bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granular Cooling of Uni‐Sized Inelastic Particles in an Obstructed Chute
Authors: Mendes Solange V. , Ferreira Rui M. L. , Aleixo Rui , Larcher Michele , Amaral Sílvia 
Published: October 2024

AbstractThis research aims to experimentally characterize cooling, clogging and jamming of a dry granular flow in a chute partially obstructed by a stopping wall with two slits adjacent to the side walls. We ensemble‐average velocities, determined with Particle Tracking Velocimetry, and its fluctuations, to compute mean flow and granular temperature fields. Full chute‐wide jamming is triggered by the formation of stable arch‐like clogging structures in front of the slits. The statistical distribution of the clogging instant is not heavy‐tailed, which indicates that clogging occurs only when the flow through the slits is liquid‐like. An upstream‐progressing jamming wave eventually forms, similar to that observed in fully obstructed chutes. There is no triple point anywhere, since the flow cools down to a granular liquid before jamming. We identified three main stages of jamming wave propagation. The initial buildup is characterized by high values of the upstream Froude number, slow progression, and transformation of kinetic into potential energy. This occurs with significant granular head losses, as particles attempt to flow over the jam. In the second stage, accretion becomes dominant, characterized by smaller head losses and, consequently, higher values of the jamming wave celerity. In the third stage, the jamming wave propagates against a cooler but faster flow that pushes against the jam, slightly increasing the wave strength. Accretion is the main mechanism of jammed mass increase, justifying a further increase of wave acceleration. The macroscopic aspects of the jamming wave dynamics can be described, as a first approximation, by shallow‐water theory.
Quantifying Dissolution Dynamics in Porous Media Using a Spatial Flow Focusing Profile
Authors: Szawełło Tomasz , Hyman Jeffrey D. , Kang Peter K. , Szymczak Piotr 
Published: October 2024

AbstractThe diverse range of patterns in porous media formed by dissolution processes depends on the relative magnitude of flow, transport, and chemical reactions at pore surfaces. However, distinguishing between regimes often relies solely on qualitative, visual comparisons of emergent structures. Here, we propose a quantitative measure capable of identifying different regimes using the concept of the spatial flow focusing profile, which segments the medium into cross sections along the flow direction to calculate the flow focusing index for each section. We employ this measure in numerical simulations of a dissolving porous medium using a pore network model. We obtain a morphological phase diagram of dissolution patterns, which we characterize using the flow focusing profile. In particular, we demonstrate that analyzing the temporal changes in the profile allows one to quantitatively distinguish between wormholing and channeling. The transition between them is shown to be affected by the heterogeneity of the system.
Water Column Nitrogen Removal During Storms in a Low‐Order Watershed
Authors: Bacmeister E. , Peck E. , Bernasconi S. , Inamdar S. , Kan J. , Peipoch Marc 
Published: October 2024

AbstractWater column removal in streams is a nitrogen (N) cycling pathway that has been historically overlooked. Studies filling this knowledge gap have focused on the role of water column N removal in mid‐to‐large‐order rivers with consistently high suspended sediment concentrations. However, smaller streams may provide comparable suspended sediment concentrations during and after storm events, creating favorable conditions for water column N removal. To assess the presence, magnitude, and control of water column N removal during storms in low‐order watersheds, we measured water column denitrification and heterotrophic assimilatory N uptake rates at three locations in a Mid‐Atlantic watershed during five storm events of different magnitude, sediment loads, and nutrient availability. We found large variations in water column denitrification (0–5.56 mg N g−1 d−1) and assimilatory uptake (0.003–1.67 mg N g−1 d−1). Higher rates of N removal occurred during flow recession, with a correlation between suspended sediment organic matter content and denitrification. On average, denitrification rates in the water column were higher when flashy responses to storm events occurred. In contrast to denitrification, water column N removal rates (as both denitrification and heterotrophic assimilation) during storm events were comparable to those measured at baseflow in larger rivers. However, water column denitrification could only account for less than 10% of potential reach‐scale N removal during most of the storm events. Our findings provide insight into the ecological relevance of small stream water columns and suggest that more research is needed to understand the magnitude of stream water column processing on watershed‐scale N removal.
Ultra‐wide Band Antipodal Vivaldi Antenna Using Metasurface Lens for Gain and Front‐To‐Back Ratio (FBR) Improvement
Authors: Zambak Muhammad Fitra , Johari Safpbri , Mohd Yassin Mohd Najib , Ismail Arif Marwardi , Alghaihab Abdullah 
Published: October 2024

AbstractThis paper addresses the limited gain of conventional Antipodal Vivaldi Antenna (AVA) at higher frequencies. We propose a novel Metamaterial Lens Vivaldi Antenna (MLVA) design that overcomes this limitation by integrating an exponentially tapered antenna lens and a strategically placed Near Zero Refractive Index (NRZI) metamaterial lattice. The MLVA achieves exceptional wideband performance with a −3 dB gain bandwidth exceeding 148.6% from 3.7 to 25 GHz. The result demonstrates a peak realized gain of 11.8 dBi at 11.2 GHz, compared to 9.1 dBi conventional AVA, especially beyond 5 GHz. The compact MLVA design measures only 120 × 78 × 1.524 mm3 (1.48 × 0.96 × 0.0188λ03) λ0 where free‐space wavelength is the lowest frequency and is fabricated on RO4350 B substrate with a 50‐Ω SMA connector. Key features of the design include exponential flaring, and trapezoidal lens geometries chosen for their inherent ability to effectively collimate and direct the spherical wavefront. The incorporation of a dielectric lens and metasurface further enhances gain and Front‐to‐Back Ratio (FBR) by directing the majority of energy in the end‐fire direction. Experimental results validate the effectiveness of the proposed design, confirming simulation predictions. These outstanding characteristics make the MLVA a promising candidate for diverse wireless communication and radar applications demanding high data rates across a broad frequency range.
InGaP χ(2) integrated photonics platform for broadband, ultra-efficient nonlinear conversion and entangled photon generation
Authors: Akin Joshua , Zhao Yunlei , Misra Yuvraj , Haque A. K. M. Naziul , Fang Kejie 
Published: October 2024

AbstractNonlinear optics plays an important role in many areas of science and technology. The advance of nonlinear optics is empowered by the discovery and utilization of materials with growing optical nonlinearity. Here we demonstrate an indium gallium phosphide (InGaP) integrated photonics platform for broadband, ultra-efficient second-order nonlinear optics. The InGaP nanophotonic waveguide enables second-harmonic generation with a normalized efficiency of 128, 000%/W/cm2at 1.55μm pump wavelength, nearly two orders of magnitude higher than the state of the art in the telecommunication C band. Further, we realize an ultra-bright, broadband time-energy entangled photon source with a pair generation rate of 97 GHz/mW and a bandwidth of 115 nm centered at the telecommunication C band. The InGaP entangled photon source shows high coincidence-to-accidental counts ratio CAR > 104and two-photon interference visibility > 98%. The InGaP second-order nonlinear photonics platform will have wide-ranging implications for non-classical light generation, optical signal processing, and quantum networking.
Immunotherapy for glioblastoma: current state, challenges, and future perspectives
Authors: Liu Yang , Zhou Fei , Ali Heba , Lathia Justin D. , Chen Peiwen 
Published: October 2024

AbstractGlioblastoma (GBM) is an aggressive and lethal type of brain tumor in human adults. The standard of care offers minimal clinical benefit, and most GBM patients experience tumor recurrence after treatment. In recent years, significant advancements have been made in the development of novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance in many advanced cancers. However, the benefit of immune-based treatments in GBM is limited because of the unique brain immune profiles, GBM cell heterogeneity, and immunosuppressive tumor microenvironment. In this review, we present a detailed overview of current immunotherapeutic strategies and discuss the challenges and potential molecular mechanisms underlying immunotherapy resistance in GBM. Furthermore, we provide an in-depth discussion regarding the strategies that can overcome immunotherapy resistance in GBM, which will likely require combination therapies.
Exploration of vanoxerine analogues as antibacterial agents
Authors: Kingdon Alexander D. H. , Adcock Holly V. , Kasimati Eleni-Marina , Craven Philip , van Schaik Willem , Cox Liam R. , Besra Gurdyal S. 
Published: October 2024

AbstractMycobacterium tuberculosis is a bacterial pathogen, responsible for approximately 1.3 million deaths in 2022 through tuberculosis infections. The complex treatment regimen required to treat tuberculosis and growing rates of drug resistance, necessitates the development of new anti-mycobacterial agents. One approach is to repurpose drugs from other clinical applications. Vanoxerine (GBR 12909) was previously shown to have anti-mycobacterial activity, through dissipating the membrane electric potential and hence, cellular energetics. Several vanoxerine analogues were synthesised in this study, which exhibited a range of activities against mycobacteria and enterococcus. All active analogues had similar impacts on the membrane electric potential and inhibition of ethidium bromide efflux. The most active compound displayed reduced inhibitory activity against the known human target of vanoxerine, the dopamine transporter. This work has identified a promising analogue, which could provide a starting point for further medicinal chemistry and drug development efforts to target mycobacteria.
Extensive iron–water exchange at Earth’s core–mantle boundary can explain seismic anomalies
Authors: Kawano Katsutoshi , Nishi Masayuki , Kuwahara Hideharu , Kakizawa Sho , Inoue Toru , Kondo Tadashi 
Published: October 2024

AbstractSeismological observations indicate the presence of chemical heterogeneities at the lowermost mantle, just above the core–mantle boundary (CMB), sparking debate over their origins. A plausible explanation for the enigmatic seismic wave velocities observed in ultra-low-velocity zones (ULVZs) is the process of iron enrichment from the core to the silicate mantle. However, traditional models based on diffusion of atoms and penetration of molten iron fail to account for the significant iron enrichment observed in ULVZs. Here, we show that the chemical reaction between silicate bridgmanite and iron under hydrous conditions leads to profound iron enrichment within silicate, a process not seen in anhydrous conditions. Our findings suggest that the interaction between the core and mantle facilitates deep iron enrichment over a few kilometres at the bottom of the mantle when water is present. We propose that the seismic signatures observed in ULVZs indicate whole mantle convection, accompanied by deep water cycles from the crust to the core through Earth’s history.
Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders
Authors: Kroupova Alena , Spiteri Valentina A. , Rutter Zoe J. , Furihata Hirotake , Darren Darren , Ramachandran Sarath , Chakraborti Sohini , Haubrich Kevin , Pethe Julie , Gonzales Denzel , Wijaya Andre J. , Rodriguez-Rios Maria , Sturbaut Manon , Lynch Dylan M. , Farnaby William , Nakasone Mark A. , Zollman David , Ciulli Alessio 
Published: October 2024

AbstractThe ubiquitin E3 ligase cereblon (CRBN) is the target of therapeutic drugs thalidomide and lenalidomide and is recruited by most targeted protein degraders (PROTACs and molecular glues) in clinical development. Biophysical and structural investigation of CRBN has been limited by current constructs that either require co-expression with the adaptor DDB1 or inadequately represent full-length protein, with high-resolution structures of degrader ternary complexes remaining rare. We present the design of CRBNmidi, a construct that readily expresses from E. coli with high yields as soluble, stable protein without DDB1. We benchmark CRBNmidi for wild-type functionality through a suite of biophysical techniques and solve high-resolution co-crystal structures of its binary and ternary complexes with degraders. We qualify CRBNmidi as an enabling tool to accelerate structure-based discovery of the next generation of CRBN based therapeutics.
Adaptive laboratory evolution recruits the promiscuity of succinate semialdehyde dehydrogenase to repair different metabolic deficiencies
Authors: He Hai , Gómez-Coronado Paul A. , Zarzycki Jan , Barthel Sebastian , Kahnt Jörg , Claus Peter , Klein Moritz , Klose Melanie , de Crécy-Lagard Valérie , Schindler Daniel , Paczia Nicole , Glatter Timo , Erb Tobias J. 
Published: October 2024

AbstractPromiscuous enzymes often serve as the starting point for the evolution of novel functions. Yet, the extent to which the promiscuity of an individual enzyme can be harnessed several times independently for different purposes during evolution is poorly reported. Here, we present a case study illustrating how NAD(P)+-dependent succinate semialdehyde dehydrogenase of Escherichia coli (Sad) is independently recruited through various evolutionary mechanisms for distinct metabolic demands, in particular vitamin biosynthesis and central carbon metabolism. Using adaptive laboratory evolution (ALE), we show that Sad can substitute for the roles of erythrose 4-phosphate dehydrogenase in pyridoxal 5’-phosphate (PLP) biosynthesis and glyceraldehyde 3-phosphate dehydrogenase in glycolysis. To recruit Sad for PLP biosynthesis and glycolysis, ALE employs various mechanisms, including active site mutation, copy number amplification, and (de)regulation of gene expression. Our study traces down these different evolutionary trajectories, reports on the surprising active site plasticity of Sad, identifies regulatory links in amino acid metabolism, and highlights the potential of an ordinary enzyme as innovation reservoir for evolution.
High sensitivity cameras can lower spatial resolution in high-resolution optical microscopy
Authors: Ortkrass Henning , Müller Marcel , Engdahl Anders Kokkvoll , Holst Gerhard , Huser Thomas 
Published: October 2024

AbstractHigh-resolution optical fluorescence microscopies and, in particular, super-resolution fluorescence microscopy, are rapidly adopting highly sensitive cameras as their preferred photodetectors. Camera-based parallel detection facilitates high-speed live cell imaging with the highest spatial resolution. Here, we show that the drive to use ever more sensitive, photon-counting image sensors in cameras can, however, have detrimental effects on the spatial resolution of the resulting images. This is particularly noticeable in applications that demand a high space-bandwidth product, where the image magnification is close to the Nyquist sampling limit of the sensor. Most scientists will often select image sensors based on parameters such as pixel size, quantum efficiency, signal-to-noise performance, dynamic range, and frame rate of the sensor. A parameter that is, however, typically overlooked is the sensor’s modulation transfer function (MTF). We have determined the wavelength-specific MTF of front- and back-illuminated image sensors and evaluated how it affects the spatial resolution that can be achieved in high-resolution fluorescence microscopy modalities. We find significant differences in image sensor performance that cause the resulting spatial resolution to vary by up to 28%. This result shows that the choice of image sensor has a significant impact on the imaging performance of all camera-based optical microscopy modalities.
Centrioles are frequently amplified in early B cell development but dispensable for humoral immunity
Authors: Schapfl Marina A. , LoMastro Gina M. , Braun Vincent Z. , Hirai Maretoshi , Levine Michelle S. , Kiermaier Eva , Labi Verena , Holland Andrew J. , Villunger Andreas 
Published: October 2024

AbstractCentrioles define centrosome structure and function. Deregulation of centriole numbers can cause developmental defects and cancer. The p53 tumor suppressor limits the growth of cells lacking or harboring additional centrosomes and can be engaged by the “mitotic surveillance” or the “PIDDosome pathway”, respectively. Here, we show that early B cell progenitors frequently present extra centrioles, ensuing their high proliferative activity and related DNA damage. Extra centrioles are efficiently cleared during B cell maturation. In contrast, centriole loss upon Polo-like kinase 4 (Plk4) deletion causes apoptosis and arrests B cell development. This defect can be rescued by co-deletion of Usp28, a critical component of the mitotic surveillance pathway, that restores cell survival and maturation. Centriole-deficient mature B cells are proliferation competent and mount a humoral immune response. Our findings imply that progenitor B cells are intolerant to centriole loss but permissive to centriole amplification, a feature potentially facilitating their malignant transformation.
Interpretable spatially aware dimension reduction of spatial transcriptomics with STAMP
Authors: Zhong Chengwei , Ang Kok Siong , Chen Jinmiao 
Published: October 2024

AbstractSpatial transcriptomics produces high-dimensional gene expression measurements with spatial context. Obtaining a biologically meaningful low-dimensional representation of such data is crucial for effective interpretation and downstream analysis. Here, we present Spatial Transcriptomics Analysis with topic Modeling to uncover spatial Patterns (STAMP), an interpretable spatially aware dimension reduction method built on a deep generative model that returns biologically relevant, low-dimensional spatial topics and associated gene modules. STAMP can analyze data ranging from a single section to multiple sections and from different technologies to time-series data, returning topics matching known biological domains and associated gene modules containing established markers highly ranked within. In a lung cancer sample, STAMP delineated cell states with supporting markers at a higher resolution than the original annotation and uncovered cancer-associated fibroblasts concentrated on the tumor edge’s exterior. In time-series data of mouse embryonic development, STAMP disentangled the erythro-myeloid hematopoiesis and hepatocytes developmental trajectories within the liver. STAMP is highly scalable and can handle more than 500,000 cells.
Ongoing transmission of trachoma in low prevalence districts in Mozambique: results from four cross-sectional enhanced impact surveys, 2022
Authors: Sitoe Henis Mior , Oswald William E. , Zita Felizmina , Fall Mawo , Momade Tamimo , Adams Molly W. , Flueckiger Rebecca M. , McPherson Scott , Eyob Sabrina , Doan Thuy , Lietman Thomas M. , Arnold Benjamin F. , Wickens Karana , Gwyn Sarah , Martin Diana L. , Kasubi Mabula , Boyd Sarah , Bakhtiari Ana , Jimenez Cristina , Solomon Anthony W. , Harding-Esch Emma M. , Mwingira Upendo J. , Ngondi Jeremiah M. 
Published: October 2024

AbstractMozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation—follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1–9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1–9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF < 5% had SCR of 5.0 and 4.7. The district with TF ≥ 5% had a SCR of 6.0. This enhanced TIS furthered understanding of transmission in these districts and provides information on additional indicators for monitoring trachoma programs.
Precision comparison of intensity ratios and area ratios in spectral analysis
Authors: Hagiwara Yuuki , Kuwatani Tatsu 
Published: October 2024

AbstractThe long-debated question in analytical chemistry of which of the area ratio or the intensity ratio is the more precise has yielded no definitive analytical conclusion. To address this issue theoretically, we derived analytical solutions for the lower limits of estimation precision for spectral parameters, including the intensity ratio and area ratio, based on the Cramér–Rao lower bound (CRLB) framework for a Gaussian spectrum. The precisions of spectral parameter estimations from the analytical solutions were consistent with results obtained from Monte Carlo simulations. Our theoretical and simulation results revealed that the precision of estimating the area ratio surpassed that of the intensity ratio by a factor of $$\sqrt{2}$$

2

. Additionally, our experimental results aligned well with both theoretical predictions and simulation outcomes, further validating our approach. This increased precision of the area ratio is due to negative covariance between intensity and bandwidth, rather than the area containing more intensity information, as often misinterpreted. Consequently, and quite counter intuitively, prior bandwidth and intensity related information does not improve the area ratio precision: it worsens it. The analytical solution we derived represents the fundamental limits of spectral parameter measurement precision. Thus, it can be used as an alternative method for estimating the minimum error when experimental measurement uncertainty cannot be determined.