bluuebunny/crossref_metadata_2025 huggingface dataset:
Against “Normalcy”: A Collective Testimony of Student Workers Organizing During the Pandemic
Authors: Solis Gabriel Antonio , Balderas Tania L. , Pereira Iuri Bauler , Cooney Samantha R. , Gao Cynthia Yuan , Helps David , Malczynski Ramona R. , Mincks Emma B. , Plowright Isobel , Ukockis Joseph A. , Whitmer Lauren
Published: July 2023

In the Spring of 2020, the onset of the global pandemic intensified existing inequalities, but also accelerated organizing within some of the most precarious economic sectors. The neoliberal university was no exception to this general trend, and from 2020 until 2022, student workers organized for union contracts, just pandemic responses, independent arbitration for harassment and improved conditions at their workplaces. In those years, while neoliberal universities issued empty calls for “community,” and a prompt return to normalcy, student workers mobilized themselves and won unprecedented gains from their institutions, rejecting administrative pleas for the defense of the status quo. The following “Report from the Field,” details the struggle of student workers organizing from 2020 to 2022 at the University of New Mexico, the University of Michigan, New York University, and Columbia University, and offers a collectively authored reflection on the challenges, victories and future concerns of its respective movements.
Tool life prediction via SMB-enabled monitor based on BPNN coupling algorithms for sustainable manufacturing
Authors: Chang Wen-Yang , Hsu Bo-Yao
Published: July 2023

The predictive methods of tool wear are usually based on different algorithm predictors, different source data, and different sensing devices for remaining useful life (RUL). In general, it has challenges to model and ensure all of the cutting conditions that are suitable in the actual cutting process for sustainable manufacturing. In order to overcome the doing large amount of experimental data and predict different tool RULs, this study combines the analytical force modeling, the back-propagation neural network (BPNN) machine learning, and the current sensor which all are integrated in smart machine box (SMB) to realize the practical RUL prediction for on-line and real-time applications. The analytical model of the cutting force coefficients of shear and ploughing was established from average cutting forces, it could reduce the experimental number and predict the different cutting conditions. In general, the loading current of the cutting tool from a spindle motor is relatively easier acquired than the resultant forces. Thus, the loading currents of the spindle are used to train and predict the cutting forces using the BPNN model during intelligent manufacturing. The SMB architecture mainly performed the autonomous actions based on the edge layer, the fog layer, and the cloud layer via the TCP/IP, the MQTT protocol, and the unified communication library. Results showed that a predictive error for the ends of the tool life is about 3–10% that are based on the calculating of the cumulative current ratio.
Unravelling the complex sub-ice geology of the Wilkes Subglacial Basin region of East Antarctica from marine sediment provenance analyses
Authors: Pandey Mayuri , Pant Naresh Chandra , Arora Devsamridhi , Ferraccioli Fausto , Gupta Rashmi , Joshi Sonalika
Published: July 2023

Deciphering the sub-ice geology in the Wilkes Subglacial Basin region is important for understanding solid earth-ice sheet evolution and for assessing geological ties between East Antarctica and formerly contiguous Australia. We analyse marine sediment samples derived from drill site U1359 of Integrated Oceanic Drilling Program Expedition 318. Our study reports for the first time that the inland sediment source area comprises a complex mafic igneous terrain and a metamorphosed Precambrian subglacial basement. Pyroxene geochemical analyses confirm the presence of tholeiitic to calc-alkaline basalts. The high-grade part of the subglacial terrain contains upper amphibolite to granulite facies rocks that are comparable to Archaean to Palaeoproterozoic rocks exposed in the Terre Adélie Craton and the formerly adjacent Gawler Craton in Australia. Chemical Th-U-total Pb isochron method (CHIME) ages extracted from a subhedral monazite grain associated with the low-grade biotite-muscovite schist rock fragment provide a unimodal age of 799 ± 13 Ma. Rare occurrences of 800 Ma age in the Terre Adélie Craton and/or George V Coast provide evidence for the presence of at least one late Neoproterozoic magmato-metamorphic event in the interior of Wilkes Land. The affinity of the unexposed geological domains of Wilkes Land, East Antarctica, with their Australian counterparts is discussed in the context of the Rodinia supercontinent.
Post-natal muscle growth and protein turnover: a narrative review of current understanding
Authors: Millward D. Joe
Published: July 2023

A model explaining the dietary-protein-driven post-natal skeletal muscle growth and protein turnover in the rat is updated, and the mechanisms involved are described, in this narrative review. Dietary protein controls both bone length and muscle growth, which are interrelated through mechanotransduction mechanisms with muscle growth induced both from stretching subsequent to bone length growth and from internal work against gravity. This induces satellite cell activation, myogenesis and remodelling of the extracellular matrix, establishing a growth capacity for myofibre length and cross-sectional area. Protein deposition within this capacity is enabled by adequate dietary protein and other key nutrients. After briefly reviewing the experimental animal origins of the growth model, key concepts and processes important for growth are reviewed. These include the growth in number and size of the myonuclear domain, satellite cell activity during post-natal development and the autocrine/paracrine action of IGF-1. Regulatory and signalling pathways reviewed include developmental mechanotransduction, signalling through the insulin/IGF-1–PI3K–Akt and the Ras–MAPK pathways in the myofibre and during mechanotransduction of satellite cells. Likely pathways activated by maximal-intensity muscle contractions are highlighted and the regulation of the capacity for protein synthesis in terms of ribosome assembly and the translational regulation of 5-TOPmRNA classes by mTORC1 and LARP1 are discussed. Evidence for and potential mechanisms by which volume limitation of muscle growth can occur which would limit protein deposition within the myofibre are reviewed. An understanding of how muscle growth is achieved allows better nutritional management of its growth in health and disease.
Affective Interruptions: Political Collectivity in Halftime
Authors: Jennex Craig
Published: July 2023

In this article, I analyze a rhythmic device in musical theater performance that is often used but rarely discussed: The sudden break into halftime. Breaking into halftime—a rhythmic shift that is performed and perceived as occurring at half the tempo (or speed) of the groove in preceding and subsequent sections—has the effect of abruptly stretching out and slowing down musical temporality. With a break into halftime, a song's groove is suddenly broader, more open, and expansive. When accompanied by lyrics, the move suggests deliberateness, calls attention to the lyrical address, and invites a considered response from the listener. It is a musical device akin to drastically slowing down a spoken cadence to ensure that the listener is fully grasping the significance of one's words. With or without lyrics, this temporal disruption has a powerful effect on listeners’ bodies as, suddenly, the established timing of one's musical experience is disrupted and immediately set to half the speed of the previous pace. By analyzing the use of halftime in three filmed musicals—Newsies, Rent, and the Rocky Horror Picture Show—I show how the rhythmic device carries with it social coding of solidarity and collective power among queer, marginalized, and/or otherwise outcast individuals and ultimately alters the broader narrative of the shows. Ultimately, I articulate how halftime serves to queer time and forge collective action, allowing us to reimagine what sort of politics, formations, collectives, and futures are possible.
Remote Sensing Soil Freeze‐Thaw Status and North American N2O Emissions From a Regional Inversion
Authors: Nevison Cynthia , Lan Xin , Ogle Stephen M.
Published: July 2023

North American nitrous oxide (N2O) emissions over 2011–2018 are estimated using the CarbonTracker‐Lagrange regional inversion framework. Emissions are strongest in the Midwestern corn/soybean belt and display a distinct dual maxima seasonal pattern. The first maximum occurs in late winter/early spring, suggestive of freeze‐thaw (FT) effects on denitrification rates and associated N2O emissions. The second maximum occurs in late spring/early summer, consistent with a growing season nitrogen fertilizer‐driven source, although fertilizer applied in late fall may contribute to the FT pulse as well. Interannual variability in the first maximum correlates significantly to soil freeze thaw status derived from remote sensing data. A requisite frozen period in the preceding early winter appears necessary to create conditions for the N2O pulse after thawing. The FT pulse is a prominent feature of the annual cycle in Canadian cropland, where it may be of comparable magnitude to growing season emissions. In contrast, the growing season peak in N2O dominates the FT peak in the Midwestern Corn‐Soybean region of the United States.
Influences Driving and Limiting the Efficacy of Ice Segregation in Alpine Rocks
Authors: Mayer T. , Eppes M. , Draebing D.
Published: July 2023

Rockwall erosion by rockfall is largely controlled by frost weathering in high alpine environments. As alpine rock types are characterized by crack‐dominated porosity and high rock strength, frost cracking observations from low strength and grain supported pore‐space rocks cannot be transferred. Here, we conducted laboratory experiments on Wetterstein limestone samples with different initial crack density and saturation to test their influence on frost cracking efficacy. We exposed rocks to real‐rockwall freezing conditions and monitored acoustic emissions as a proxy for cracking. To differentiate triggers of observed cracking, we modeled ice pressure and thermal stresses. Our results show initial full saturation is not a singular prerequisite for frost cracking. We also observe higher cracking rates in less‐fractured rock. Finally, we find that the temperature threshold for frost cracking in alpine rocks falls below −7°C. Thus, colder, north‐exposed rock faces in the Alps likely experience more frost cracking than southern‐facing counterparts.
SOX17-mediated LPAR4 expression plays a pivotal role in cardiac development and regeneration after myocardial infarction
Authors: Lee Jin-Woo , Lee Choon-Soo , Son HyunJu , Lee Jaewon , Kang Minjun , Chai Jinho , Cho Hyun-Jai , Kim Hyo-Soo
Published: July 2023

Lysophosphatidic acid receptor 4 (LPAR4) exhibits transient expression at the cardiac progenitor stage during pluripotent stem cell (PSC)-derived cardiac differentiation. Using RNA sequencing, promoter analyses, and a loss-of-function study in human PSCs, we discovered that SRY-box transcription factor 17 (SOX17) is an essential upstream factor of LPAR4 during cardiac differentiation. We conducted mouse embryo analyses to further verify our human PSC in vitro findings and confirmed the transient and sequential expression of SOX17 and LPAR4 during in vivo cardiac development. In an adult bone marrow transplantation model using LPAR4 promoter-driven GFP cells, we observed two LPAR4+ cell types in the heart following myocardial infarction (MI). Cardiac differentiation potential was shown in heart-resident LPAR4+ cells, which are SOX17+, but not bone marrow-derived infiltrated LPAR4+ cells. Furthermore, we tested various strategies to enhance cardiac repair through the regulation of downstream signals of LPAR4. During the early stages following MI, the downstream inhibition of LPAR4 by a p38 mitogen-activated protein kinase (p38 MAPK) blocker improved cardiac function and reduced fibrotic scarring compared to that observed following LPAR4 stimulation. These findings improve our understanding of heart development and suggest novel therapeutic strategies that enhance repair and regeneration after injury by modulating LPAR4 signaling.
LY6D is crucial for lipid accumulation and inflammation in nonalcoholic fatty liver disease
Authors: Lee Jibeom , Kim Hyeonhui , Kang Yun-Won , Kim Yumin , Park Moon-young , Song Ji-Hong , Jo Yunju , Dao Tam , Ryu Dongryeol , Lee Junguee , Oh Chang-Myung , Park Sangkyu
Published: July 2023

Nonalcoholic fatty liver disease (NAFLD) is a serious metabolic disorder characterized by excess fat accumulation in the liver. Over the past decade, NAFLD prevalence and incidence have risen globally. There are currently no effective licensed drugs for its treatment. Thus, further study is required to identify new targets for NAFLD prevention and treatment. In this study, we fed C57BL6/J mice one of three diets, a standard chow diet, high-sucrose diet, or high-fat diet, and then characterized them. The mice fed a high-sucrose diet had more severely compacted macrovesicular and microvesicular lipid droplets than those in the other groups. Mouse liver transcriptome analysis identified lymphocyte antigen 6 family member D (Ly6d) as a key regulator of hepatic steatosis and the inflammatory response. Data from the Genotype-Tissue Expression project database showed that individuals with high liver Ly6d expression had more severe NAFLD histology than those with low liver Ly6d expression. In AML12 mouse hepatocytes, Ly6d overexpression increased lipid accumulation, while Ly6d knockdown decreased lipid accumulation. Inhibition of Ly6d ameliorated hepatic steatosis in a diet-induced NAFLD mouse model. Western blot analysis showed that Ly6d phosphorylated and activated ATP citrate lyase, which is a key enzyme in de novo lipogenesis. In addition, RNA- and ATAC-sequencing analyses revealed that Ly6d drives NAFLD progression by causing genetic and epigenetic changes. In conclusion, Ly6d is responsible for the regulation of lipid metabolism, and inhibiting Ly6d can prevent diet-induced steatosis in the liver. These findings highlight Ly6d as a novel therapeutic target for NAFLD.
Arginine 65 methylation of Neurogenin 3 by PRMT1 is required for pancreatic endocrine development of hESCs
Authors: Cho Gahyang , Hyun Kwangbeom , Choi Jieun , Shin Eunji , Kim Bumsoo , Kim Hail , Kim Jaehoon , Han Yong-Mahn
Published: July 2023

Neurogenin 3 (NGN3) is a key transcription factor in the cell fate determination of endocrine progenitors (EPs) in the developing pancreas. Previous studies have shown that the stability and activity of NGN3 are regulated by phosphorylation. However, the role of NGN3 methylation is poorly understood. Here, we report that protein arginine methyltransferase-1 (PRMT1)-mediated arginine 65 methylation of NGN3 is required for the pancreatic endocrine development of human embryonic stem cells (hESCs) in vitro. We found that inducible PRMT1-knockout (P-iKO) hESCs did not differentiate from EPs into endocrine cells (ECs) in the presence of doxycycline. Loss of PRMT1 caused NGN3 accumulation in the cytoplasm of EPs and decreased the transcriptional activity of NGN3. We found that PRMT1 specifically methylates NGN3 arginine 65 and that this modification is a prerequisite for ubiquitin-mediated degradation. Our findings demonstrate that arginine 65 methylation of NGN3 is a key molecular switch in hESCs permitting their differentiation into pancreatic ECs.
High-performance broadband flexible photodetector based on Gd3Fe5O12-assisted double van der Waals heterojunctions
Authors: Zhang Ze , Ji Peirui , Li Shaobo , Wang Fei , He Shengmei , Cheng Yiwei , Zhao Shuhao , Li Kaili , Wang Xiaomin , Wang Yu , Yang Shuming
Published: July 2023

Flexible photodetectors are fundamental components for developing wearable systems, which can be widely used for medical detection, environmental monitoring and flexible imaging. However, compared with 3D materials, low-dimensional materials have degraded performance, a key challenge for current flexible photodetectors. Here, a high-performance broadband photodetector has been proposed and fabricated. By combining the high mobility of graphene (Gr) with the strong light–matter interactions of single-walled carbon nanotubes (SWCNTs) and molybdenum disulfide (MoS2), the flexible photodetector exhibits a greatly improved photoresponse covering the visible to near-infrared range. Additionally, a thin layer of gadolinium iron garnet (Gd3Fe5O12, GdlG) film is introduced to improve the interface of the double van der Waals heterojunctions to reduce the dark current. The SWCNT/GdIG/Gr/GdIG/MoS2 flexible photodetector exhibits a high photoresponsivity of 47.375 A/W and a high detectivity of 1.952 × 1012 Jones at 450 nm, a high photoresponsivity of 109.311 A/W and a high detectivity of 4.504 × 1012 Jones at 1080 nm, and good mechanical stability at room temperature. This work demonstrates the good capacity of GdIG-assisted double van der Waals heterojunctions on flexible substrates and provides a new solution for constructing high-performance flexible photodetectors.
A PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum
Authors: Morano Alexander A. , Rudlaff Rachel M. , Dvorin Jeffrey D.
Published: July 2023

During its asexual blood stage, P. falciparum replicates via schizogony, wherein dozens of daughter cells are formed within a single parent. The basal complex, a contractile ring that separates daughter cells, is critical for schizogony. In this study, we identify a Plasmodium basal complex protein essential for basal complex maintenance. Using multiple microscopy techniques, we demonstrate that PfPPP8 is required for uniform basal complex expansion and maintenance of its integrity. We characterize PfPPP8 as the founding member of a novel family of pseudophosphatases with homologs in other Apicomplexan parasites. By co-immunoprecipitation, we identify two additional new basal complex proteins. We characterize the unique temporal localizations of these new basal complex proteins (late-arriving) and of PfPPP8 (early-departing). In this work, we identify a novel basal complex protein, determine its specific role in segmentation, identify a new pseudophosphatase family, and establish that the P. falciparum basal complex is a dynamic structure.
Anomalous electronic transport in high-mobility Corbino rings
Authors: Vijayakrishnan Sujatha , Poitevin F. , Yu Oulin , Berkson-Korenberg Z. , Petrescu M. , Lilly M. P. , Szkopek T. , Agarwal Kartiek , West K. W. , Pfeiffer L. N. , Gervais G.
Published: July 2023

We report low-temperature electronic transport measurements performed in two multi-terminal Corbino samples formed in GaAs/Al-GaAs two-dimensional electron gases (2DEG) with both ultra-high electron mobility ( ≳ 20 × 106 cm2/ Vs) and with distinct electron density of 1.7 and 3.6 × 1011 cm−2. In both Corbino samples, a non-monotonic behavior is observed in the temperature dependence of the resistance below 1 K. Surprisingly, a sharp decrease in resistance is observed with increasing temperature in the sample with lower electron density, whereas an opposite behavior is observed in the sample with higher density. To investigate further, transport measurements were performed in large van der Pauw samples having identical heterostructures, and as expected they exhibit resistivity that is monotonic with temperature. Finally, we discuss the results in terms of various lengthscales leading to ballistic and hydrodynamic electronic transport, as well as a possible Gurzhi effect.
Cancer lineage-specific regulation of YAP responsive elements revealed through large-scale functional epigenomic screens
Authors: Barbosa Inês A. M. , Gopalakrishnan Rajaraman , Mercan Samuele , Mourikis Thanos P. , Martin Typhaine , Wengert Simon , Sheng Caibin , Ji Fei , Lopes Rui , Knehr Judith , Altorfer Marc , Lindeman Alicia , Russ Carsten , Naumann Ulrike , Golji Javad , Sprouffske Kathleen , Barys Louise , Tordella Luca , Schübeler Dirk , Schmelzle Tobias , Galli Giorgio G.
Published: July 2023

YAP is a key transcriptional co-activator of TEADs, it regulates cell growth and is frequently activated in cancer. In Malignant Pleural Mesothelioma (MPM), YAP is activated by loss-of-function mutations in upstream components of the Hippo pathway, while, in Uveal Melanoma (UM), YAP is activated in a Hippo-independent manner. To date, it is unclear if and how the different oncogenic lesions activating YAP impact its oncogenic program, which is particularly relevant for designing selective anti-cancer therapies. Here we show that, despite YAP being essential in both MPM and UM, its interaction with TEAD is unexpectedly dispensable in UM, limiting the applicability of TEAD inhibitors in this cancer type. Systematic functional interrogation of YAP regulatory elements in both cancer types reveals convergent regulation of broad oncogenic drivers in both MPM and UM, but also strikingly selective programs. Our work reveals unanticipated lineage-specific features of the YAP regulatory network that provide important insights to guide the design of tailored therapeutic strategies to inhibit YAP signaling across different cancer types.
Rapid planning and analysis of high-throughput experiment arrays for reaction discovery
Authors: Mahjour Babak , Zhang Rui , Shen Yuning , McGrath Andrew , Zhao Ruheng , Mohamed Osama G. , Lin Yingfu , Zhang Zirong , Douthwaite James L. , Tripathi Ashootosh , Cernak Tim
Published: July 2023

High-throughput experimentation (HTE) is an increasingly important tool in reaction discovery. While the hardware for running HTE in the chemical laboratory has evolved significantly in recent years, there remains a need for software solutions to navigate data-rich experiments. Here we have developed phactor™, a software that facilitates the performance and analysis of HTE in a chemical laboratory. phactor™ allows experimentalists to rapidly design arrays of chemical reactions or direct-to-biology experiments in 24, 96, 384, or 1,536 wellplates. Users can access online reagent data, such as a chemical inventory, to virtually populate wells with experiments and produce instructions to perform the reaction array manually, or with the assistance of a liquid handling robot. After completion of the reaction array, analytical results can be uploaded for facile evaluation, and to guide the next series of experiments. All chemical data, metadata, and results are stored in machine-readable formats that are readily translatable to various software. We also demonstrate the use of phactor™ in the discovery of several chemistries, including the identification of a low micromolar inhibitor of the SARS-CoV-2 main protease. Furthermore, phactor™ has been made available for free academic use in 24- and 96-well formats via an online interface.
Stratospheric water vapor affecting atmospheric circulation
Authors: Charlesworth Edward , Plöger Felix , Birner Thomas , Baikhadzhaev Rasul , Abalos Marta , Abraham Nathan Luke , Akiyoshi Hideharu , Bekki Slimane , Dennison Fraser , Jöckel Patrick , Keeble James , Kinnison Doug , Morgenstern Olaf , Plummer David , Rozanov Eugene , Strode Sarah , Zeng Guang , Egorova Tatiana , Riese Martin
Published: July 2023

Water vapor plays an important role in many aspects of the climate system, by affecting radiation, cloud formation, atmospheric chemistry and dynamics. Even the low stratospheric water vapor content provides an important climate feedback, but current climate models show a substantial moist bias in the lowermost stratosphere. Here we report crucial sensitivity of the atmospheric circulation in the stratosphere and troposphere to the abundance of water vapor in the lowermost stratosphere. We show from a mechanistic climate model experiment and inter-model variability that lowermost stratospheric water vapor decreases local temperatures, and thereby causes an upward and poleward shift of subtropical jets, a strengthening of the stratospheric circulation, a poleward shift of the tropospheric eddy-driven jet and regional climate impacts. The mechanistic model experiment in combination with atmospheric observations further shows that the prevailing moist bias in current models is likely caused by the transport scheme, and can be alleviated by employing a less diffusive Lagrangian scheme. The related effects on atmospheric circulation are of similar magnitude as climate change effects. Hence, lowermost stratospheric water vapor exerts a first order effect on atmospheric circulation and improving its representation in models offers promising prospects for future research.
Electronic transport driven by collective light-matter coupled states in a quantum device
Authors: Pisani Francesco , Gacemi Djamal , Vasanelli Angela , Li Lianhe , Davies Alexander Giles , Linfield Edmund , Sirtori Carlo , Todorov Yanko
Published: July 2023

In the majority of optoelectronic devices, emission and absorption of light are considered as perturbative phenomena. Recently, a regime of highly non-perturbative interaction, ultra-strong light-matter coupling, has attracted considerable attention, as it has led to changes in the fundamental properties of materials such as electrical conductivity, rate of chemical reactions, topological order, and non-linear susceptibility. Here, we explore a quantum infrared detector operating in the ultra-strong light-matter coupling regime driven by collective electronic excitations, where the renormalized polariton states are strongly detuned from the bare electronic transitions. Our experiments are corroborated by microscopic quantum theory that solves the problem of calculating the fermionic transport in the presence of strong collective electronic effects. These findings open a new way of conceiving optoelectronic devices based on the coherent interaction between electrons and photons allowing, for example, the optimization of quantum cascade detectors operating in the regime of strongly non-perturbative coupling with light.
Phononic bath engineering of a superconducting qubit
Authors: Kitzman J. M. , Lane J. R. , Undershute C. , Harrington P. M. , Beysengulov N. R. , Mikolas C. A. , Murch K. W. , Pollanen J.
Published: July 2023

Phonons, the ubiquitous quanta of vibrational energy, play a vital role in the performance of quantum technologies. Conversely, unintended coupling to phonons degrades qubit performance and can lead to correlated errors in superconducting qubit systems. Regardless of whether phonons play an enabling or deleterious role, they do not typically admit control over their spectral properties, nor the possibility of engineering their dissipation to be used as a resource. Here we show that coupling a superconducting qubit to a bath of piezoelectric surface acoustic wave phonons enables a novel platform for investigating open quantum systems. By shaping the loss spectrum of the qubit via the bath of lossy surface phonons, we demonstrate preparation and dynamical stabilization of superposition states through the combined effects of drive and dissipation. These experiments highlight the versatility of engineered phononic dissipation and advance the understanding of mechanical losses in superconducting qubit systems.
Longevity gene responsible for robust blue organic materials employing thermally activated delayed fluorescence
Authors: Meng Qing-Yu , Wang Rui , Wang Yi-Lei , Guo Xing-Wei , Liu Yu-Qi , Wen Xue-Liang , Yao Cheng-Yu , Qiao Juan
Published: July 2023

The 3rd-Gen OLED materials employing thermally-activated delayed fluorescence (TADF) combine advantages of first two for high-efficiency and low-cost devices. Though urgently needed, blue TADF emitters have not met stability requirement for applications. It is essential to elucidate the degradation mechanism and identify the tailored descriptor for material stability and device lifetime. Here, via in-material chemistry, we demonstrate chemical degradation of TADF materials involves critical role of bond cleavage at triplet state rather than singlet, and disclose the difference between bond dissociation energy of fragile bonds and first triplet state energy (BDE-ET1) is linearly correlated with logarithm of reported device lifetime for various blue TADF emitters. This significant quantitative correlation strongly reveals the degradation mechanism of TADF materials have general characteristic in essence and BDE-ET1 could be the shared “longevity gene”. Our findings provide a critical molecular descriptor for high-throughput-virtual-screening and rational design to unlock the full potential of TADF materials and devices.
Site-specific bioorthogonal protein labelling by tetrazine ligation using endogenous β-amino acid dienophiles
Authors: Richter Daniel , Lakis Edgars , Piel Jörn
Published: July 2023

The tetrazine ligation is an inverse electron-demand Diels–Alder reaction widely used for bioorthogonal modifications due to its versatility, site specificity and fast reaction kinetics. A major limitation has been the incorporation of dienophiles in biomolecules and organisms, which relies on externally added reagents. Available methods require the incorporation of tetrazine-reactive groups by enzyme-mediated ligations or unnatural amino acid incorporation. Here we report a tetrazine ligation strategy, termed TyrEx (tyramine excision) cycloaddition, permitting autonomous dienophile generation in bacteria. It utilizes a unique aminopyruvate unit introduced by post-translational protein splicing at a short tag. Tetrazine conjugation occurs rapidly with a rate constant of 0.625 (15) M−1 s−1 and was applied to produce a radiolabel chelator-modified Her2-binding Affibody and intracellular, fluorescently labelled cell division protein FtsZ. We anticipate the labelling strategy to be useful for intracellular studies of proteins, as a stable conjugation method for protein therapeutics, as well as other applications.
Demonstration of momentum cooling to enhance the potential of cancer treatment with proton therapy
Authors: Maradia Vivek , Meer David , Dölling Rudolf , Weber Damien C. , Lomax Antony J. , Psoroulas Serena
Published: July 2023

In recent years, there has been a considerable push towards ultrahigh dose rates in proton therapy to effectively utilize motion mitigation strategies and potentially increase the sparing of healthy tissue through the so-called FLASH effect. However, in cyclotron-based proton therapy facilities, it is difficult to reach ultrahigh dose rates for low-energy beams. The main reason for this lies in the large momentum spread that such beams have after reducing their energy to levels required for proton therapy, incurring large losses in conventionally used momentum or energy selection slits. Here we propose momentum cooling by using a wedge in the energy selection system (instead of a slit) to reduce the momentum spread of the beam without introducing substantial beam losses. We demonstrate this concept in our eye treatment beamline and obtain a factor of two higher transmission, which could eventually halve the treatment delivery time. Furthermore, we show that with a gantry design incorporating this feature, we can achieve almost a factor of 100 higher transmission for a 70 MeV beam compared with conventional cyclotron-based facilities. This concept could enhance the potential of proton therapy by opening up possibilities of treating new indications and reducing the cost.
Physics-informed reinforcement learning for motion control of a fish-like swimming robot
Authors: Rodwell Colin , Tallapragada Phanindra
Published: July 2023

Motion control of fish-like swimming robots presents many challenges due to the unstructured environment and unmodelled governing physics of the fluid–robot interaction. Commonly used low-fidelity control models using simplified formulas for drag and lift forces do not capture key physics that can play an important role in the dynamics of small-sized robots with limited actuation. Deep Reinforcement Learning (DRL) holds considerable promise for motion control of robots with complex dynamics. Reinforcement learning methods require large amounts of training data exploring a large subset of the relevant state space, which can be expensive, time consuming, or unsafe to obtain. Data from simulations can be used in the initial stages of DRL, but in the case of swimming robots, the complexity of fluid–body interactions makes large numbers of simulations infeasible from the perspective of time and computational resources. Surrogate models that capture the primary physics of the system can be a useful starting point for training a DRL agent which is subsequently transferred to train with a higher fidelity simulation. We demonstrate the utility of such physics-informed reinforcement learning to train a policy that can enable velocity and path tracking for a planar swimming (fish-like) rigid Joukowski hydrofoil. This is done through a curriculum where the DRL agent is first trained to track limit cycles in a velocity space for a representative nonholonomic system, and then transferred to train on a small simulation data set of the swimmer. The results show the utility of physics-informed reinforcement learning for the control of fish-like swimming robots.
Impact of corn processing and weaning age on calf performance, blood metabolites, rumen fermentation, and behavior
Authors: Rahimi A. , Ghorbani G. R. , Hashemzadeh F. , Mirzaei M. , Saberipour H. R. , Ahmadi F. , Ghaffari M. H.
Published: July 2023

This study examined the impact of two corn processing methods (steam-flaked (SFC) vs. ground) combined with two weaning ages (50 or 75 days) on calf performance, blood metabolites, rumen fermentation, nutrient digestion, and behavior. The study involved 48 three-day-old Holstein calves, with an average body weight of 41.4 ± 2.2 kg. The experimental design was a 2 × 2 factorial arrangement, resulting in four treatment groups: SFC50 (SFC and weaning at 50 days), SFC75 (SFC and weaning at 75 days), GC50 (ground corn and weaning at 50 days), and GC75 (ground corn and weaning at 75 days). Calves were given whole milk at 4 L/ day from day 3–15 and 7 L/ day from day 16 to either 43 or 68, depending on weaning age. Weaning occurred between days 44 and 50 for early-weaned calves and between days 69 and 75 for late-weaned calves. The study lasted until calves were 93 days old. The starter ration consisted of soybean meal, corn grain, 5% chopped wheat straw and premix. Results indicated that the SFC-based starter feed improved calf performance and nutrient digestion, as evidenced by increased weight gain, dry matter, crude protein, and neutral detergent fiber digestibility. Calves fed the SFC-based starter diet had lower blood albumin and urea N concentrations, while blood total protein and globulin concentrations were higher, especially in early-weaned calves. No significant changes in rumen pH and ammonia-N concentration were observed. In addition, the SFC starter feed resulted in higher volatile fatty acids concentration and longer feeding time in weaned calves compared to ground corn. Overall, these results suggest that an SFC-based starter feed may be beneficial for both early and late weaned calves.
The genomic and transcriptomic landscape of advanced renal cell cancer for individualized treatment strategies
Authors: de Joode K. , van de Geer W. S. , van Leenders G. J. L. H. , Hamberg P. , Westgeest H. M. , Beeker A. , Oosting S. F. , van Rooijen J. M. , Beerepoot L. V. , Labots M. , Mathijssen R. H. J. , Lolkema M. P. , Cuppen E. , Sleijfer S. , van de Werken H. J. G. , van der Veldt A. A. M.
Published: July 2023

Differences in the clinical course and treatment responses in individual patients with advanced renal cell carcinoma (RCC) can largely be explained by the different genomics of this disease. To improve the personalized treatment strategy and survival outcomes for patients with advanced RCC, the genomic make-up in patients with advanced RCC was investigated to identify putative actionable variants and signatures. In this prospective multicenter study (NCT01855477), whole-genome sequencing (WGS) data of locally advanced and metastatic tissue biopsies and matched whole-blood samples were collected from 91 patients with histopathologically confirmed RCC. WGS data were analyzed for small somatic variants, copy-number alterations and structural variants. For a subgroup of patients, RNA sequencing (RNA-Seq) data could be analyzed. RNA-Seq data were clustered on immunogenic and angiogenic gene expression patterns according to a previously developed angio-immunogenic gene signature. In all patients with papillary and clear cell RCC, putative actionable drug targets were detected by WGS, of which 94% were on-label available. RNA-Seq data of clear cell and papillary RCC were clustered using a previously developed angio-immunogenic gene signature. Analyses of driver mutations and RNA-Seq data revealed clear differences among different RCC subtypes, showing the added value of WGS and RNA-Seq over clinicopathological data. By improving both histological subtyping and the selection of treatment according to actionable targets and immune signatures, WGS and RNA-Seq may improve therapeutic decision making for most patients with advanced RCC, including patients with non-clear cell RCC for whom no standard treatment is available to data. Prospective clinical trials are needed to evaluate the impact of genomic and transcriptomic diagnostics on survival outcome for advanced RCC patients.
Survival analysis of a stochastic impulsive single-species population model with migration driven by environmental toxicant
Authors: Dai Xiangjun , Jiao Jianjun , Quan Qi
Published: July 2023

Considering the influence of environmental toxicant on population migration between patches, we propose and study a stochastic impulsive single-species population model with migration driven by environmental toxicant in this paper. We first discuss the existence and uniqueness of global positive solutions of the model by constructing the Lyapunov function. Then, we obtain sufficient conditions for extinction, stochastic persistence and persistence in the mean of the single-species population. Finally, we present some numerical simulations to illustrate our results. These results provide insights for the conservation and management of species in polluted environments.
Bacterial community structure in the rumen and hindgut is associated with nitrogen efficiency in Holstein cows
Authors: De La Guardia-Hidrogo V. M. , Paz H. A.
Published: July 2023

Nitrogen efficiency (Neff; milk N/N intake) in dairy cows is limited and most of the consumed N is excreted in manure. Despite the crucial role of the gastrointestinal microbiome on N metabolism, associations between bacterial communities at different sections and Neff are not fully elucidated. Enhanced understanding of host-microbiome interactions can provide insights to improve Neff in dairy cows. Twenty-three Holstein cows were selected, and their Neff were determined using a N balance approach. From the cohort of cows, six cows were classified as low Neff and five cows as high Neff and their rumen and fecal bacterial communities were profiled using amplicon sequence variants (ASV) based on 16S rRNA gene sequencing. Then, relationships between differentially abundant bacterial features and Neff were evaluated. Neff in low and high cows averaged 22.8 and 30.3%, respectively. With similar N intake, high Neff cows wasted less N in manure compared to low Neff cows (P < 0.01, 11.0 ± 0.59 vs 14.3 ± 0.54 g of N/kg of milk). Rumen fermentation and plasma profiles were similar between Neff groups, but for plasma Gln which was greater (P = 0.02) in high compared to low Neff cows. In both rumen and feces, the phylogenetic composition of the bacterial communities was similar (P ≥ 0.65) between Neff groups, but differences were observed at the species -level (amplicon sequence variants). In the rumen, differentially abundant species from the genus Prevotella showed strong positive correlations with Neff, whereas in feces, differentially abundant species from the class Clostridia showed strong negative correlations with Neff. Our results revealed that Holstein cows with divergent Neff display distinctive bacterial community structure at the species-level in both the rumen and feces. Strong correlations between differentially abundant species and Neff in both sample sites, support the importance of the rumen bacterial composition on productive responses and suggest a more relevant role of the hindgut microbiome. Targeting both pre- and post-gastric bacterial communities may provide novel opportunities to enhance Neff in dairy cows.
Heat transfer analysis of buoyancy opposing radiated flow of alumina nanoparticles scattered in water-based fluid past a vertical cylinder
Authors: Alharbi Sayer Obaid , Khan Umair , Zaib Aurang , Ishak Anuar , Raizah Zehba , Eldin Sayed M. , Pop Ioan
Published: July 2023

Cooling and heating are two critical processes in the transportation and manufacturing industries. Fluid solutions containing metal nanoparticles have higher thermal conductivity than conventional fluids, allowing for more effective cooling. Thus, the current paper is a comparative exploration of the time-independent buoyancy opposing and heat transfer flow of alumina nanoparticles scattered in water as a regular fluid induced via a vertical cylinder with mutual effect of stagnation-point and radiation. Based on some reasonable assumptions, the model of nonlinear equations is developed and then tackled numerically employing the built-in bvp4c MATLAB solver. The impacts of assorted control parameters on gradients are investigated. The outcomes divulge that the aspect of friction factor and heat transport upsurge by incorporating alumina nanoparticles. The involvement of the radiation parameter shows an increasing tendency in the heat transfer rate, resulting in an enhancement in thermal flow efficacy. In addition, the temperature distribution uplifts due to radiation and curvature parameters. It is discerned that the branch of dual outcomes exists in the opposing flow case. Moreover, for higher values of the nanoparticle volume fraction, the reduced shear stress and the reduced heat transfer rate increased respectively by almost 1.30% and 0.0031% for the solution of the first branch, while nearly 1.24%, and 3.13% for the lower branch solution.
Identification of novel biomarkers and immune infiltration features of recurrent pregnancy loss by machine learning
Authors: Luo Yujia , Zhou Yuanyuan
Published: July 2023

Recurrent pregnancy loss (RPL) is a complex reproductive disorder. The incompletely understood pathophysiology of RPL makes early detection and exact treatment difficult. The purpose of this work was to discover optimally characterized genes (OFGs) of RPL and to investigate immune cell infiltration in RPL. It will aid in better understanding the etiology of RPL and in the early detection of RPL. The RPL-related datasets were obtained from the Gene Expression Omnibus (GEO), namely GSE165004 and GSE26787. We performed functional enrichment analysis on the screened differentially expressed genes (DEGs). Three machine learning techniques are used to generate the OFGs. A CIBERSORT analysis was conducted to examine the immune infiltration in RPL patients compared with normal controls and to investigate the correlation between OFGs and immune cells. Between the RPL and control groups, 42 DEGs were discovered. These DEGs were found to be involved in cell signal transduction, cytokine receptor interactions, and immunological response, according to the functional enrichment analysis. By integrating OFGs from the LASSO, SVM-REF, and RF algorithms (AUC > 0.880), we screened for three down-regulated genes: ZNF90, TPT1P8, FGF2, and an up-regulated FAM166B. Immune infiltration study revealed that RPL samples had more monocytes (P < 0.001) and fewer T cells (P = 0.005) than controls, which may contribute to RPL pathogenesis. Additionally, all OFGs linked with various invading immune cells to varying degrees. In conclusion, ZNF90, TPT1P8, FGF2, and FAM166B are potential RPL biomarkers, offering new avenues for research into the molecular mechanisms of RPL immune modulation and early detection.
The Elk-3 target Abhd10 ameliorates hepatotoxic injury and fibrosis in alcoholic liver disease
Authors: Li Tian-Zhu , Bai Chun-Ying , Wu Bao , Zhang Cong-Ying ,   SIRIGULENG, Wang Wen-Tao , Shi Tie-Wei , Zhou Jing
Published: July 2023

Alcoholic liver disease (ALD) and other forms of chronic hepatotoxic injury can lead to transforming growth factor β1 (TGFβ1)-induced hepatic fibrosis and compromised liver function, underscoring the need to develop novel treatments for these conditions. Herein, our analyses of liver tissue samples from severe alcoholic hepatitis (SAH) patients and two murine models of ALD reveals that the ALD phenotype was associated with upregulation of the transcription factor ETS domain-containing protein (ELK-3) and ELK-3 signaling activity coupled with downregulation of α/β hydrolase domain containing 10 (ABHD10) and upregulation of deactivating S-palmitoylation of the antioxidant protein Peroxiredoxin 5 (PRDX5). In vitro, we further demonstrate that ELK-3 can directly bind to the ABHD10 promoter to inhibit its transactivation. TGFβ1 and epidermal growth factor (EGF) signaling induce ABHD10 downregulation and PRDX5 S-palmitoylation via ELK-3. This ELK-3-mediated ABHD10 downregulation drives oxidative stress and disrupts mature hepatocyte function via enhancing S-palmitoylation of PRDX5’s Cys100 residue. In vivo, ectopic Abhd10 overexpression ameliorates liver damage in ALD model mice. Overall, these data suggest that the therapeutic targeting of the ABHD10-PRDX5 axis may represent a viable approach to treating ALD and other forms of hepatotoxicity.
Thermodynamics, statistical mechanics and the vanishing pore width limit of confined fluids
Authors: Dong W. , Franosch T. , Schilling R.
Published: July 2023

Temperature, particle number and volume are the independent variables of the Helmholtz free energy for a bulk fluid. For a fluid confined in a slit pore between two walls, they are usually complemented by the surface area. However, an alternative choice is possible with the volume replaced by the pore width. Although the formulations with such two sets of independent variables are different, we show they are equivalent and present their relations. Corresponding general statistical-mechanics results are also presented. When the pore width becomes very small, the system behaves rather like a two-dimensional (2D) fluid and one can wonder if thermodynamics still holds. We find it remains valid even in the limit of vanishing pore width and show how to treat the divergences in the normal pressure and the chemical potential so that the corresponding 2D results can be obtained. Thus, we show that the Gibbs surface thermodynamics is perfectly capable of describing small systems.