestor. To investigate this claim, we set out to reverse the evolutionary process and recreate the structural equivalent of a single‐lobed progenitor using ribose‐binding protein (RBP) as our model. We found that this modern PBP can be deconstructed into its lobes, producing two proteins that represent possible progenitor halves. The isolated halves of RBP are well folded and monomeric proteins, albeit with a lower thermostability, and do not retain the original binding function. However, the two entities readily form a heterodimer in vitro and in‐cell. The x‐ray structure of the heterodimer closely resembles the parental protein. Moreover, the binding function is fully regained upon formation of the heterodimer with a ligand affinity similar to that observed in the modern RBP. This highlights how a duplication event could have given rise to a stable and functional PBP‐like fold and provides insights into how more complex functional structures can evolve from simpler molecular components.
Identification of natural Rutaecarpine as a potent tobacco mosaic virus (TMV) helicase candidate for managing intractable plant viral diseases
Authors: Li Zhen‐Xing , Hu Jin‐Hong , Luo Rong‐Shuang , Zhang Tai‐Hong , Ding Yue , Zhou Xiang , Liu Li‐Wei , Wu Zhi‐Bing , Yang Song 
Published: October 2023

AbstractBACKGROUNDNaturally occurring alkaloids are particularly suitable for use as pesticide precursors and further modifications due to their cost‐effectiveness, unique mechanism of action, tolerable degradation, and environmental friendliness. The famous tobacco mosaic virus (TMV) is a persistent plant pathogenic virus that can parasitize many plants and severely reduce crop production. To treat TMV disease, TMV helicase acts as a crucial target by hydrolyzing adenosine triphosphate (ATP) to provide energy for double‐stranded RNA unwinding.RESULTSTo seek novel framework alkaloid leads targeting TMV helicase, this work successfully established an efficient screening platform for TMV helicase inhibitors based on natural alkaloids. In vivo activity screening, enzyme activity detection, and binding assays showed that Rutaecarpine from Evodia rutaecarpa (Juss.) Benth exhibited excellent TMV helicase inhibitory properties [dissociation constant (Kd) = 1.1 μm, half maximal inhibitory concentration (IC50) = 227.24 μm] and excellent anti‐TMV ability. Molecular docking and dynamic simulations depicted that Rutaecarpine could stably bind in active pockets of helicase with low binding energy (ΔGbind = −17.8 kcal/mol) driven by hydrogen bonding and hydrophobic interactions.CONCLUSIONGiven Rutaecarpine's laudable bioactivity and structural modifiability, it can serve as a privileged building block for further pesticide discovery.
Evaluation of 30 urban land surface models in the Urban‐PLUMBER project: Phase 1 results
Authors: Lipson Mathew J. , Grimmond Sue , Best Martin , Abramowitz Gab , Coutts Andrew , Tapper Nigel , Baik Jong‐Jin , Beyers Meiring , Blunn Lewis , Boussetta Souhail , Bou‐Zeid Elie , De Kauwe Martin G. , de Munck Cécile , Demuzere Matthias , Fatichi Simone , Fortuniak Krzysztof , Han Beom‐Soon , Hendry Margaret A. , Kikegawa Yukihiro , Kondo Hiroaki , Lee Doo‐Il , Lee Sang‐Hyun , Lemonsu Aude , Machado Tiago , Manoli Gabriele , Martilli Alberto , Masson Valéry , McNorton Joe , Meili Naika , Meyer David , Nice Kerry A. , Oleson Keith W. , Park Seung‐Bu , Roth Michael , Schoetter Robert , Simón‐Moral Andrés , Steeneveld Gert‐Jan , Sun Ting , Takane Yuya , Thatcher Marcus , Tsiringakis Aristofanis , Varentsov Mikhail , Wang Chenghao , Wang Zhi‐Hua , Pitman Andy J. 
Published: October 2023

AbstractAccurately predicting weather and climate in cities is critical for safeguarding human health and strengthening urban resilience. Multimodel evaluations can lead to model improvements; however, there have been no major intercomparisons of urban‐focussed land surface models in over a decade. Here, in Phase 1 of the Urban‐PLUMBER project, we evaluate the ability of 30 land surface models to simulate surface energy fluxes critical to atmospheric meteorological and air quality simulations. We establish minimum and upper performance expectations for participating models using simple information‐limited models as benchmarks. Compared with the last major model intercomparison at the same site, we find broad improvement in the current cohort's predictions of short‐wave radiation, sensible and latent heat fluxes, but little or no improvement in long‐wave radiation and momentum fluxes. Models with a simple urban representation (e.g., ‘slab’ schemes) generally perform well, particularly when combined with sophisticated hydrological/vegetation models. Some mid‐complexity models (e.g., ‘canyon’ schemes) also perform well, indicating efforts to integrate vegetation and hydrology processes have paid dividends. The most complex models that resolve three‐dimensional interactions between buildings in general did not perform as well as other categories. However, these models also tended to have the simplest representations of hydrology and vegetation. Models without any urban representation (i.e., vegetation‐only land surface models) performed poorly for latent heat fluxes, and reasonably for other energy fluxes at this suburban site. Our analysis identified widespread human errors in initial submissions that substantially affected model performances. Although significant efforts are applied to correct these errors, we conclude that human factors are likely to influence results in this (or any) model intercomparison, particularly where participating scientists have varying experience and first languages. These initial results are for one suburban site, and future phases of Urban‐PLUMBER will evaluate models across 20 sites in different urban and regional climate zones.
Multivariable discrete MPC with exponential cost function on the automation of the anesthesia process
Authors: Sandre‐Hernandez Omar , Ramírez‐Barrios Miguel , Ordaz Patricio , Mera Manuel 
Published: October 2023

AbstractThe automation of the delivery of anesthesia infusion rate in a general medical procedure consists of calculating the adequate infusion to regulate a patient's hypnosis state. In this procedure, the patient model has been considered as a Single‐Input Single‐Output system. However, the anesthesiologist introduces other medications, such as analgesics. Therefore, this contribution considers a closed‐loop formulation with two drugs as input control variables: propofol as an anesthetic, and remifentanil as an analgesic. Then, through the mathematical model description, this paper introduces a multiple‐input and multiple‐output (MIMO) model predictive control (MPC) to regulate the deep of hypnosis (DOH) based on the co‐administration of propofol and remifentanil. Since the control variables must be positive during the procedure, the MPC is formulated as a constrained optimization problem. Quadratic programming solves the optimization problem by designing and developing an exponential cost function, which allows the rapid convergence of the MPC optimization algorithm. Finally, the proposed MPC formulation is tested on 12 patients in silico, simulating a 60‐min general surgery. The simulated results verify the performance of the proposed MPC.
Carbonyl‐Supported Coordination in Imidazolates: A Platform for Designing Porous Nickel‐Based ZIFs as Heterogeneous Catalysts
Authors: Škrjanc Aljaž , Jankovič Dominik , Meden Anton , Mazaj Matjaž , Grape Erik Svensson , Gazvoda Martin , Zabukovec Logar Nataša 
Published: October 2023

AbstractZeolitic imidazolate frameworks (ZIFs) are a subclass of metal–organic framework that have attracted considerable attention as potential functional materials due to their high chemical stability and ease of synthesis. ZIFs are usually composed of zinc ions coordinated with imidazole linkers, with some other transition metals, such as Cu(II) and Co(II), also showing potential as ZIF‐forming cations. Despite the importance of nickel in catalysis, no Ni‐based ZIF with permanent porosity is yet reported. It is found that the presence and arrangement of the carbonyl functional groups on the imidazole linker play a crucial role in completing the preferred octahedral coordination of nickel, revealing a promising platform for the rational design of Ni‐based ZIFs for a wide range of catalytic applications. Herein, the synthesis of the first Ni‐based ZIFs is reported and their high potential as heterogeneous catalysts for Suzuki–Miyaura cross‐coupling C─C bond forming reactions is demonstrated.
Carbonaceous Materials‐Based Photothermal Process in Water Treatment: From Originals to Frontier Applications
Authors: Hu Shuyuan , Qin Lei , Yi Huan , Lai Cui , Yang Yang , Li Bisheng , Fu Yukui , Zhang Mingming , Zhou Xuerong 
Published: October 2023

AbstractThe photothermal process has attracted considerable attention in water treatment due to its advantages of low energy consumption and high efficiency. In this respect, photothermal materials play a crucial role in the photothermal process. Particularly, carbonaceous materials have emerged as promising candidates for this process because of exceptional photothermal performance. While previous research on carbonaceous materials has primarily focused on photothermal evaporation and sterilization, there is now a growing interest in exploring the potential of photothermal effect‐assisted advanced oxidation processes (AOPs). However, the underlying mechanism of the photothermal effect assisted by carbonaceous materials remains unclear. This review aims to provide a comprehensive review of the photothermal process of carbonaceous materials in water treatment. It begins by introducing the photothermal properties of carbonaceous materials, followed by a discussion on strategies for enhancing these properties. Then, the application of carbonaceous materials‐based photothermal process for water treatment is summarized. This includes both direct photothermal processes such as photothermal evaporation and sterilization, as well as indirect photothermal processes that assisted AOPs. Meanwhile, various mechanisms assisted by the photothermal effect are summarized. Finally, the challenges and opportunities of using carbonaceous materials‐based photothermal processes for water treatment are proposed.
Survey on security and privacy in Internet of Things‐based eHealth applications: Challenges, architectures, and future directions
Authors: Makina Hela , Letaifa Asma Ben , Rachedi Abderrezak 
Published: October 2023

AbstractThe integration of Internet of Things (IoT) technology into electronic health (eHealth) applications has revolutionized the healthcare landscape, enabling real‐time patient monitoring, personalized care, and improved patient outcomes. However, this convergence of IoT and healthcare also introduces critical security and privacy challenges, needing careful consideration. This survey comprehensively explores the multifaceted realm of security and privacy issues in IoT‐based eHealth applications. First, we taxonomize the diverse security threats that arise due to the interconnected nature of IoT medical devices. Additionally, we highlight privacy concerns stemming from the collection and sharing of personal health information, while reconciling them with the need for accessible and collaborative healthcare ecosystems. Second, we synthesize functional, ethical, and regulatory perspectives to pick up the major requirements needed in the context of eHealth data during their whole lifecycle, from creation to destruction. Third, we identify emerging research strategies employed to address security and privacy concerns, such as cloud‐based solutions, decentralized technologies such as blockchain technology and InterPlanetary File System (IPFS), cryptographic approaches, fine‐grained access control strategies, and so forth. Additionally, we examine the impact of these approaches on computational efficiency, latency, and energy consumption, critically evaluating their suitability in the healthcare context. Building upon this comprehensive assessment, we outline potential future research directions aimed at advancing security and privacy measures in IoT‐based eHealth applications.