bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of Co‐Seismic Deformation of the Slow‐Moving La Sorbella Landslide in Italy Revealed by MPM Analysis
Authors: Kohler Marc , Puzrin Alexander M. 
Published: June 2022

AbstractPredicting the seismic behavior of slow‐moving landslides presents a significant challenge. Their yearly displacements of a few millimeters to several meters indicate that even before any earthquake they are balancing at the verge of instability. It is therefore not surprising that conventional analysis predicts large co‐seismic displacements even for light‐to‐moderate ground motions. In reality, however, negligibly small displacements have often been observed for such earthquakes, while strong ground motions can still lead to catastrophic failure. This discrepancy challenges both our understanding of the underlying mechanisms and the reliability of conventional analysis, resulting in significant uncertainties for risk assessment. Progress in this field has been further hindered by incompleteness of the available monitoring data and a lack of reliable numerical models capable of dealing simultaneously with small and large deformations under seismic loading. In this article, recently published monitoring data on La Sorbella landslide in Italy and the latest developments in seismic material point method analysis are used to gain insights into the mechanisms controlling the co‐seismic behavior of slow‐moving landslides. This forms the basis for a subsequent investigation of the potential landslide behavior during strong motions, using various material models. The study demonstrates that the co‐seismic behavior of La Sorbella slide is strongly influenced by the interplay between geometrical and viscous effects, as well as potential softening in the shear zone and the surrounding soil mass. The proposed approach paves a way toward quantification of these effects in risk assessment for slow‐moving landslides.
BCAT1 promotes osteoclast maturation by regulating branched-chain amino acid metabolism
Authors: Go Miyeon , Shin Eunji , Jang Seo Young , Nam Miso , Hwang Geum-Sook , Lee Soo Young 
Published: June 2022

AbstractBranched-chain aminotransferase 1 (BCAT1) transfers the amine group on branched-chain amino acids (BCAAs) to alpha-ketoglutarate. This generates glutamate along with alpha-keto acids that are eventually oxidized to provide the cell with energy. BCAT1 thus plays a critical role in sustaining BCAA concentrations and availability as an energy source. Osteoclasts have high metabolic needs during differentiation. When we assessed the levels of amino acids in bone marrow macrophages (BMMs) that were undergoing receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation, we found that the BCAA levels steadily increase during this process. In vitro analyses then showed that all three BCAAs but especially valine were needed for osteoclast maturation. Moreover, selective inhibition of BCAT1 with gabapentin significantly reduced osteoclast maturation. Expression of enzymatically dead BCAT1 also abrogated osteoclast maturation. Importantly, gabapentin inhibited lipopolysaccharide (LPS)-induced bone loss of calvaria in mice. These findings suggest that BCAT1 could serve as a therapeutic target that dampens osteoclast formation.
IDO1 plays a tumor-promoting role via MDM2-mediated suppression of the p53 pathway in diffuse large B-cell lymphoma
Authors: Sun Chengtao , Li Mengzhen , Zhang Lian , Sun Feifei , Chen Huimou , Xu Yanjie , Lan Yingxia , Zhang Li , Lu Suying , Zhu Jia , Huang Junting , Wang Juan , Hu Yang , Feng Yanfen , Zhang Yizhuo 
Published: June 2022

AbstractWith the intensive therapeutic strategies, diffuse large B-cell lymphoma (DLBCL) is still a fatal disease due to its progressive characteristics. Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator that catalyzes the commitment step of the kynurenine pathway in the immune system, its aberrant activation may contribute to malignant cell escape eradication. However, the role of IDO1 in DLBCL progression remains elusive. Our study showed IDO1 expression was upregulated in DLBCL and was associated with a poor prognosis and low overall survival. Inhibition of IDO1 suppressed DLBCL cell proliferation in vitro and impeded xenograft tumorigenesis in vivo. RNA-seq analyses revealed MDM2 was downregulated while TP53 was upregulated in IDO1 inhibition OCI-Ly10 cells. Mechanistically, IDO1 inhibition decreased the expression of MDM2, a major negative regulator of p53, and restored p53 expression in OCI-Ly3 and OCI-Ly10 cells, resulting in cell cycle arrest and apoptosis. IDO1 inhibition induced cell apoptosis coupled with PUMA and BAX upregulation, as well as BCL2 and BCL-XL downregulation. In addition, p21, a p53 transcriptional target, was upregulated in cell cycle arrest. Taken together, this study revealed IDO1 is essential for the proliferation of DLBCL cells and may be a potential therapeutic target for the treatment of DLBCL.
miR-15a and miR-20b sensitize hepatocellular carcinoma cells to sorafenib through repressing CDC37L1 and consequent PPIA downregulation
Authors: Li Li , Yu Shijun , Chen Jingde , Quan Ming , Gao Yong , Li Yandong 
Published: June 2022

AbstractSorafenib is a classical targeted drug for the treatment of advanced hepatocellular carcinoma (HCC), but intrinsic resistance severely limited its therapeutic effects. In the present study, we aimed to identify crucial genes in HCC cells that affect sorafenib resistance by a CRISPR/Cas9 genome-scale screening. The results indicated that the deficiency of miR-15a and miR-20b contributed to sorafenib resistance, whereas exogenous expression of miR-15a and miR-20b enhanced sorafenib sensitivity of HCC cells by cell viability, colony formation, and flow cytometry analyses. Further analyses revealed that cell division cycle 37 like 1 (CDC37L1) as a common target of miR-15a and 20b, was negatively regulated by the two miRNAs and could enhance sorafenib resistance of HCC cells in vitro and in vivo. Mechanistically, CDC37L1, as a cochaperone, effectively increased the expression of peptidylprolyl isomerase A (PPIA) through strengthening the binding between heat shock protein 90 (HSP90) and PPIA. The results from immunohistochemical staining of a HCC tissue microarray revealed a positive association between CDC37L1 and PPIA expression, and high expression of CDC37L1 and PPIA predicted worse prognosis of HCC patients after sorafenib therapy. Taken together, our findings reveal crucial roles of miR-15a, miR-20b, CDC37L1, and PPIA in sorafenib response of HCC cells. These factors may serve as therapeutic targets and predict prognosis for HCC treated with sorafenib.
21st-century stagnation in unvegetated sand-sea activity
Authors: Gunn Andrew , East Amy , Jerolmack Douglas J. 
Published: June 2022

AbstractSand seas are vast expanses of Earth’s surface containing large areas of aeolian dunes—topographic patterns manifest from above-threshold winds and a supply of loose sand. Predictions of the role of future climate change for sand-sea activity are sparse and contradictory. Here we examine the impact of climate on all of Earth’s presently-unvegetated sand seas, using ensemble runs of an Earth System Model for historical and future Shared Socioeconomic Pathway (SSP) scenarios. We find that almost all of the sand seas decrease in activity relative to present-day and industrial-onset for all future SSP scenarios, largely due to more intermittent sand-transport events. An increase in event wait-times and decrease in sand transport is conducive to vegetation growth. We expect dune-forming winds will become more unimodal, and produce larger incipient wavelengths, due to weaker and more seasonal winds. Our results indicate that these qualitative changes in Earth’s deserts cannot be mitigated.
POLYRETINA restores light responses in vivo in blind Göttingen minipigs
Authors: Vagni Paola , Airaghi Leccardi Marta Jole Ildelfonsa , Vila Charles-Henri , Zollinger Elodie Geneviève , Sherafatipour Golnaz , Wolfensberger Thomas J. , Ghezzi Diego 
Published: June 2022

AbstractRetinal prostheses hold the potential for artificial vision in blind people affected by incurable diseases of the outer retinal layer. Available technologies provide only a small field of view: a significant limitation for totally blind people. To overcome this problem, we recently proposed a large and high-density photovoltaic epiretinal device, known as POLYRETINA. Here, we report the in vivo assessment of POLYRETINA. First, we characterise a model of chemically-induced blindness in Göttingen minipigs. Then, we develop and test a minimally invasive injection procedure to insert the large epiretinal implant into the eye. Last, we show that POLYRETINA restores light-evoked cortical responses in blind animals at safe irradiance levels. These results indicate that POLYRETINA holds the potential for artificial vision in totally blind patients affected by retinitis pigmentosa.
Sustainable wood electronics by iron-catalyzed laser-induced graphitization for large-scale applications
Authors: Dreimol Christopher H. , Guo Huizhang , Ritter Maximilian , Keplinger Tobias , Ding Yong , Günther Roman , Poloni Erik , Burgert Ingo , Panzarasa Guido 
Published: June 2022

AbstractEcologically friendly wood electronics will help alleviating the shortcomings of state-of-art cellulose-based “green electronics”. Here we introduce iron-catalyzed laser-induced graphitization (IC-LIG) as an innovative approach for engraving large-scale electrically conductive structures on wood with very high quality and efficiency, overcoming the limitations of conventional LIG including high ablation, thermal damages, need for multiple lasing steps, use of fire retardants and inert atmospheres. An aqueous bio-based coating, inspired by historical iron-gall ink, protects wood from laser ablation and thermal damage while promoting efficient graphitization and smoothening substrate irregularities. Large-scale (100 cm2), highly conductive (≥2500 S m−1) and homogeneous surface areas are engraved single-step in ambient atmosphere with a conventional CO2 laser, even on very thin (∼450 µm) wood veneers. We demonstrate the validity of our approach by turning wood into highly durable strain sensors, flexible electrodes, capacitive touch panels and an electroluminescent LIG-based device.
Frequency and mechanisms of LINE-1 retrotransposon insertions at CRISPR/Cas9 sites
Authors: Tao Jianli , Wang Qi , Mendez-Dorantes Carlos , Burns Kathleen H. , Chiarle Roberto 
Published: June 2022

AbstractCRISPR/Cas9-based genome editing has revolutionized experimental molecular biology and entered the clinical world for targeted gene therapy. Identifying DNA modifications occurring at CRISPR/Cas9 target sites is critical to determine efficiency and safety of editing tools. Here we show that insertions of LINE-1 (L1) retrotransposons can occur frequently at CRISPR/Cas9 editing sites. Together with PolyA-seq and an improved amplicon sequencing, we characterize more than 2500 de novo L1 insertions at multiple CRISPR/Cas9 editing sites in HEK293T, HeLa and U2OS cells. These L1 retrotransposition events exploit CRISPR/Cas9-induced DSB formation and require L1 RT activity. Importantly, de novo L1 insertions are rare during genome editing by prime editors (PE), cytidine or adenine base editors (CBE or ABE), consistent with their reduced DSB formation. These data demonstrate that insertions of retrotransposons might be a potential outcome of CRISPR/Cas9 genome editing and provide further evidence on the safety of different CRISPR-based editing tools.
Shape-assisted self-assembly
Authors: Woods Joseph F. , Gallego Lucía , Pfister Pauline , Maaloum Mounir , Vargas Jentzsch Andreas , Rickhaus Michel 
Published: June 2022

AbstractSelf-assembly and molecular recognition are critical processes both in life and material sciences. They usually depend on strong, directional non-covalent interactions to gain specificity and to make long-range organization possible. Most supramolecular constructs are also at least partially governed by topography, whose role is hard to disentangle. This makes it nearly impossible to discern the potential of shape and motion in the creation of complexity. Here, we demonstrate that long-range order in supramolecular constructs can be assisted by the topography of the individual units even in the absence of highly directional interactions. Molecular units of remarkable simplicity self-assemble in solution to give single-molecule thin two-dimensional supramolecular polymers of defined boundaries. This dramatic example spotlights the critical function that topography can have in molecular assembly and paves the path to rationally designed systems of increasing sophistication.
Second order Zeeman interaction and ferroquadrupolar order in TmVO4
Authors: Vinograd I. , Shirer K. R. , Massat P. , Wang Z. , Kissikov T. , Garcia D. , Bachmann M. D. , Horvatić M. , Fisher I. R. , Curro N. J. 
Published: June 2022

AbstractTmVO4exhibits ferroquadrupolar order of the Tm 4f electronic orbitals at low temperatures, and is a model system for Ising nematicity. A magnetic field oriented along thec-axis constitutes a transverse effective field for the quadrupolar order parameter, continuously tuning the system to a quantum phase transition as the field is increased from zero. In contrast, in-plane magnetic fields couple to the order parameter only at second order, such that orienting along the primary axes of the quadrupole order results in an effective longitudinal field, whereas orienting at 45 degrees results in a second effective transverse field. Not only do in-plane fields engender a marked in-plane anisotropy of the critical magnetic and quadrupole fluctuations above the ferroquadrupolar ordering temperature, but in-plane transverse fields initially enhance the ferroquadrupolar order, before eventually suppressing it, an effect that we attribute to admixing of the higher crystalline electric field levels.
Energy demand reduction options for meeting national zero-emission targets in the United Kingdom
Authors: Barrett John , Pye Steve , Betts-Davies Sam , Broad Oliver , Price James , Eyre Nick , Anable Jillian , Brand Christian , Bennett George , Carr-Whitworth Rachel , Garvey Alice , Giesekam Jannik , Marsden Greg , Norman Jonathan , Oreszczyn Tadj , Ruyssevelt Paul , Scott Kate 
Published: June 2022

AbstractIn recent years, global studies have attempted to understand the contribution that energy demand reduction could make to climate mitigation efforts. Here we develop a bottom-up, whole-system framework that comprehensively estimates the potential for energy demand reduction at a country level. Replicable for other countries, our framework is applied to the case of the United Kingdom where we find that reductions in energy demand of 52% by 2050 compared with 2020 levels are possible without compromising on citizens’ quality of life. This translates to annual energy demands of 40 GJ per person, compared with the current Organisation for Economic Co-operation and Development average of 116 GJ and the global average of 55 GJ. Our findings show that energy demand reduction can reduce reliance on high-risk carbon dioxide removal technologies, has moderate investment requirements and allows space for ratcheting up climate ambition. We conclude that national climate policy should increasingly develop and integrate energy demand reduction measures.
Extended infusion of piperacillin–tazobactam versus intermittent infusion in critically ill egyptian patients: a cost-effectiveness study
Authors: Naiim Christina Medhat , Elmazar M. M. , Sabri Nagwa A. , Bazan Naglaa S. 
Published: June 2022

AbstractExtended infusion of piperacillin/tazobactam over 4 h has been proposed as an alternate mode of administration to the 30-min intermittent infusion to optimize treatment effects in patients with gram-negative bacterial infections. The study aimed to evaluate the extended infusion regimen of piperacillin/tazobactam in standings of efficacy, safety, and cost to the intermittent one in the treatment of gram-negative bacterial infections. A prospective randomized comparative study was performed on 53 patients, 27 in the intermittent infusion group and 26 in the extended infusion group. The primary outcome was the mean number of days to clinical success and the percentage of patients who were clinically cured after treatment. The secondary outcomes included mortality, readmission within 30-days, and cost-effectiveness analysis based on the mean number of days to clinical success. The clinical success rate was comparable in the two groups. Days on extended infusion were significantly lower than intermittent infusion (5.7 vs 8.9 days, respectively, p = 0.0001) as well as days to clinical success (4.6 vs 8.5 days, respectively, p = 0.026). The extended infusion was superior to the intermittent infusion regarding cost-effectiveness ratio ($1835.41 and $1914.09/expected success, respectively). The more cost-effective regimen was the extended infusion. Both regimens had comparable clinical and microbiological outcomes.
Embodiment of supernumerary robotic limbs in virtual reality
Authors: Arai Ken , Saito Hiroto , Fukuoka Masaaki , Ueda Sachiyo , Sugimoto Maki , Kitazaki Michiteru , Inami Masahiko 
Published: June 2022

AbstractThe supernumerary robotic limb system expands the motor function of human users by adding extra artificially designed limbs. It is important for us to embody the system as if it is a part of one’s own body and to maintain cognitive transparency in which the cognitive load is suppressed. Embodiment studies have been conducted with an expansion of bodily functions through a “substitution” and “extension”. However, there have been few studies on the “addition” of supernumerary body parts. In this study, we developed a supernumerary robotic limb system that operates in a virtual environment, and then evaluated whether the extra limb can be regarded as a part of one’s own body using a questionnaire and whether the perception of peripersonal space changes with a visuotactile crossmodal congruency task. We found that the participants can embody the extra-limbs after using the supernumerary robotic limb system. We also found a positive correlation between the perceptual change in the crossmodal congruency task and the subjective feeling that the number of one’s arms had increased (supernumerary limb sensation). These results suggest that the addition of an extra body part may cause the participants to feel that they had acquired a new body part that differs from their original body part through a functional expansion.
In silico analysis of the human milk oligosaccharide glycome reveals key enzymes of their biosynthesis
Authors: McDonald Andrew G. , Mariethoz Julien , Davey Gavin P. , Lisacek Frédérique 
Published: June 2022

AbstractHuman milk oligosaccharides (HMOs) form the third most abundant component of human milk and are known to convey several benefits to the neonate, including protection from viral and bacterial pathogens, training of the immune system, and influencing the gut microbiome. As HMO production during lactation is driven by enzymes that are common to other glycosylation processes, we adapted a model of mucin-type GalNAc-linked glycosylation enzymes to act on free lactose. We identified a subset of 11 enzyme activities that can account for 206 of 226 distinct HMOs isolated from human milk and constructed a biosynthetic reaction network that identifies 5 new core HMO structures. A comparison of monosaccharide compositions demonstrated that the model was able to discriminate between two possible groups of intermediates between major subnetworks, and to assign possible structures to several previously uncharacterised HMOs. The effect of enzyme knockouts is presented, identifying β-1,4-galactosyltransferase and β-1,3-N-acetylglucosaminyltransferase as key enzyme activities involved in the generation of the observed HMO glycosylation patterns. The model also provides a synthesis chassis for the most common HMOs found in lactating mothers.
The SKBR3 cell-membrane proteome reveals telltales of aberrant cancer cell proliferation and targets for precision medicine applications
Authors: Karcini Arba , Lazar Iulia M. 
Published: June 2022

AbstractThe plasma membrane proteome resides at the interface between the extra- and intra-cellular environment and through its various roles in signal transduction, immune recognition, nutrient transport, and cell–cell/cell–matrix interactions plays an absolutely critical role in determining the fate of a cell. Our work was aimed at exploring the cell-membrane proteome of a HER2+ breast-cancer cell line (SKBR3) to identify triggers responsible for uncontrolled cell proliferation and intrinsic resources that enable detection and therapeutic interventions. To mimic environmental conditions that enable cancer cells to evolve adaptation/survival traits, cell culture was performed under serum-rich and serum-deprived conditions. Proteomic analysis enabled the identification of ~ 2000 cell-membrane proteins. Classification into proteins with receptor/enzymatic activity, CD antigens, transporters, and cell adhesion/junction proteins uncovered overlapping roles in processes that drive cell growth, apoptosis, differentiation, immune response, adhesion and migration, as well as alternate pathways for proliferation. The large number of tumor markers (> 50) and putative drug targets (> 100) exposed a vast potential for yet unexplored detection and targeting opportunities, whereas the presence of 15 antigen immunological markers enabled an assessment of epithelial, mesenchymal or stemness characteristics. Serum-starved cells displayed altered processes related to mitochondrial OXPHOS/ATP synthesis, protein folding and localization, while serum-treated cells exhibited attributes that support tissue invasion and metastasis. Altogether, our findings advance the understanding of the biological triggers that sustain aberrant cancer cell proliferation, survival and development of resistance to therapeutic drugs, and reveal vast innate opportunities for guiding immunological profiling and precision medicine applications aimed at target selection or drug discovery.
Smartphone-based photogrammetry provides improved localization and registration of scalp-mounted neuroimaging sensors
Authors: Mazzonetto Ilaria , Castellaro Marco , Cooper Robert J. , Brigadoi Sabrina 
Published: June 2022

AbstractFunctional near infrared spectroscopy and electroencephalography are non-invasive techniques that rely on sensors placed over the scalp. The spatial localization of the measured brain activity requires the precise individuation of sensor positions and, when individual anatomical information is not available, the accurate registration of these sensor positions to a head atlas. Both these issues could be successfully addressed using a photogrammetry-based method. In this study we demonstrate that sensor positions can be accurately detected from a video recorded with a smartphone, with a median localization error of 0.7 mm, comparable if not lower, to that of conventional approaches. Furthermore, we demonstrate that the additional information of the shape of the participant’s head can be further exploited to improve the registration of the sensor’s positions to a head atlas, reducing the median sensor localization error of 31% compared to the standard registration approach.