bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of Coupled Upper Troposphere and Boundary Layer Induces Two Types of Short‐Term Heavy Rainfall Along the Eastern Foothills of the Taihang Mountains
Authors: Li Yan , Wang Qingyu , Wei Yue , Tang Jianping 
Published: October 2024

AbstractUsing 11 years of hourly merged rainfall records and ERA reanalysis data, this paper reveals two major circulation modes leading to two types of short‐term heavy rainfall (STHR) along the Taihang Mountains' eastern foothills, and further explains their mechanisms. One circulation mode has a distinct warm anomaly at 300 hPa covering most areas of North China, together with the boundary‐layer westerly anomaly occurring in North China and its southern region (UTWA‐BLWA). UTWA‐BLWA effectively contributes to the reinforcement of the upper‐level divergence and the low‐level moisture convergence by promoting the strengthening of upper anticyclonic and low‐level southwesterly anomalies. The combined effects of low‐level jet (LLJ) and topographic uplift form the central‐northern STHR pattern. The other circulation structure has a 300‐hPa warm anomaly located to the southeastern Russia and a prominent 300‐hPa cold anomaly covering the south, together with the boundary‐layer easterly anomaly occurring over the whole region of eastern China (UTCA‐BLEA). The southern STHR pattern is attributed to the exit of the boundary‐layer jet (BLJ) over lower elevations due to moist transport and dynamic uplift associated with the easterly anomaly. The results indicate that the locations of STHR are related to the direction, intensity, and height of the LLJ. The findings highlight that the upper‐tropospheric temperature anomalies (UTTA) and boundary‐layer easterly flow jointly modulate heavy rainfall. Analysis of the coupled upper troposphere and boundary layer could help understand and forecast heavy rainfall.
Calving Dynamics and the Potential Impact of Mélange Buttressing at the Western Calving Front of Thwaites Glacier, West Antarctica
Authors: Crawford Anna , Åström Jan , Benn Douglas I. , Luckman Adrian , Gladstone Rupert , Zwinger Thomas , Robertsén Fredrik , Bevan Suzanne 
Published: October 2024

AbstractThe western region of the wide Thwaites Glacier terminus is characterized by a near‐vertical calving front. The grounding line at this western calving front (WCF) rests on a relatively high ridge, behind which exists a reverse‐sloping bed; retreat of the grounding line into this over‐deepening basin could therefore expose deep calving faces that may be subject to ice‐cliff failure. Here, we use the 3D Helsinki Discrete Element Model to identify the factors that control the calving dynamics in this location. We then focus on the ability of mélange to influence these dynamics given the wide embayment in which Thwaites Glacier terminates. We find that calving along the WCF is currently influenced by ice flow across the grounding line and consequent longitudinal tensile stress and rift formation. Calving is slowed in simulations that are initiated with a highly constricted mélange, with a thicker mélange suppressing calving entirely. We liken the constrained simulations to a scenario in which mélange piles behind a large grounded iceberg. In a future which may see calving become a more dominant control on the retreat of Thwaites Glacier, this type of blockage will be necessary for robust force chains to develop and transmit resistive forces to the terminus. The ability of the mélange to hinder calving at this location will be determined by the presence and rigidity of binding land‐fast sea ice and iceberg keel depths. Therefore, it is necessary to represent calving, mélange and sea ice in a single framework to predict the fate of Thwaites Glacier.
An Integrated Machine Learning Workflow to Estimate In Situ Stresses Based on Downhole Sonic Logs and Laboratory Triaxial Ultrasonic Velocity Data
Authors: Mustafa Ayyaz , Kelley Mark , Lu Guanyi , Bunger Andrew P. 
Published: October 2024

AbstractThe optimum performance of various subsurface operations such as stimulation treatments, wellbore drilling, horizontal well placement, underground mining, and tunneling rely on accurate estimation of the in situ stresses. This study presents an integrated machine learning (ML) workflow for the reliable determination of the in situ stress in subsurface rock formations. The study workflow was completed in three phases. In the first phase, six supervised ML regression techniques were employed to develop the stress prediction models using laboratory true triaxial ultrasonic velocity tests (labTUV) data of subsurface rock samples retrieved from well 16A(78)‐32 located at the Utah FORGE geothermal site. In the second phase, subsurface geological formations were classified into rock facies using an unsupervised K‐means clustering algorithm. Finally, in the third phase, the optimized ML models were employed for predicting the in situ stresses in the corresponding rock facies in the well 16A(78)‐32 using field sonic logs. A comparison of evaluation metrics revealed the superior performance of ANN models for horizontal and vertical stress predictions with root mean squared error of 1.5, 0.6, and 1.7 MPa, and determination coefficient (R2) of 0.98, 0.98, and 0.96, for the testing/validation phases, respectively. The generalization capability of ML models was explored by uncovering the underlying physics. The mathematical expressions of constitutive relations were extracted from three ANN models. Further, a total of five rock facies were identified in the subsurface geological formations. The novel workflow would be capable of delivering reliable in situ stress profiles in subsurface geological formations without performing expensive field tests.
Assessment of the Weimer Geomagnetic Perturbation Model for High‐Latitude Positioning and Navigation
Authors: Califf S. , Nair M. , Weimer D. , Zachman N. , Poedjono B. 
Published: October 2024

AbstractThe Geomagnetism Group at the National Centers for Environmental Information (NCEI), in collaboration with the Cooperative Institute for Research in Environmental Sciences (CIRES), along with various government and industry partners, specializes in developing and providing access to Earth's internal magnetic field models. These models are crucial for applications such as compass navigation and wellbore positioning, offering reference values for the geomagnetic field (total field, dip or inclination, and declination) at any location across the Earth. This study assesses the Weimer geomagnetic perturbation model, proposed by Weimer in 2013, which is an empirical model of magnetic field variations at high latitudes driven by solar wind measurements, as a candidate for capturing geomagnetic field variations in high‐latitude areas. We compare the geomagnetic field variations predicted by the Weimer model against data from the INTERMAGNET and SuperMAG observatory networks. Our findings indicate that the Weimer model achieves a reduction in the standard deviations of high‐latitude magnetic field variations by approximately 20%–30% once quiet‐time baselines are removed from the data set. Furthermore, we compare the performance of the Weimer model against the Space Weather Modeling Framework's Geospace model during specific geomagnetic storms in 2017 and 2018, and we find that the Weimer model is more effective in predicting magnetic variations at high latitudes than the Geospace model during these storms. Additionally, comparisons to magnetometer data collected from high‐latitude directional‐drilling operations align with the trends observed in comparisons with INTERMAGNET and SuperMAG observatory data, confirming the Weimer model's reliability and effectiveness for such applications.
USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer
Authors: Reissland Michaela , Hartmann Oliver , Tauch Saskia , Bugter Jeroen M. , Prieto-Garcia Cristian , Schulte Clemens , Loebbert Sinah , Solvie Daniel , Bitman-Lotan Eliya , Narain Ashwin , Jacomin Anne-Claire , Schuelein-Voelk Christina , Fuss Carmina T. , Pahor Nikolett , Ade Carsten , Buck Viktoria , Potente Michael , Li Vivian , Beliu Gerti , Wiegering Armin , Grossmann Tom , Eilers Martin , Wolf Elmar , Maric Hans , Rosenfeldt Mathias , Maurice Madelon M. , Dikic Ivan , Gallant Peter , Orian Amir , Diefenbacher Markus E. 
Published: October 2024

Abstract
The contribution of deubiquitylating enzymes (DUBs) to β-Catenin stabilization in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, and by using an unbiassed screen, we discovered that the DUB USP10 stabilizes β-Catenin specifically in APC-truncated CRC in vitro and in vivo. Mechanistic studies, including in vitro binding together with computational modelling, revealed that USP10 binding to β-Catenin is mediated via the unstructured N-terminus of USP10 and is outcompeted by intact APC, favouring β-catenin degradation. However, in APC-truncated cancer cells USP10 binds to β-catenin, increasing its stability which is critical for maintaining an undifferentiated tumour identity. Elimination of USP10 reduces the expression of WNT and stem cell signatures and induces the expression of differentiation genes. Remarkably, silencing of USP10 in murine and patient-derived CRC organoids established that it is essential for NOTUM signalling and the APC super competitor-phenotype, reducing tumorigenic properties of APC-truncated CRC. These findings are clinically relevant as patient-derived organoids are highly dependent on USP10, and abundance of USP10 correlates with poorer prognosis of CRC patients. Our findings reveal, therefore, a role for USP10 in CRC cell identity, stemness, and tumorigenic growth by stabilising β-Catenin, leading to aberrant WNT signalling and degradation resistant tumours. Thus, USP10 emerges as a unique therapeutic target in APC truncated CRC.
Identifying the best candidate for focal therapy: a comprehensive review
Authors: Ghoreifi Alireza , Gomella Leonard , Hu Jim C. , Konety Badrinath , Lunelli Luca , Rastinehad Ardeshir R. , Salomon Georg , Taneja Samir , Tourinho-Barbosa Rafael , Lebastchi Amir H. 
Published: October 2024

Abstract
Background
Despite the evidence supporting the use of focal therapy (FT) in patients with localized prostate cancer (PCa), considerable variability exists in the patient selection criteria across current studies. This study aims to review the most recent evidence concerning the optimal approach to patient selection for FT in PCa.

Methods
PubMed database was systematically queried for studies reporting patient selection criteria in FT for PCa before December 31, 2023. After excluding non-relevant articles and a quality assessment, data were extracted, and results were described qualitatively.

Results
There is no level I evidence regarding the best patient selection approach for FT in patients with PCa. Current international multidisciplinary consensus statements recommend multiparametric magnetic resonance imaging (mpMRI) followed by MRI-targeted and systematic biopsy for all candidates. FT may be considered in clinically localized, intermediate risk (Gleason 3 + 4 and 4 + 3), and preferably unifocal disease. Patients should have an acceptable life expectancy. Those with prostate volume >50 ml and erectile dysfunction should not be excluded from FT. Prostate-specific antigen (PSA) level of < 20 (ideally < 10) ng/mL is recommended. However, the utility of other molecular and genomic biomarkers in patient selection for FT remains unknown.

Conclusions
FT may be considered in well-selected patients with localized PCa. This review provides a comprehensive insight regarding the optimal approach for patient selection in FT.
TP53: the unluckiest of genes?
Authors: Joerger Andreas C. , Stiewe Thorsten , Soussi Thierry 
Published: October 2024

Abstract
The transcription factor p53 plays a key role in the cellular defense against cancer development. It is inactivated in virtually every tumor, and in every second tumor this inactivation is due to a mutation in the TP53 gene. In this perspective, we show that this diverse mutational spectrum is unique among all other cancer-associated proteins and discuss what drives the selection of TP53 mutations in cancer. We highlight that several factors conspire to make the p53 protein particularly vulnerable to inactivation by the mutations that constantly plague our genome. It appears that the TP53 gene has emerged as a victim of its own evolutionary past that shaped its structure and function towards a pluripotent tumor suppressor, but came with an increased structural fragility of its DNA-binding domain. TP53 loss of function - with associated dominant-negative effects - is the main mechanism that will impair TP53 tumor suppressive function, regardless of whether a neomorphic phenotype is associated with some of these variants.
Oncometabolites at the crossroads of genetic, epigenetic and ecological alterations in cancer
Authors: Lanzetti Letizia 
Published: October 2024

AbstractBy the time a tumor reaches clinical detectability, it contains around 108–109 cells. However, during tumor formation, significant cell loss occurs due to cell death. In some estimates, it could take up to a thousand cell generations, over a ~ 20-year life-span of a tumor, to reach clinical detectability, which would correspond to a “theoretical” generation of ~1030 cells. These rough calculations indicate that cancers are under negative selection. The fact that they thrive implies that they “evolve”, and that their evolutionary trajectories are shaped by the pressure of the environment. Evolvability of a cancer is a function of its heterogeneity, which could be at the genetic, epigenetic, and ecological/microenvironmental levels [1]. These principles were summarized in a proposed classification in which Evo (evolutionary) and Eco (ecological) indexes are used to label cancers [1]. The Evo index addresses cancer cell-autonomous heterogeneity (genetic/epigenetic). The Eco index describes the ecological landscape (non-cell-autonomous) in terms of hazards to cancer survival and resources available. The reciprocal influence of Evo and Eco components is critical, as it can trigger self-sustaining loops that shape cancer evolvability [2]. Among the various hallmarks of cancer [3], metabolic alterations appear unique in that they intersect with both Evo and Eco components. This is partly because altered metabolism leads to the accumulation of oncometabolites. These oncometabolites have traditionally been viewed as mediators of non-cell-autonomous alterations in the cancer microenvironment. However, they are now increasingly recognized as inducers of genetic and epigenetic modifications. Thus, oncometabolites are uniquely positioned at the crossroads of genetic, epigenetic and ecological alterations in cancer. In this review, the mechanisms of action of oncometabolites will be summarized, together with their roles in the Evo and Eco phenotypic components of cancer evolvability. An evolutionary perspective of the impact of oncometabolites on the natural history of cancer will be presented.
Long non-coding RNA-encoded micropeptides: functions, mechanisms and implications
Authors: Xiao Yinan , Ren Yaru , Hu Wenteng , Paliouras Athanasios R. , Zhang Wenyang , Zhong Linghui , Yang Kaixin , Su Li , Wang Peng , Li Yonghong , Ma Minjie , Shi Lei 
Published: October 2024

AbstractLong non-coding RNAs (lncRNAs) are typically described as RNA transcripts exceeding 200 nucleotides in length, which do not code for proteins. Recent advancements in technology, including ribosome RNA sequencing and ribosome nascent-chain complex sequencing, have demonstrated that many lncRNAs retain small open reading frames and can potentially encode micropeptides. Emerging studies have revealed that these micropeptides, rather than lncRNAs themselves, are responsible for vital functions, including but not limited to regulating homeostasis, managing inflammation and the immune system, moderating metabolism, and influencing tumor progression. In this review, we initially outline the rapidly advancing computational analytical methods and public tools to predict and validate the potential encoding of lncRNAs. We then focus on the diverse functions of micropeptides and their underlying mechanisms in the pathogenesis of disease. This review aims to elucidate the functions of lncRNA-encoded micropeptides and explore their potential applications as therapeutic targets in cancer.
Scalable watermarking for identifying large language model outputs
Authors: Dathathri Sumanth , See Abigail , Ghaisas Sumedh , Huang Po-Sen , McAdam Rob , Welbl Johannes , Bachani Vandana , Kaskasoli Alex , Stanforth Robert , Matejovicova Tatiana , Hayes Jamie , Vyas Nidhi , Merey Majd Al , Brown-Cohen Jonah , Bunel Rudy , Balle Borja , Cemgil Taylan , Ahmed Zahra , Stacpoole Kitty , Shumailov Ilia , Baetu Ciprian , Gowal Sven , Hassabis Demis , Kohli Pushmeet 
Published: October 2024

AbstractLarge language models (LLMs) have enabled the generation of high-quality synthetic text, often indistinguishable from human-written content, at a scale that can markedly affect the nature of the information ecosystem1–3. Watermarking can help identify synthetic text and limit accidental or deliberate misuse4, but has not been adopted in production systems owing to stringent quality, detectability and computational efficiency requirements. Here we describe SynthID-Text, a production-ready text watermarking scheme that preserves text quality and enables high detection accuracy, with minimal latency overhead. SynthID-Text does not affect LLM training and modifies only the sampling procedure; watermark detection is computationally efficient, without using the underlying LLM. To enable watermarking at scale, we develop an algorithm integrating watermarking with speculative sampling, an efficiency technique frequently used in production systems5. Evaluations across multiple LLMs empirically show that SynthID-Text provides improved detectability over comparable methods, and standard benchmarks and human side-by-side ratings indicate no change in LLM capabilities. To demonstrate the feasibility of watermarking in large-scale-production systems, we conducted a live experiment that assessed feedback from nearly 20 million Gemini6 responses, again confirming the preservation of text quality. We hope that the availability of SynthID-Text7 will facilitate further development of watermarking and responsible use of LLM systems.
A transcriptomic hourglass in brown algae
Authors: Lotharukpong Jaruwatana Sodai , Zheng Min , Luthringer Rémy , Liesner Daniel , Drost Hajk-Georg , Coelho Susana M. 
Published: October 2024

AbstractComplex multicellularity has emerged independently across a few eukaryotic lineages and is often associated with the rise of elaborate, tightly coordinated developmental processes1,2. How multicellularity and development are interconnected in evolution is a major question in biology. The hourglass model of embryonic evolution depicts how developmental processes are conserved during evolution, and predicts morphological and molecular divergence in early and late embryogenesis, bridged by a conserved mid-embryonic (phylotypic) period linked to the formation of the basic body plan3,4. Initially found in animal embryos5–8, molecular hourglass patterns have recently been proposed for land plants and fungi9,10. However, whether the hourglass pattern is an intrinsic feature of all complex multicellular eukaryotes remains unknown. Here we tested the presence of a molecular hourglass in the brown algae, a eukaryotic lineage that has evolved multicellularity independently from animals, fungi and plants1,11,12. By exploring transcriptome evolution patterns of brown algae with distinct morphological complexities, we uncovered an hourglass pattern during embryogenesis in morphologically complex species. Filamentous algae without canonical embryogenesis display transcriptome conservation in multicellular stages of the life cycle, whereas unicellular stages are more rapidly evolving. Our findings suggest that transcriptome conservation in brown algae is associated with cell differentiation stages, but is not necessarily linked to embryogenesis. Together with previous work in animals, plants and fungi, we provide further evidence for the generality of a developmental hourglass pattern across complex multicellular eukaryotes.
Machine-guided design of cell-type-targeting cis-regulatory elements
Authors: Gosai Sager J. , Castro Rodrigo I. , Fuentes Natalia , Butts John C. , Mouri Kousuke , Alasoadura Michael , Kales Susan , Nguyen Thanh Thanh L. , Noche Ramil R. , Rao Arya S. , Joy Mary T. , Sabeti Pardis C. , Reilly Steven K. , Tewhey Ryan 
Published: October 2024

AbstractCis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing and stimulus responses, which collectively define the thousands of unique cell types in the body1–3. While there is great potential for strategically incorporating CREs in therapeutic or biotechnology applications that require tissue specificity, there is no guarantee that an optimal CRE for these intended purposes has arisen naturally. Here we present a platform to engineer and validate synthetic CREs capable of driving gene expression with programmed cell-type specificity. We take advantage of innovations in deep neural network modelling of CRE activity across three cell types, efficient in silico optimization and massively parallel reporter assays to design and empirically test thousands of CREs4–8. Through large-scale in vitro validation, we show that synthetic sequences are more effective at driving cell-type-specific expression in three cell lines compared with natural sequences from the human genome and achieve specificity in analogous tissues when tested in vivo. Synthetic sequences exhibit distinct motif vocabulary associated with activity in the on-target cell type and a simultaneous reduction in the activity of off-target cells. Together, we provide a generalizable framework to prospectively engineer CREs from massively parallel reporter assay models and demonstrate the required literacy to write fit-for-purpose regulatory code.
A subcortical feeding circuit linking an interoceptive node to jaw movement
Authors: Kosse Christin , Ivanov Jessica , Knight Zachary , Pellegrino Kyle , Friedman Jeffrey 
Published: October 2024

AbstractThe brain processes an array of stimuli, enabling the selection of appropriate behavioural responses, but the neural pathways linking interoceptive inputs to outputs for feeding are poorly understood1–3. Here we delineate a subcortical circuit in which brain-derived neurotrophic factor (BDNF)-expressing neurons in the ventromedial hypothalamus (VMH) directly connect interoceptive inputs to motor centres, controlling food consumption and jaw movements. VMHBDNF neuron inhibition increases food intake by gating motor sequences of feeding through projections to premotor areas of the jaw. When food is unavailable, VMHBDNF inhibition elicits consummatory behaviours directed at inanimate objects such as wooden blocks, and inhibition of perimesencephalic trigeminal area (pMe5) projections evokes rhythmic jaw movements. The activity of these neurons is decreased during food consumption and increases when food is in proximity but not consumed. Activity is also increased in obese animals and after leptin treatment. VMHBDNF neurons receive monosynaptic inputs from both agouti-related peptide (AgRP) and proopiomelanocortin neurons in the arcuate nucleus (Arc), and constitutive VMHBDNF activation blocks the orexigenic effect of AgRP activation. These data indicate an Arc → VMHBDNF → pMe5 circuit that senses the energy state of an animal and regulates consummatory behaviours in a state-dependent manner.