bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital twin simulation modeling process with system dynamics: An application to naval ship operation
Authors: Choi Jinwoo , Moon Seongam , Min Soonhong 
Published: July 2023

AbstractDigital twin (DT) has been around for many years, but there is no widely accepted standardized tool or method. In this study, system dynamics was proposed as a tool that can be integrated into multi‐scale, multi‐physics, and multi‐disciplinary, which are continuously becoming issues in the DT field. Various heterogeneous data from multiple protocols or platforms could be integrated into one model. Through the five‐step model building process, it was possible to integrate the theories and various models studied in the past. In this study, the operation and maintenance system of ROK Naval ships is implemented as a proposed method. Various physics, scales, and disciplines such as failures of ships, maintenance ability of repair shops, and schedule pressure of mechanics were reflected. It was possible to observe non‐intuitive correlations and potential problems caused by the latent effect of the high‐fidelity DT model. The proposed method is also capable of updating through continuous data calibration or real‐time interworking with external statistical analysis tools.
Folgen der COVID-19-Pandemie: Gibt es Risikogruppen für ein verringertes subjektives Wohlbefinden nach dem ersten Lockdown?
Authors: Finne Emily , Razum Oliver 
Published: July 2023

Zusammenfassung
Hintergrund
Maßnahmen zur Eindämmung von COVID-19 führten zu Belastungen, die gesundheitliche Ungleichheiten verstärkt haben. Wir untersuchen, inwiefern sich Risikogruppen für ein reduziertes subjektives Wohlbefinden nach Eintreten des Lockdowns 2020 identifizieren lassen. Dabei berücksichtigen wir im Rahmen eines intersektionalen Ansatzes auch mögliche Wechselwirkungen verschiedener sozialer Gruppierungsmerkmale.

Methode
Analysiert wurden Daten des Sozio-oekonomischen Panels (SOEP) aus den Jahren 2018–2020. Insgesamt 16.000 Fälle mit Angaben zu Wohlbefindensänderungen (SF-12-Scores sowie Einzelindikatoren) wurden in die Auswertung einbezogen. Zur Identifikation von Gruppen mit unterschiedlicher Entwicklung im Wohlbefinden verwenden wir das Klassifikationsverfahren Random Forests. Zur inhaltlichen Interpretation stellen wir ergänzend Ergebnisse aus einem Regressionsmodell mit sozialen und gesundheitlichen Aspekten als Prädiktoren dar.

Ergebnisse
Demografische und soziale Merkmale erklärten nur einen sehr geringen Teil der Veränderungen im subjektiven Wohlbefinden (R2 = 0,007–0,012) und ließen keine Abgrenzung homogener Risikogruppen zu. Obwohl einige signifikante Prädiktoren in den Regressionsmodellen gefunden wurden, waren entsprechende Effekte überwiegend gering. Neben dem Ausgangszustand im Wohlbefinden vor Pandemiebeginn trugen v. a. das Vorliegen chronischer Erkrankungen und Behinderungen zur Erklärung des Wohlbefindens bei.

Diskussion
Die aktuell vorliegenden Daten ermöglichen keine klare Identifikation von Risikogruppen für Einbußen im Wohlbefinden im ersten Jahr der COVID-19-Pandemie. Der Gesundheitszustand vor Pandemiebeginn scheint für kurzfristige Veränderungen im subjektiven Wohlbefinden bedeutsamer zu sein als soziodemografische und -ökonomische Kategorisierungsmerkmale.
Improving Network Delay Predictions Using GNNs
Authors: Farreras Miquel , Soto Paola , Camelo Miguel , Fàbrega Lluís , Vilà Pere 
Published: July 2023

AbstractAutonomous network management is crucial for Fifth Generation (5G) and Beyond 5G (B5G) networks, where a constantly changing environment is expected and network configuration must adapt accordingly. Modeling tools are required to predict the impact on performance (packet and delay loss) when new traffic demands arrives and when changes in routing paths are applied in the network. Mathematical analysis and network simulators are techniques for modeling networks but both have limitations, as the former provides low accuracy and the latter requires high execution times. To overcome these limitations, machine learning (ML) algorithms, and more specifically, graph neural networks (GNNs), are proposed for network modeling due to their ability to capture complex relationships from graph-like data while predicting network properties with high accuracy and low computational requirements. However, one of the main issues when using GNNs is their lack of generalization capability to larger networks, i.e., when trained in small networks (in number of nodes, paths length, links capacity), the accuracy of predictions on larger networks is poor. This paper addresses the GNN generalization problem by the use of fundamental networking concepts. Our solution is built from a baseline GNN model called RouteNet (developed by Barcelona Neural Networking Center-Universitat Politècnica de Catalunya (BNN-UPC)) that predicts the average delay in network paths, and through a number of simple additions significantly improves the prediction accuracy in larger networks. The improvement ratio compared to the baseline model is 101, from a 187.28% to a 1.828%, measured by the Mean Average Percentage Error (MAPE). In addition, we propose a closed-loop control context where the resulting GNN model could be potentially used in different use cases.
First LIPA Mutational Analysis in Egyptian Patients Reveals One Novel Variant: Wolman Disease
Authors: Elaraby Nesma M. , Galal Eman Reda , Abdel-Hamid Mohamed , Elbendary Hasnaa M. , Elbadry Mohamed , Mekkawy Mona K. , Ashaat Neveen A. , Mounir Samir M. , Ashaat Engy A. 
Published: July 2023

AbstractLysosomal acid lipase (LAL) is a necessary enzyme for the hydrolysis of both triglycerides (TGs) and cholesteryl esters (CEs) in the lysosome. Deficiency of this enzyme encoded by the lipase A (LIPA) gene leads to LAL deficiency (LAL-D). A severe disease subtype of LAL-D is known as Wolman disease (WD), present with diarrhea, hepatosplenomegaly, and adrenal calcification. Untreated patients do not survive more than a year. The aim of this study was to assess the clinical and molecular characterizations of WD patients in Egypt. A total of seven patients (from five unrelated Egyptian families) were screened by targeted next-generation sequencing (NGS), and the co-segregation of causative variants was analyzed using Sanger sequencing. Furthermore, multiple in silico analyses were performed to assess the pathogenicity of the candidate variants. Overall, we identified three diseases causing variants harbored in the LIPA gene. One of these variants is a novel missense variant (NM_000235.4: c.1122 T > G; p. His374Gln), which was classified as a likely pathogenic variant. All variants were predicted to be disease causing using in silico analyses. Our findings expand the spectrum of variants involved in WD which may help to investigate phenotype-genotype correlation and assist genetic counseling. To the best of our knowledge, this is the first clinico-genetic study carried out on Egyptian patients affected with WD.
The impact of water table fluctuation and salinity on LNAPL distribution and geochemical properties in the smear zone under completely anaerobic conditions
Authors: Ismail Reem Elfatih , Al-Raoush Riyadh I. , Alazaiza Motasem Y. D. 
Published: July 2023

AbstractClimate and groundwater are always in a state of dynamic equilibrium. Subsurface systems contaminated by light non-aqueous phase liquid (LNAPL) present a challenge to understand the overall impact of water table dynamics, due to various interacting mechanisms, including volatilization, and LNAPL mobilization/dissolution along the groundwater flow direction and oscillating redox conditions. We investigated the impact of water table fluctuations on LNAPL natural attenuation and soil geochemical characteristics in semi-arid coastal areas under saline conditions. Four soil columns operated for 151 days under anoxic conditions where a layer of benzene and toluene were subjected to a stable and fluctuating water table associated with low and high salinity conditions. The bottom of stable and fluctuating columns reached an anaerobic state after 40 days, while the middle of stable column took 60 days. pH values of the fluctuating columns covered a wide range, and at the end shifted towards alkaline conditions, unlike the stable columns. In fluctuating columns, pore water sulfate decreased in the middle, but in stable columns, it decreased in the first 40 days, which suggested that sulfate was the primary electron donor and sulfate-reducing bacteria were present. At the source zone, benzene and toluene reached their maximum concentration after 30 and 10 days for the stable and the fluctuating columns, respectively. Significant decrease in benzene and toluene concentrations occurred under the fluctuating water table. Salinity did not affect benzene and toluene concentrations in the aqueous phase, although water table fluctuations have the most effect. Soil solid-phase analysis shows fluctuating columns have less toluene than stable columns. Solid-phase analysis showed the fluctuating columns have less benzene and toluene concentrations as compared to the stable columns.
An experimental study on aging effects of the air–fuel ratio swing on modern gasoline three-way catalysts
Authors: Eickenhorst René , Koch Thomas 
Published: July 2023

AbstractToday’s governmental legislations require region specific emission standards for passenger vehicles. Continuously increasing legal requirements demand the development of more complex exhaust gas after treatment systems to further reduce harmful gases like carbon monoxide (CO), hydrocarbons (HC) and nitrogen oxides (NOx). Due to specific load profiles and other boundary conditions, the efficiency of the aftertreatment system declines over lifecycle, so that the emissions might increase. Consequently, the durability of the system becomes a critical design parameter with upcoming legislation demanding emissions stability over the vehicle life cycle. Within this publication, catalyst aging effects due to air–fuel ratio (AFR) swing are analyzed experimentally. To create catalyst aging conditions, a modern eight-cylinder turbocharged engine was modified and specific aging cycles with a variation of AFR swing amplitude and frequency were conducted. Light-off curves were used to depict the negative impact of the AFR swing on the aging catalyst systems. A higher swing frequency resulted in an increased temperature amplitude within the entrance area of the catalyst, while an elevated amplitude lead to more exothermic heat release and stronger aging over the complete catalyst, as visualized via conversion maps. A theoretical calculation of thermal loads by Arrhenius equation supports the results and indicates the direction of supplementary experimental approaches.
Montmorillonite as an Anti-Tuberculosis Rifampicin Drug Carrier: DFT and Experimental Study
Authors: Scholtzová Eva , Jankovič Luboš , Tunega Daniel 
Published: July 2023

AbstractA hybrid of montmorillonite (Mnt) and rifampicin (RIF) was synthesized and the structure and stability of the drug carrier system clarified. Density functional theory calculations involving dispersion corrections (DFT-D3) were performed to characterize interactions acting in the interlayer space of montmorillonite intercalated with rifampicin. The structure and stability of the RIF-Mnt intercalated complex were determined. Calculations revealed the deformation of the molecular structure of rifampicin after intercalation into the Mnt interlayer space due to the clay environment. The ansa chain of RIF was bent in the interlayer space compared with the structure of the RIF molecule in the monocrystal. RIF was keyed into the Mnt surface by means of numerous hydrogen bonds of weak to moderate strength. The calculated vibrational spectrum from ab initio molecular dynamics (AIMD) was in good agreement with the FTIR measured spectra and helped to analyze the overlapped vibrational bands. Based on analysis of structural stability, theoretical calculations revealed that Mnt is a suitable drug carrier for delayed release of the RIF drug. Batch adsorption experiments showed the large adsorption capacity of montmorillonite for RIF.
New Constraints on the Late Oligocene‐Miocene Thermo‐Tectonic Evolution of the Southeastern Tibetan Plateau From Low‐Temperature Thermochronology
Authors: He Zhiyuan , Zhong Linglin , Cao Kai , Su Wenbo , Glorie Stijn , Zhong Kanghui , Sun Chuang , De Grave Johan 
Published: July 2023

AbstractThe southeastern (SE) Tibetan Plateau (Yunnan) is characterized by low‐relief uplands that were deeply incised by large rivers. The thermal history of basement rocks in this region remains poorly investigated, while this data is needed to elucidate the complex relationship between tectonics and climate in shaping the surface. To better understand its thermo‐tectonic evolution, we carried out apatite fission track thermochronology on 31 samples collected from a large area that covers different tectonic units, including a vertical profile in the middle Mekong River valley; additional zircon LA‐ICP‐MS U‐Pb dating was performed on four basement rocks. Our results confirm that a large portion of Mesozoic crystalline rocks constitute the basement of the SE Tibetan Plateau. Inverse thermal history modeling of fission track data reveal extensive late Oligocene to Miocene rapid basement cooling and exhumation episodes from both inside and outside the active zones (i.e., ductile shear zone and river valley). These thermal events were coincident with the activities of large‐scale strike‐slip faults that dominate the structural framework. Combined with the published data, we propose that widespread crustal shortening and thickening took place in the SE Tibetan Plateau during the Oligocene‐Miocene in the context of a compressive tectonic regime. Low‐temperature thermochronological data reveal that both tectonic forcing and climate‐driven erosion have played important roles in exhuming the basement rocks in the region. It is also deduced that the present‐day relatively low‐elevation landscape of the Yunnan area resulted from complex interaction between regional tectonic activity and surficial erosion since the late Oligocene.
Enhancing bacteriophage therapeutics through in situ production and release of heterologous antimicrobial effectors
Authors: Du Jiemin , Meile Susanne , Baggenstos Jasmin , Jäggi Tobias , Piffaretti Pietro , Hunold Laura , Matter Cassandra I. , Leitner Lorenz , Kessler Thomas M. , Loessner Martin J. , Kilcher Samuel , Dunne Matthew 
Published: July 2023

AbstractBacteriophages operate via pathogen-specific mechanisms of action distinct from conventional, broad-spectrum antibiotics and are emerging as promising alternative antimicrobials. However, phage-mediated killing is often limited by bacterial resistance development. Here, we engineer phages for target-specific effector gene delivery and host-dependent production of colicin-like bacteriocins and cell wall hydrolases. Using urinary tract infection (UTI) as a model, we show how heterologous effector phage therapeutics (HEPTs) suppress resistance and improve uropathogen killing by dual phage- and effector-mediated targeting. Moreover, we designed HEPTs to control polymicrobial uropathogen communities through production of effectors with cross-genus activity. Using phage-based companion diagnostics, we identified potential HEPT responder patients and treated their urine ex vivo. Compared to wildtype phage, a colicin E7-producing HEPT demonstrated superior control of patient E. coli bacteriuria. Arming phages with heterologous effectors paves the way for successful UTI treatment and represents a versatile tool to enhance and adapt phage-based precision antimicrobials.
Involvement of skin TRPV3 in temperature detection regulated by TMEM79 in mice
Authors: Lei Jing , Yoshimoto Reiko U. , Matsui Takeshi , Amagai Masayuki , Kido Mizuho A. , Tominaga Makoto 
Published: July 2023

AbstractTRPV3, a non-selective cation transient receptor potential (TRP) ion channel, is activated by warm temperatures. It is predominantly expressed in skin keratinocytes, and participates in various somatic processes. Previous studies have reported that thermosensation in mice lacking TRPV3 was impaired. Here, we identified a transmembrane protein, TMEM79, that acts as a negative regulator of TRPV3. Heterologous expression of TMEM79 was capable of suppressing TRPV3-mediated currents in HEK293T cells. In addition, TMEM79 modulated TRPV3 translocalization and promoted its degradation in the lysosomes. TRPV3-mediated currents and Ca2+ influx were potentiated in primary mouse keratinocytes lacking TMEM79. Furthermore, TMEM79-deficient male mice preferred a higher temperature than did wild-type mice due to elevated TRPV3 function. Our study revealed unique interactions between TRPV3 and TMEM79, both in vitro and in vivo. These findings support roles for TMEM79 and TRPV3 in thermosensation.
Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment
Authors: Haake Markus , Haack Beatrice , Schäfer Tina , Harter Patrick N. , Mattavelli Greta , Eiring Patrick , Vashist Neha , Wedekink Florian , Genssler Sabrina , Fischer Birgitt , Dahlhoff Julia , Mokhtari Fatemeh , Kuzkina Anastasia , Welters Marij J. P. , Benz Tamara M. , Sorger Lena , Thiemann Vincent , Almanzar Giovanni , Selle Martina , Thein Klara , Späth Jacob , Gonzalez Maria Cecilia , Reitinger Carmen , Ipsen-Escobedo Andrea , Wistuba-Hamprecht Kilian , Eichler Kristin , Filipski Katharina , Zeiner Pia S. , Beschorner Rudi , Goedemans Renske , Gogolla Falk Hagen , Hackl Hubert , Rooswinkel Rogier W. , Thiem Alexander , Roche Paula Romer , Joshi Hemant , Pühringer Dirk , Wöckel Achim , Diessner Joachim E. , Rüdiger Manfred , Leo Eugen , Cheng Phil F. , Levesque Mitchell P. , Goebeler Matthias , Sauer Markus , Nimmerjahn Falk , Schuberth-Wagner Christine , von Felten Stefanie , Mittelbronn Michel , Mehling Matthias , Beilhack Andreas , van der Burg Sjoerd H. , Riedel Angela , Weide Benjamin , Dummer Reinhard , Wischhusen Jörg 
Published: July 2023

AbstractImmune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.
Identification of a small-molecule inhibitor that selectively blocks DNA-binding by Trypanosoma brucei replication protein A1
Authors: Mukherjee Aditi , Hossain Zakir , Erben Esteban , Ma Shuai , Choi Jun Yong , Kim Hee-Sook 
Published: July 2023

AbstractReplication Protein A (RPA) is a broadly conserved complex comprised of the RPA1, 2 and 3 subunits. RPA protects the exposed single-stranded DNA (ssDNA) during DNA replication and repair. Using structural modeling, we discover an inhibitor, JC-229, that targets RPA1 in Trypanosoma brucei, the causative parasite of African trypanosomiasis. The inhibitor is highly toxic to T. brucei cells, while mildly toxic to human cells. JC-229 treatment mimics the effects of TbRPA1 depletion, including DNA replication inhibition and DNA damage accumulation. In-vitro ssDNA-binding assays demonstrate that JC-229 inhibits the activity of TbRPA1, but not the human ortholog. Indeed, despite the high sequence identity with T. cruzi and Leishmania RPA1, JC-229 only impacts the ssDNA-binding activity of TbRPA1. Site-directed mutagenesis confirms that the DNA-Binding Domain A (DBD-A) in TbRPA1 contains a JC-229 binding pocket. Residue Serine 105 determines specific binding and inhibition of TbRPA1 but not T. cruzi and Leishmania RPA1. Our data suggest a path toward developing and testing highly specific inhibitors for the treatment of African trypanosomiasis.
Herbarium specimen sequencing allows precise dating of Xanthomonas citri pv. citri diversification history
Authors: Campos Paola E. , Pruvost Olivier , Boyer Karine , Chiroleu Frederic , Cao Thuy Trang , Gaudeul Myriam , Baider Cláudia , Utteridge Timothy M. A. , Becker Nathalie , Rieux Adrien , Gagnevin Lionel 
Published: July 2023

AbstractHerbarium collections are an important source of dated, identified and preserved DNA, whose use in comparative genomics and phylogeography can shed light on the emergence and evolutionary history of plant pathogens. Here, we reconstruct 13 historical genomes of the bacterial crop pathogen Xanthomonas citri pv. citri (Xci) from infected Citrus herbarium specimens. Following authentication based on ancient DNA damage patterns, we compare them with a large set of modern genomes to estimate their phylogenetic relationships, pathogenicity-associated gene content and several evolutionary parameters. Our results indicate that Xci originated in Southern Asia ~11,500 years ago (perhaps in relation to Neolithic climate change and the development of agriculture) and diversified during the beginning of the 13th century, after Citrus diversification and before spreading to the rest of the world (probably via human-driven expansion of citriculture through early East-West trade and colonization).
Structural basis of the T4 bacteriophage primosome assembly and primer synthesis
Authors: Feng Xiang , Spiering Michelle M. , de Luna Almeida Santos Ruda , Benkovic Stephen J. , Li Huilin 
Published: July 2023

AbstractThe T4 bacteriophage gp41 helicase and gp61 primase assemble into a primosome to couple DNA unwinding with RNA primer synthesis for DNA replication. How the primosome is assembled and how the primer length is defined are unclear. Here we report a series of cryo-EM structures of T4 primosome assembly intermediates. We show that gp41 alone is an open spiral, and ssDNA binding triggers a large-scale scissor-like conformational change that drives the ring closure and activates the helicase. Helicase activation exposes a cryptic hydrophobic surface to recruit the gp61 primase. The primase binds the helicase in a bipartite mode in which the N-terminal Zn-binding domain and the C-terminal RNA polymerase domain each contain a helicase-interacting motif that bind to separate gp41 N-terminal hairpin dimers, leading to the assembly of one primase on the helicase hexamer. Our study reveals the T4 primosome assembly process and sheds light on the RNA primer synthesis mechanism.