bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence Rates of Electromagnetic Ion Cyclotron (EMIC) Waves With Rising Tones in the Van Allen Probes Data Set
Authors: Sigsbee K. , Kletzing C. A. , Faden J. , Smith C. W.
Published: January 2023

In Fourier time‐frequency power spectrograms of satellite magnetic field data, electromagnetic ion cyclotron (EMIC) waves may feature discrete, rising tone structures that rapidly increase in frequency. Using data from the Van Allen Probes Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS) fluxgate magnetometer, we conducted a statistical study of EMIC waves from September 2012 through June 2016. We compared the occurrence rates and spatial distributions for all EMIC waves with those for rising tone EMIC waves as a function of magnetic local time (MLT) and L shell, as well as a function of RXY and Z in solar‐magnetic (SM) coordinates. Overall, EMIC waves occurred during 2.4% of the time period considered, but rising tone EMIC waves were only found during 0.2% of the time period considered. About 7%–8% of the minutes of orbital coverage with H+ or He+ band EMIC waves had rising tones. The regions of peak occurrence rates for H+ and He+ band waves, as well as waves with rising tones, were found in the noon and dusk sectors for 4 < L < 6. The preferred regions for H+ waves as a function of RXY and Z SM suggest an association with magnetospheric compressions near noon and interactions between plumes and the ring current near dusk. Peak occurrence rates for O+ band waves were found between 2 < L < 4 at all MLT, and over a wide range of L shells near dusk. No rising tones were found in the O+ band.
Intensified Mussel Farming; Impacts on Nutrient Budgets and Ecology in a Eutrophic Semi‐Enclosed Fjord System
Authors: Maar M. , Larsen J. , Schourup‐Kristensen V.
Published: January 2023

Compared to land‐based sources, mussel aquaculture provides food products with a high‐quality protein content and a low carbon footprint. At the same time, mussel cultures store nutrients in their tissue that are removed from the system through harvesting. However, increasingly development of suspended bivalve aquaculture in the coastal zone also comes with a price as the ecological carrying capacity of the ecosystem may be exceeded. The present study aims to support future fjord‐management by estimating the nutrient budgets and ecological impacts of intensified mussel aquaculture in a shallow semi‐enclosed system, the Limfjorden, using 3D ecosystem modeling. Model results showed a net removal of nutrients by suspended mussel cultures at basin scale, whereas at farm scale the efficiency was lower due to increased sediment fluxes. An increase in mussel farming from the current 4 kt‐fresh weight to a future projection of 104 kt‐fresh weight did not exceed the ecological carrying capacity with respect to impacts on sediment chemistry but could cause local declines in benthic bivalve populations. Intense mussel farming provided ecosystem services such as better oxygen conditions and higher Secchi depth together with lower nutrient‐ and chlorophyll a concentrations on basin scale. In addition, there was a redistribution of nutrients, chlorophyll a concentrations, and Secchi depth between sub‐basins in the fjord depending on farming location and intensity. Overall, intensified mussel farming could contribute to the mitigation of eutrophication effects by removing nutrients from land sources and by reducing the local sediment loading.
Comparison of phenomics and cfDNA in a large breast screening population: the Breast Screening and Monitoring Study (BSMS)
Authors: Stebbing Justin , Takis Panteleimon G. , Sands Caroline J. , Maslen Lynn , Lewis Matthew R. , Gleason Kelly , Page Karen , Guttery David , Fernandez-Garcia Daniel , Primrose Lindsay , Shaw Jacqueline A.
Published: January 2023

To assess their roles in breast cancer diagnostics, we aimed to compare plasma cell-free DNA (cfDNA) levels with the circulating metabolome in a large breast screening cohort of women recalled for mammography, including healthy women and women with mammographically detected breast diseases, ductal carcinoma in situ and invasive breast cancer: the Breast Screening and Monitoring Study (BSMS). In 999 women, plasma was analyzed by nuclear magnetic resonance (NMR) and Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) and then processed to isolate and quantify total cfDNA. NMR and UPLC-MS results were compared with data for 186 healthy women derived from the AIRWAVE cohort. Results showed no significant differences between groups for all metabolites, whereas invasive cancers had significantly higher plasma cfDNA levels than all other groups. When stratified the supervised OPLS-DA analysis and total cfDNA concentration showed high discrimination accuracy between invasive cancers and the disease/medication-free subjects. Furthermore, comparison of OPLS-DA data for invasive breast cancers with the AIRWAVE cohort showed similar discrimination between breast cancers and healthy controls. This is the first report of agreement between metabolomics and plasma cfDNA levels for discriminating breast cancer from healthy subjects in a true screening population. It also emphasizes the importance of sample standardization. Follow on studies will involve analysis of candidate features in a larger validation series as well as comparing results with serial plasma samples taken at the next routine screening mammography appointment. The findings here help establish the role of plasma analysis in the diagnosis of breast cancer in a large real-world cohort.
The pseudokinase NRBP1 activates Rac1/Cdc42 via P-Rex1 to drive oncogenic signalling in triple-negative breast cancer
Authors: Yang Xue , Cruz Miguel I. , Nguyen Elizabeth V. , Huang Cheng , Schittenhelm Ralf B. , Luu Jennii , Cowley Karla J. , Shin Sung-Young , Nguyen Lan K. , Lim Kam Sian Terry C. C. , Clark Kimberley C. , Simpson Kaylene J. , Ma Xiuquan , Daly Roger J.
Published: January 2023

We have determined that expression of the pseudokinase NRBP1 positively associates with poor prognosis in triple negative breast cancer (TNBC) and is required for efficient migration, invasion and proliferation of TNBC cells in culture as well as growth of TNBC orthotopic xenografts and experimental metastasis. Application of BioID/MS profiling identified P-Rex1, a known guanine nucleotide exchange factor for Rac1, as a NRBP1 binding partner. Importantly, NRBP1 overexpression enhanced levels of GTP-bound Rac1 and Cdc42 in a P-Rex1-dependent manner, while NRBP1 knockdown reduced their activation. In addition, NRBP1 associated with P-Rex1, Rac1 and Cdc42, suggesting a scaffolding function for this pseudokinase. NRBP1-mediated promotion of cell migration and invasion was P-Rex1-dependent, while constitutively-active Rac1 rescued the effect of NRBP1 knockdown on cell proliferation and invasion. Generation of reactive oxygen species via a NRBP1/P-Rex1 pathway was implicated in these oncogenic roles of NRBP1. Overall, these findings define a new function for NRBP1 and a novel oncogenic signalling pathway in TNBC that may be amenable to therapeutic intervention.
Neural substrates of continuous and discrete inhibitory control
Authors: Howlett Jonathon R. , Park Heekyeong , Paulus Martin P.
Published: January 2023

Inhibitory control dysfunctions play an important role in psychiatric disorders but the precise nature of these dysfunctions is still not well understood. Advances in computational modeling of real-time motor control using a proportion–integral–derivative (PID) control framework have parsed continuous motor inhibition into a preemptive drive component (signified by theKpparameter) and a reactive damping component (signified by theKdparameter). This investigation examined the relationship between inhibitory control processing during a stop signal task and continuous motor control during a simulated one-dimensional driving task in a transdiagnostic sample of participants. A transdiagnostic psychiatric sample of 492 individuals completed a stop signal task during functional magnetic resonance imaging and a simple behavioral motor control task, which was modeled using the PID framework. We examined associations between theKpandKdparameters and behavioral indices as well as neural activation on the stop signal task. Individuals with higher damping, controlling for a drive, on the driving task exhibited relatively less strategic adjustment after a stop trial (indexed by the difference in go trial reaction time and by stop trial accuracy) on the stop signal task. Individuals with higher damping, controlling for a drive, additionally exhibited increased activity in the frontal and parietal regions as well as the insula and caudate during response inhibition on the stop signal task. The results suggest that computational indices of motor control performance may serve as behavioral markers of the functioning of neural systems involved in inhibitory control.
Alterations of cohesin complex genes in acute myeloid leukemia: differential co-mutations, clinical presentation and impact on outcome
Authors: Eckardt Jan-Niklas , Stasik Sebastian , Röllig Christoph , Sauer Tim , Scholl Sebastian , Hochhaus Andreas , Crysandt Martina , Brümmendorf Tim H. , Naumann Ralph , Steffen Björn , Kunzmann Volker , Einsele Hermann , Schaich Markus , Burchert Andreas , Neubauer Andreas , Schäfer-Eckart Kerstin , Schliemann Christoph , Krause Stefan W. , Herbst Regina , Hänel Mathias , Hanoun Maher , Kaiser Ulrich , Kaufmann Martin , Rácil Zdenek , Mayer Jiri , Cerqueira Tiago , Kroschinsky Frank , Berdel Wolfgang E. , Serve Hubert , Müller-Tidow Carsten , Platzbecker Uwe , Baldus Claudia D. , Schetelig Johannes , Siepmann Timo , Bornhäuser Martin , Middeke Jan Moritz , Thiede Christian
Published: January 2023

Functional perturbations of the cohesin complex with subsequent changes in chromatin structure and replication are reported in a multitude of cancers including acute myeloid leukemia (AML). Mutations of its STAG2 subunit may predict unfavorable risk as recognized by the 2022 European Leukemia Net recommendations, but the underlying evidence is limited by small sample sizes and conflicting observations regarding clinical outcomes, as well as scarce information on other cohesion complex subunits. We retrospectively analyzed data from a multi-center cohort of 1615 intensively treated AML patients and identified distinct co-mutational patters for mutations of STAG2, which were associated with normal karyotypes (NK) and concomitant mutations in IDH2, RUNX1, BCOR, ASXL1, and SRSF2. Mutated RAD21 was associated with NK, mutated EZH2, KRAS, CBL, and NPM1. Patients harboring mutated STAG2 were older and presented with decreased white blood cell, bone marrow and peripheral blood blast counts. Overall, neither mutated STAG2, RAD21, SMC1A nor SMC3 displayed any significant, independent effect on clinical outcomes defined as complete remission, event-free, relapse-free or overall survival. However, we found almost complete mutual exclusivity of genetic alterations of individual cohesin subunits. This mutual exclusivity may be the basis for therapeutic strategies via synthetic lethality in cohesin mutated AML.
In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
Authors: Ou Wenquan , Stewart Samantha , White Alisa , Kwizera Elyahb A. , Xu Jiangsheng , Fang Yuanzhang , Shamul James G. , Xie Changqing , Nurudeen Suliat , Tirada Nikki P. , Lu Xiongbin , Tkaczuk Katherine H. R. , He Xiaoming
Published: January 2023

Cancer immunotherapy that deploys the host’s immune system to recognize and attack tumors, is a promising strategy for cancer treatment. However, its efficacy is greatly restricted by the immunosuppressive (i.e., immunologically cold) tumor microenvironment (TME). Here, we report an in-situ cryo-immune engineering (ICIE) strategy for turning the TME from immunologically “cold” into “hot”. In particular, after the ICIE treatment, the ratio of the CD8+ cytotoxic T cells to the immunosuppressive regulatory T cells is increased by more than 100 times in not only the primary tumors with cryosurgery but also distant tumors without freezing. This is achieved by combining cryosurgery that causes “frostbite” of tumor with cold-responsive nanoparticles that not only target tumor but also rapidly release both anticancer drug and PD-L1 silencing siRNA specifically into the cytosol upon cryosurgery. This ICIE treatment leads to potent immunogenic cell death, which promotes maturation of dendritic cells and activation of CD8+ cytotoxic T cells as well as memory T cells to kill not only primary but also distant/metastatic breast tumors in female mice (i.e., the abscopal effect). Collectively, ICIE may enable an efficient and durable way to leverage the immune system for combating cancer and its metastasis.
Element- and enantiomer-selective visualization of molecular motion in real-time
Authors: Mincigrucci R. , Rouxel J. R. , Rossi B. , Principi E. , Bottari C. , Catalini S. , Pelli-Cresi J. S. , Fainozzi D. , Foglia L. , Simoncig A. , Matruglio A. , Kurdi G. , Capotondi F. , Pedersoli E. , Perucchi A. , Piccirilli F. , Gessini A. , Giarola M. , Mariotto G. , Oppermann M. , Mukamel S. , Bencivenga F. , Chergui M. , Masciovecchio C.
Published: January 2023

Ultrafast optical-domain spectroscopies allow to monitor in real time the motion of nuclei in molecules. Achieving element-selectivity had to await the advent of time resolved X-ray spectroscopy, which is now commonly carried at X-ray free electron lasers. However, detecting light element that are commonly encountered in organic molecules, remained elusive due to the need to work under vacuum. Here, we present an impulsive stimulated Raman scattering (ISRS) pump/carbon K-edge absorption probe investigation, which allowed observation of the low-frequency vibrational modes involving specific selected carbon atoms in the Ibuprofen RS dimer. Remarkably, by controlling the probe light polarization we can preferentially access the enantiomer of the dimer to which the carbon atoms belong.
Structural mechanism of BRD4-NUT and p300 bipartite interaction in propagating aberrant gene transcription in chromatin in NUT carcinoma
Authors: Yu Di , Liang Yingying , Kim Claudia , Jaganathan Anbalagan , Ji Donglei , Han Xinye , Yang Xuelan , Jia Yanjie , Gu Ruirui , Wang Chunyu , Zhang Qiang , Cheung Ka Lung , Zhou Ming-Ming , Zeng Lei
Published: January 2023

BRD4-NUT, a driver fusion mutant in rare and highly aggressive NUT carcinoma, acts in aberrant transcription of anti-differentiation genes by recruiting histone acetyltransferase (HAT) p300 and promoting p300-driven histone hyperacetylation and nuclear condensation in chromatin. However, the molecular basis of how BRD4-NUT recruits and activates p300 remains elusive. Here, we report that BRD4-NUT contains two transactivation domains (TADs) in NUT that bind to the TAZ2 domain in p300. Our NMR structures reveal that NUT TADs adopt amphipathic helices when bound to the four-helical bundle TAZ2 domain. The NUT protein forms liquid-like droplets in-vitro that are enhanced by TAZ2 binding in 1:2 stoichiometry. The TAD/TAZ2 bipartite binding in BRD4-NUT/p300 triggers allosteric activation of p300 and acetylation-driven liquid-like condensation on chromatin that comprise histone H3 lysine 27 and 18 acetylation and transcription proteins BRD4L/S, CDK9, MED1, and RNA polymerase II. The BRD4-NUT/p300 chromatin condensation is key for activating transcription of pro-proliferation genes such as ALX1, resulting ALX1/Snail signaling and epithelial-to-mesenchymal transition. Our study provides a previously underappreciated structural mechanism illuminating BRD4-NUT’s bipartite p300 recruitment and activation in NUT carcinoma that nucleates a feed-forward loop for propagating histone hyperacetylation and chromatin condensation to sustain aberrant anti-differentiation gene transcription and perpetual tumor cell growth.
scMoMaT jointly performs single cell mosaic integration and multi-modal bio-marker detection
Authors: Zhang Ziqi , Sun Haoran , Mariappan Ragunathan , Chen Xi , Chen Xinyu , Jain Mika S. , Efremova Mirjana , Teichmann Sarah A. , Rajan Vaibhav , Zhang Xiuwei
Published: January 2023

Single cell data integration methods aim to integrate cells across data batches and modalities, and data integration tasks can be categorized into horizontal, vertical, diagonal, and mosaic integration, where mosaic integration is the most general and challenging case with few methods developed. We propose scMoMaT, a method that is able to integrate single cell multi-omics data under the mosaic integration scenario using matrix tri-factorization. During integration, scMoMaT is also able to uncover the cluster specific bio-markers across modalities. These multi-modal bio-markers are used to interpret and annotate the clusters to cell types. Moreover, scMoMaT can integrate cell batches with unequal cell type compositions. Applying scMoMaT to multiple real and simulated datasets demonstrated these features of scMoMaT and showed that scMoMaT has superior performance compared to existing methods. Specifically, we show that integrated cell embedding combined with learned bio-markers lead to cell type annotations of higher quality or resolution compared to their original annotations.
Toxin expression during Staphylococcus aureus infection imprints host immunity to inhibit vaccine efficacy
Authors: Teymournejad Omid , Li Zhaotao , Beesetty Pavani , Yang Ching , Montgomery Christopher P.
Published: January 2023

Staphylococcus aureus infections are a major public health issue, and a vaccine is urgently needed. Despite a considerable promise in preclinical models, all vaccines tested thus far have failed to protect humans against S. aureus. Unlike laboratory mice, humans are exposed to S. aureus throughout life. In the current study, we hypothesized that prior exposure to S. aureus “imprints” the immune response to inhibit vaccine-mediated protection. We established a mouse model in which S. aureus skin and soft tissue infection (SSTI) is followed by vaccination and secondary SSTI. Unlike naïve mice, S. aureus-sensitized mice were incompletely protected against secondary SSTI by vaccination with the inactivated α-hemolysin (Hla) mutant HlaH35L. Inhibition of protection was specific for the HlaH35L vaccine and required hla expression during primary SSTI. Surprisingly, inhibition occurred at the level of vaccine-elicited effector T cells; hla expression during primary infection limited the expansion of T cells and dendritic cells and impaired vaccine-specific T cell responses. Importantly, the T cell-stimulating adjuvant CAF01 rescued inhibition and restored vaccine-mediated protection. Together, these findings identify a potential mechanism for the failure of translation of promising S. aureus vaccines from mouse models to clinical practice and suggest a path forward to prevent these devastating infections.
Prognostic and predictive value of a lncRNA signature in patients with stage II colon cancer
Authors: Qu Ailin , Wang Qian , Chang Qing , Liu Jingkang , Yang Yongmei , Zhang Xin , Zhang Yanli , Zhang Xiaoshi , Wang Hongchun , Zhang Yi
Published: January 2023

The current staging method is inadequate to identify high-risk recurrence patients with stage II colon cancer (CC). Using a systematic and comprehensive-biomarker discovery and validation method, we aimed to construct a lncRNA-based signature to improve the prognostic prediction of stage II CC. We identified 1,377 differently expressed lncRNAs by analyzing 16 paired stage II CC tumor tissue and adjacent normal mucosal tissue from the TCGA dataset. Subsequently, using a univariable and step multivariable Cox regression model, we trained an 11-lncRNA signature in the training cohort (n = 141), which could divide patients into high-risk and low-risk groups (AUC at 3 years = 0.801, 95% CI: 0.724–0.877; AUC at 5 years = 0.801, 95% CI: 0.718–0.885). Significantly, patients in the high-risk group had poorer recurrence-free survival (RFS) compared with the low-risk group (log-rank test, P < 0.001 in the training cohort). This lncRNA-based signature was further confirmed in the validation cohort (P < 0.001). Multivariate Cox regression and stratified survival analyses showed that the prognostic value of this signature was independent of other clinicopathological risk factors (CEA, T stage, and chemotherapy). Time-dependent receiver operating characteristic (ROC) analysis demonstrated that this signature had better prognostic ability than any other clinical risk factors or single lncRNAs (all P < 0.05). A nomogram was constructed for clinical use, which integrated both the lncRNA-based signature and clinical risk factors (CEA and T stage) and performed well in the calibration plots. Altogether, our lncRNA-based signature was an independent prognostic factor and possessed a stronger predictive power compared with the currently used clinicopathological risk factors when predicting the recurrence of patients with stage II CC. Collectively, this lncRNA-based signature might facilitate individualized treatment decisions and postoperative counseling, ultimately contributing to improved survival.
Feasibility of a multigroup Boltzmann–Fokker–Planck solution for electron beam dose calculations
Authors: Naceur Ahmed , Hébert Alain , Romano Paul , Forget Benoit , Chilian Cornelia , Carrier Jean-François
Published: January 2023

Legacy nuclear-reactor Boltzmann solvers start clinical deployment as an alternative to Monte Carlo (MC) codes and Fermi–Eyges semiemprical models in radiation oncology treatment planning. Today’s certified clinical solvers are limited to photon beams. In this paper, ELECTR, a state-of-the-art multigroup electron cross sections generation module in NJOY is presented and validated against Lockwood’s calorimetric measurements, EGS-nrc and GEANT-4 for 1–20 MeV unidirectional electron beams. The nuclear-reactor DRAGON-5 solver is upgraded to access the library and solve the Boltzmann–Fokker–Planck (BFP) equation. A variety of heterogeneous radiotherapy and radiosurgery phantom configurations were used for validation purpose. Case studies include a thorax benchmark, that of a typical breast Intra-Operative Radiotherapy and a high-heterogeneity patient-like benchmark. For all beams,$$100\%$$100%of the water voxels satisfied the American Association of Physicists in Medicine accuracy criterion for a BFP-MC dose error below$$2\%$$2%. At least,$$97.0\%$$97.0%of adipose, muscle, bone, lung, tumor and breast voxels satisfied the$$2\%$$2%criterion. The average BFP-MC relative error was about$$0.56\%$$0.56%for all voxels, beams and materials combined. By irradiating homogeneous slabs from$$Z=1$$Z=1(hydrogen) to$$Z=99$$Z=99(einsteinium), we reported performance and defects of the CEPXS mode [US. Sandia National Lab., SAND-89-1685] in ELECTR for the entire periodic table. For all Lockwood’s benchmarks, NJOY-DRAGON dose predictions are within the experimental data precision for$$98\%$$98%of voxels.
Design of an artificial phage-display library based on a new scaffold improved for average stability of the randomized proteins
Authors: Gomes M. , Fleck A. , Degaugue A. , Gourmelon F. , Léger C. , Aumont-Nicaise M. , Mesneau A. , Jean-Jacques H. , Hassaine G. , Urvoas A. , Minard P. , Valerio-Lepiniec M.
Published: January 2023

Scaffold-based protein libraries are designed to be both diverse and rich in functional/folded proteins. However, introducing an extended diversity while preserving stability of the initial scaffold remains a challenge. Here we developed an original approach to select the ensemble of folded proteins from an initial library. The thermostable CheY protein from Thermotoga maritima was chosen as scaffold. Four loops of CheY were diversified to create a new binding surface. The subset of the library giving rise to folded proteins was first selected using a natural protein partner of the template scaffold. Then, a gene shuffling approach based on a single restriction enzyme was used to recombine DNA sequences encoding these filtrated variants. Taken together, the filtration strategy and the shuffling of the filtrated sequences were shown to enrich the library in folded and stable sequences while maintaining a large diversity in the final library (Lib-Cheytins 2.1). Binders of the Oplophorus luciferase Kaz domain were then selected by phage display from the final library, showing affinities in the μM range. One of the best variants induced a loss of 92% of luminescent activity, suggesting that this Cheytin preferentially binds to the Kaz active site.
Increasing beam stability zone in synchrotron light sources using polynomial quasi-invariants
Authors: Sánchez Edgar Andrés , Flores Alain , Hernández-Cobos Jorge , Moreno Matías , Antillón Armando
Published: January 2023

The objective of this article is to propose a scheme to increase the stability zone of a charged particles beam in synchrotrons using a suitable objective function that, when optimized, inhibits the resonances onset in phase space and the dynamic aperture of electrons in storage rings can be improved. The proposed technique is implemented by constructing a quasi-invariant in a neighborhood of the origin of the phase space, then, by using symbolic computation software, sets of coupled differential equations for functions involved in nonlinear dynamics are obtained and solved numerically with periodic boundary conditions. The objective function is constructed by proposing that the innermost momentum solution branch of the polynomial quasi-invariant approaches to the corresponding ellipse of the linear dynamics. The objective function is optimized using a genetic algorithm, allowing the dynamic aperture to be increased. The quality of results obtained with this scheme are compared with particle tracking simulations performed with available software in the field, showing good agreement. The scheme is applied to a synchrotron light source model that can be classified as third generation due to its emittance.
A novel neural network model of Earth’s topside ionosphere
Authors: Smirnov Artem , Shprits Yuri , Prol Fabricio , Lühr Hermann , Berrendorf Max , Zhelavskaya Irina , Xiong Chao
Published: January 2023

The Earth’s ionosphere affects the propagation of signals from the Global Navigation Satellite Systems (GNSS). Due to the non-uniform coverage of available observations and complicated dynamics of the region, developing accurate models of the ionosphere has been a long-standing challenge. Here, we present a Neural network-based model of Electron density in the Topside ionosphere (NET), which is constructed using 19 years of GNSS radio occultation data. The NET model is tested against in situ measurements from several missions and shows excellent agreement with the observations, outperforming the state-of-the-art International Reference Ionosphere (IRI) model by up to an order of magnitude, especially at 100-200 km above the F2-layer peak. This study provides a paradigm shift in ionospheric research, by demonstrating that ionospheric densities can be reconstructed with very high fidelity. The NET model depicts the effects of numerous physical processes governing the topside dynamics and can have wide applications in ionospheric research.
Identification of a human estrogen receptor α tetrapeptidic fragment with dual antiproliferative and anti-nociceptive action
Authors: Jouffre Baptiste , Acramel Alexandre , Belnou Mathilde , Santolla Maria Francesca , Talia Marianna , Lappano Rosamaria , Nemati Fariba , Decaudin Didier , Khemtemourian Lucie , Liu Wang-Qing , Maggiolini Marcello , Eschalier Alain , Mallet Christophe , Jacquot Yves
Published: January 2023

The synthetic peptide ERα17p (sequence: PLMIKRSKKNSLALSLT), which corresponds to the 295–311 region of the human estrogen receptor α (ERα), induces apoptosis in breast cancer cells. In mice and at low doses, it promotes not only the decrease of the size of xenografted triple-negative human breast tumors, but also anti-inflammatory and anti-nociceptive effects. Recently, we have shown that these effects were due to its interaction with the seven-transmembrane G protein-coupled estrogen receptor GPER. Following modeling studies, the C-terminus of this peptide (sequence: NSLALSLT) remains compacted at the entrance of the GPER ligand-binding pocket, whereas its N-terminus (sequence: PLMI) engulfs in the depth of the same pocket. Thus, we have hypothesized that the PLMI motif could support the pharmacological actions of ERα17p. Here, we show that the PLMI peptide is, indeed, responsible for the GPER-dependent antiproliferative and anti-nociceptive effects of ERα17p. By using different biophysical approaches, we demonstrate that the NSLALSLT part of ERα17p is responsible for aggregation. Overall, the tetrapeptide PLMI, which supports the action of the parent peptide ERα17p, should be considered as a hit for the synthesis of new GPER modulators with dual antiproliferative and anti-nociceptive actions. This study highlights also the interest to modulate GPER for the control of pain.
Fretting wear behavior of Inconel 718 alloy manufactured by DED and treated by UNSM
Authors: Li Chao , Karimbaev Ruslan , Wang Shengjie , Amanov Auezhan , Wang Dagang , Abdel Wahab Magd
Published: January 2023

Alloy 718 is commonly used in the maritime and aerospace industries due to its strength and durability, particularly in engine rotating components such as disks, fan blades, and high-pressure compressors. As a new type of 3D printing technology, directed energy deposition (DED) can employ lasers to melt metal powders or wires to fabricate arbitrary-shaped workpieces directly from customized data, thereby making machining more synergistic and intuitive. However, the surface properties of the DED-printed alloy 718 samples, such as surface roughness and wear resistance, are typically subpar. By introducing severe plastic deformation to the near-surface, ultrasonic nanocrystal surface modification (UNSM) can be used as a post-processing method and results in altered properties. The uniaxial tensile test reveals that the UNSM-treated alloy 718 exhibits a higher mechanical property. Moreover, using a fretting test rig in accordance with the cylinder-on-plane agreement, a higher wear resistance for UNSM-treated alloy 718 is observed. This study employs the finite element method to fully comprehend the effect of UNSM on wear performance. The fretting wear process of Inconel 718 alloy is established using an energy-based finite element model. Considering the severe practical scenarios, the Johnson–Cook constitutive model is implemented, with the linear isotropic hardening model capturing the plastic behavior. In comparison to experimental measurements, the finite element results demonstrate unprecedented wear loss consistency with an error of less than 2%. Therefore, we conclude that the finite element model built in this study exhibits a high accuracy and can be used to analyze the effect of UNSM on fretting wear behavior. According to finite element analysis, as the normal load increases, the improvement in wear resistance induced by UNSM decreases. Given that the finite element model is based on the energy method, the effects of coefficient of friction (COF) and wear coefficient modified by UNSM are investigated separately. According to the findings, the UNSM-modified COF and wear coefficient play a significant role in determining the wear characteristics. Due to the removal of a substantial amount of material from the central area of the alloy 718 surface by wear, it is also possible to observe that severe plastic strains are primarily concentrated at the edges of the wear scars.
Pulse and pulsating supercharging phenomena in a semi-enclosed pipe
Authors: Wang Fei , Li Heng
Published: January 2023

Considering the discontinuous square pulse wave and continuous sine pulsating wave, we report a distinctive supercharging phenomenon of fluid in a water-filled semi-enclosed pipe and reveal the supercharging regularity. We demonstrate that there can be significant supercharging phenomena at the pipe end-face if the water is periodically injected at the pipe inlet with certain frequency. Compared to the traditional pulsating injection method, the present injection strategy can remarkably enhance the peak pressure of the water at the end face of the pipe. We explained this phenomenon by numerical simulations based on the computational fluid dynamic method. It’s found that there is a quantitative relationship between the optimal pulse frequency, pipe length and wave speed. The proposed frequency model is suitable for the multi-waveform, such as sine wave, square wave and arcuate wave. The fluid pressure at the pipe end-face intermittently increases and the end-face peak pressure is largest when the inlet injection frequency equals to the optimal frequency.
Muscle coordination and recruitment during squat assistance using a robotic ankle–foot exoskeleton
Authors: Jeong Hyeongkeun , Haghighat Parian , Kantharaju Prakyath , Jacobson Michael , Jeong Heejin , Kim Myunghee
Published: January 2023

Squatting is an intensive activity routinely performed in the workplace to lift and lower loads. The effort to perform a squat can decrease using an exoskeleton that considers individual worker’s differences and assists them with a customized solution, namely, personalized assistance. Designing such an exoskeleton could be improved by understanding how the user’s muscle activity changes when assistance is provided. This study investigated the change in the muscle recruitment and activation pattern when personalized assistance was provided. The personalized assistance was provided by an ankle–foot exoskeleton during squatting and we compared its effect with that of the no-device and unpowered exoskeleton conditions using previously collected data. We identified four main muscle recruitment strategies across ten participants. One of the strategies mainly used quadriceps muscles, and the activation level corresponding to the strategy was reduced under exoskeleton assistance compared to the no-device and unpowered conditions. These quadriceps dominant synergy and rectus femoris activations showed reasonable correlations (r = 0.65, 0.59) to the metabolic cost of squatting. These results indicate that the assistance helped reduce quadriceps activation, and thus, the metabolic cost of squatting. These outcomes suggest that the muscle recruitment and activation patterns could be used to design an exoskeleton and training methods.
Maternal control of triploid seed development by the TRANSPARENT TESTA 8 (TT8) transcription factor in Arabidopsis thaliana
Authors: Zumajo-Cardona Cecilia , Aguirre Manuel , Castillo-Bravo Rosa , Mizzotti Chiara , Di Marzo Maurizio , Banfi Camilla , Mendes Marta A. , Spillane Charles , Colombo Lucia , Ezquer Ignacio
Published: January 2023

The balance between parental genome dosage is critical to offspring development in both animals and plants. In some angiosperm species, despite the imbalance between maternally and paternally inherited chromosome sets, crosses between parental lines of different ploidy may result in viable offspring. However, many plant species, likeArabidopsis thaliana, present a post-zygotic reproductive barrier, known as triploid block which results in the inability of crosses between individuals of different ploidy to generate viable seeds but also, in defective development of the seed. Several paternal regulators have been proposed as active players in establishing the triploid block. Maternal regulators known to be involved in this process are some flavonoid biosynthetic (FB) genes, expressed in the innermost layer of the seed coat. Here we explore the role of selected flavonoid pathway genes in triploid block, includingTRANSPARENT TESTA 4(TT4), TRANSPARENT TESTA 7(TT7), SEEDSTICK(STK), TRANSPARENT TESTA 16(TT16), TT8andTRANSPARENT TESTA 13(TT13). This approach allowed us to detect thatTT8, a bHLH transcription factor, member of this FB pathway is required for the paternal genome dosage, as loss of functiontt8, leads to complete rescue of the triploid block to seed development.
Effect of Mo doping in NiO nanoparticles for structural modification and its efficiency for antioxidant, antibacterial applications
Authors: Alam Mir Waqas , BaQais Amal , Mir Tanveer Ahmad , Nahvi Insha , Zaidi Noushi , Yasin Amina
Published: January 2023

Novel molybdenum (Mo)-doped nickel oxide (NiO) Nanoparticles (NPs) were synthesized by using a simple sonochemical methodology and the synthesized NPs were investigated for antioxidant, and antibacterial applications. The X-ray diffraction (XRD) analysis revealed that the crystal systems of rhombohedral (21.34 nm) and monoclinic (17.76 nm) were observed for pure NiO and Mo-doped NiO NPs respectively. The scanning electron microscopy (SEM) results show that the pure NiO NPs possess irregular spherical shape with an average particle size of 93.89 nm while the Mo-doped NiO NPs exhibit spherical morphology with an average particle size of 85.48 nm. The ultraviolet–visible (UV–Vis) spectrum further indicated that the pure and Mo-doped NiO NPs exhibited strong absorption band at the wavelengths of 365 and 349 nm, respectively. The free radical scavenging activity of NiO and Mo-doped NiO NPs was also investigated by utilizing several biochemical assays. The Mo-doped NiO NPs showed better antioxidant activity (84.2%) towards ABTS. + at 200 µg/mL in comparison to their pure counterpart which confirmed that not only antioxidant potency of the doped NPs was better than pure NPs but this efficacy was also concentration dependant as well. The NiO and Mo-doped NiO NPs were further evaluated for their antibacterial activity against gram-positive (Staphylococcus aureus and Bacillus subtilis) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The Mo-doped NiO NPs displayed better antibacterial activity (25 mm) against E. coli in comparison to the pure NPs. The synthesized NPs exhibited excellent aptitude for multi-dimensional applications.
Development of a clinical tool for rating categories of the ICF Rehabilitation Set in Polish practice
Authors: Wiśniowska-Szurlej Agnieszka , Ćwirlej-Sozańska Agnieszka , Wilmowska-Pietruszyńska Anna , Sozański Bernard
Published: January 2023

Rehabilitation is considered a key health strategy in the 21st century. The aim of rehabilitation is to optimize the functioning of patients. The International Classification of Functioning, Disability and Health (ICF) is a framework for describing and organizing information on functioning and disability. Current international efforts to implement ICF in rehabilitation practise include the implementation of ICF Core Sets and operationalize ICF tools for clinics. The aim of the study is to create simple, intuitive descriptions and an initial reference guide for the assessment of the ICF Rehabilitation Set in Polish practice. The development of the Polish version of ICF Rehabilitation Set involved the following steps: (1) identification of ICF Rehabilitation Set categories; (2) development simple, intuitive descriptions; (3) the drafting of the rating reference guide by a multidisciplinary panel following the process employed to develop the Japanese version. The Polish version of ICF Rehabilitation Set, the simple, intuitive descriptions for 29 categories and the rating reference guides were successfully developed. The Polish version of ICF Rehabilitation Set proposed by us is a reference framework for the harmonization of existing information on the functioning and disability of people participating in the rehabilitation process.
1/f laws found in non-human music
Authors: Jermyn Adam S. , Stevenson David J. , Levitin Daniel J.
Published: January 2023

A compelling question at the intersection of physics, neuroscience, and evolutionary biology concerns the extent to which the brains of various species evolved to encode regularities of the physical world. It would be parsimonious and adaptive, for example, for brains to evolve an innate understanding of gravity and the laws of motion, and to be able to detect, auditorily, those patterns of noises that ambulatory creatures make when moving about the world. One such physical regularity of the world is fractal structure, generally characterized by power-law correlations or 1/f β spectral distributions. Such laws are found broadly in nature and human artifacts, from noise in physical systems, to coastline topography (e.g., the Richardson effect), to neuronal spike patterns. These distributions have also been found to hold for the rhythm and power spectral density of a wide array of human music, suggesting that human music incorporates regularities of the physical world that our species evolved to recognize and produce. Here we show for the first time that 1/fβ laws also govern the spectral density of a wide range of animal vocalizations (music), from songbirds, to whales, to howling wolves. We discovered this 1/fβ power-law distribution in the vocalizations within all of the 17 diverse species examined. Our results demonstrate that such power laws are prevalent in the animal kingdom, evidence that their brains have evolved a sensitivity to them as an aid in processing sensory features of the natural world.
A spatial analysis of TB cases and abnormal X-rays detected through active case-finding in Karachi, Pakistan
Authors: Zaidi Syed Mohammad Asad , Jamal Wafa Zehra , Mergenthaler Christina , Azeemi Kiran Sohail , Van Den Berge Nick , Creswell Jacob , Khan Aamir , Khowaja Saira , Habib Shifa Salman
Published: January 2023

Tuberculosis (TB) is the leading cause of avoidable deaths from an infectious disease globally and a large of number of people who develop TB each year remain undiagnosed. Active case-finding has been recommended by the World Health Organization to bridge the case-detection gap for TB in high burden countries. However, concerns remain regarding their yield and cost-effectiveness. Data from mobile chest X-ray (CXR) supported active case-finding community camps conducted in Karachi, Pakistan from July 2018 to March 2020 was retrospectively analyzed. Frequency analysis was carried out at the camp-level and outcomes of interest for the spatial analyses were mycobacterium TB positivity (MTB+) and X-ray abnormality rates. The Global Moran’s I statistic was used to test for spatial autocorrelation for MTB+ and abnormal X-rays within Union Councils (UCs) in Karachi. A total of 1161 (78.1%) camps yielded no MTB+ cases, 246 (16.5%) camps yielded 1 MTB+, 52 (3.5%) camps yielded 2 MTB+ and 27 (1.8%) yielded 3 or more MTB+. A total of 79 (5.3%) camps accounted for 193 (44.0%) of MTB+ cases detected. Statistically significant clustering for MTB positivity (Global Moran’s I: 0.09) and abnormal chest X-rays (Global Moran’s I: 0.36) rates was identified within UCs in Karachi. Clustering of UCs with high MTB positivity were identified in Karachi West district. Statistically significant spatial variation was identified in yield of bacteriologically positive TB cases and in abnormal CXR through active case-finding in Karachi. Cost-effectiveness of active case-finding programs can be improved by identifying and focusing interventions in hotspots and avoiding locations with no known TB cases reported through routine surveillance.
A comprehensive analysis of chromosomal polymorphic variants on reproductive outcomes after intracytoplasmic sperm injection treatment
Authors: Ralapanawe Madara S. B. , Gajaweera Sugandika L. , Karunaratne Nishendra , Dissanayake Vajira H. W. , Price Malcolm J. , Melo Pedro , Coomarasamy Arri , Gallos Ioannis D.
Published: January 2023

Recent studies suggest that chromosomal polymorphic variations are associated with infertility. A systematic review of chromosomal polymorphisms in assisted reproduction found an association with higher rates of miscarriage. Aim of this study is to analyse the influence of specific types or number of chromosomal polymorphic variations on reproductive outcomes of couples undergoing ICSI treatment. We analysed data from 929 fresh and frozen embryo transfer cycles of 692 women who underwent karyotyping analysis using Giemsa-Trypsin-Leishman (GTL) banding prior to the ICSI procedure at the Fertility Centre of Lanka Hospitals Corporation Plc, Sri Lanka, from January 2016 to December 2018. The outcomes of interest were the pregnancy, miscarriage and live birth rate per cycle. There was no evidence of a difference in the reproductive outcomes between carriers or non-carriers of any type or number of chromosomal polymorphic variation. Our data, in contrast to previous studies, does not support a deleterious effect for the type or number of chromosomal polymorphic variations on reproductive outcomes. However, additional prospective, adequately powered studies, conducted in multiethnic populations, are required to further investigate whether the detection of chromosomal polymorphic variants prior to assisted conception may in fact be a futile diagnostic tool.
Mutated genes on ctDNA detecting postoperative recurrence presented reduced neoantigens in primary tumors in colorectal cancer cases
Authors: Nagayama Satoshi , Kobayashi Yuta , Fukunaga Mitsuko , Sakimura Shotaro , Sugimachi Keishi , Sasaki Shin , Masuda Takaaki , Mafune Ken-ichi , Oshima Masanobu , Shibata Tatsuhiro , Suzuki Yutaka , Mimori Koshi
Published: January 2023

The detection and sequencing of the mutated ctDNA is one of the irreplaceable clinical measures in the postoperative management of colorectal cancer (CRC) cases. However, we are curious to comprehend the essential traits of mutated genes comprising metastatic sites out of whole mutated genes in primary sites. In the current retrospective study, we conducted target resequencing of ctDNA using 47 plasma samples and established a cancer panel carrying the commonly mutated genes between primary and recurrent tumors. We found that mutated genes in ctDNA indicated immune-resistance traits with respect to the impaired ability to present neoantigens by loss of expression or binding affinity to HLA in the primary tumor. Compared with the estimated neoantigens from all mutated genes in primary tumors, the neoantigen peptides from commonly mutated genes on the panel showed abundant expression but no binding affinity to HLA. Therefore, ctDNA mutations can be frequently and postoperatively detected to identify recurrence; however, these mutated genes were derived from immune-tolerated clones owing to the loss of neoantigen presentation in primary CRC tumors.
Facile synthesis of NiTe2-Co2Te2@rGO nanocomposite for high-performance hybrid supercapacitor
Authors: Farshadnia Maziar , Ensafi Ali A. , Mousaabadi Kimia Zarean , Rezaei Behzad , Demir Muslum
Published: January 2023

The design of bimetallic tellurides that exhibit excellent electrochemical properties remains a huge challenge for high-performance supercapacitors. In the present study, tellurium is consolidated on CoNi2@rGO for the first time, to synthesize NiTe2-Co2Te2@rGO nanocomposite by using a facile hydrothermal method. As-prepared NiTe2-Co2Te2@rGO nanocomposite was characterized by EDS, TEM, FESEM, Raman, BET, XRD, and XPS techniques to prove the structural transformation. Upon the electrochemical characterization, NiTe2-Co2Te2@rGO has notably presented numerous active sites and enhanced contact sites with the electrolyte solution during the faradic reaction. The as-prepared nanocomposite reveals a specific capacity of 223.6 mAh g−1 in 1.0 M KOH at 1.0 A g-1. Besides, it could retain 89.3% stability after 3000 consecutive galvanostatic charge–discharge cycles at 1.0 A g−1 current density. The hybrid supercapacitor, fabricated by activated carbon as an anode site, and NiTe2-Co2Te2@rGO as a cathode site, presents a potential window of 1.60 V with an energy density of 51 Wh kg−1 and a power density of 800 W kg−1; this electrode is capable of lighting up two red LED lamps and a yellow LED lamp for 20 min, which is connected in parallel. The present work opens new avenues to design and fabrication of nanocomposite electrode materials in the field of supercapacitors.