bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amnesties as a means of encouraging transition and strengthening the application of IHL in Colombia: The case of the Special Jurisdiction for Peace
Authors: Giraldo Muñoz Marcela 
Published: October 2024

Abstract
Bearing in mind that the peace process between the Colombian government and the Revolutionary Armed Forces of Colombia – People's Army (Fuerzas Armadas Revolucionarias de Colombia – Ejército del Pueblo, FARC-EP) has been an important milestone for transitional justice, this article aims to share some of the good practices and achievements of this process, as well as the setbacks and challenges that could be avoided in future peace processes. The article will highlight relevant contributions from the Chamber for Amnesty or Pardon (CAP) such as impacting the resocialization of former FARC-EP members and developing international humanitarian law discussions in relation to war crimes and less serious crimes. Additionally, it will describe some of the main challenges faced by the CAP, such as the high number of applications for transitional benefits that it receives, the high number of proceedings that it supervises, and the security concerns arising from implementing a peace agreement in a country still in conflict.
A Multi‐Sensor Approach for the Characterization of Tropical Cyclone Induced Swell—Application to TC Larry, 2021
Authors: Pouplin Clément , Mouche Alexis , Chapron Bertrand 
Published: October 2024

AbstractSea states are likely highly complex and variable under tropical cyclone (TC) conditions. Outrunning the inner core TC vortex, swell systems can radiate in different directions with different wavelengths. Jointly using several sources of wave observations, it is demonstrated that directional properties of wave fields induced by a TC can now be very well recovered. Directional wave information extracted from Sentinel‐1 wave mode and CFOSAT SWIM are combined with Sofar Spotter drifters and NDBC buoy network. Specific filtering is applied to deal with respective limitations of these observation systems. High consistency between the different data sources is generally obtained, to provide evolving directional distributions of radiating swell systems during the whole TC life time. TC wave properties can then trace particular events associated to extended fetch effects, quantifying the asymmetrical directional wavelength distributions, as function of the TC main characteristics evolving with time (intensity, size, translation).
Experiments on Constriction‐Pool‐Widening Morphology in Bedrock Canyons
Authors: Kusack Kyle M. , Li Tingan , Venditti Jeremy G. 
Published: October 2024

AbstractBedrock rivers often alternate between relatively wide unconstrained reaches and conspicuously narrow deep incised bedrock reaches (canyons). These bedrock canyons exhibit a constriction‐pool‐widening (CPW) morphology that consists of a lateral constriction, a deeply scoured pool formed downstream of the constriction, and a channel widening at or near the pool exit. To explore how CPWs are formed in bedrock canyons, we hypothesize that the lateral constriction at the canyon entrance forces a CPW to form allogenically with subsequent CPWs propagating further downstream. Our hypothesis was tested experimentally in a flume channel with a forced lateral constriction at the canyon entrance. Our experiment shows that the forced constriction can cause a primary CPW to form allogenically because the backwater upstream of the forced constriction causes sediment deposition that creates an elevation drop, promoting flow and sediment to plunge toward the bed and carve a primary pool. Channel widening occurs at the primary pool exit because sediment deposit forms that deflects sediment into the banks, causing lateral erosion. Downstream of the primary widening, channel width declines and a new lateral constriction forms, which causes the formation of pools and widening downstream, resulting in downstream CPW propagation. In our experiment, the bedrock channel evolved until a persistent alluvial cover formed, reaching a steady state morphology without further vertical erosion until perturbed by higher discharge. Our experiment shows that discharge variation is necessary for a channel to evolve in the absence of uplift.
PET clinical study of novel antipsychotic LB-102 demonstrates unexpectedly prolonged dopamine receptor target engagement
Authors: Wong Dean F. , Chand Ganesh B. , Caito Nicole , Eramo Anna , Grattan Vincent T. , Hixon Mark S. , Nicol Ginger , Lessie Erin , Prensky Zachary , Kuwabara Hiroto , Tian Lucy , Valenta Ines , Schindler Thomas H. , Gründer Gerhard , Vaino Andrew R. 
Published: October 2024

Abstract
Regulation of dopamine activity has important clinical consequences, most notably in schizophrenia. LB-102, N-methyl amisulpride, is a novel dopamine D2/3/5-HT7 inhibitor being developed as a treatment for schizophrenia and other psychiatric disorders. The characteristic that is common to all current antipsychotics is their engagement of D2 dopamine receptors. The goal of this study was to measure the dopamine receptor occupancy of orally administered LB-102 at three different doses (50, 75, and 100 mg as single doses and 50 and 100 mg as multiple doses) and at different timepoints in healthy volunteers using positron emission tomography (PET) with 11C raclopride as a radiotracer. Results of this study (NCT04588129) showed that steady-state once daily oral dosing of 50 mg LB-102 afforded striatal dopamine occupancy (RO) in the desired 60–80% range consistently over the course of 24 h. Contrary to the often observed relationship between RO vs plasma concentrations, maximum dopamine RO significantly lagged maximum plasma concentration and showed little variability under steady state conditions. A similar phenomenon has recently been reported with a non-racemic version of amisulpride [1]. LB-102 was generally safe and well-tolerated at all doses. Results of this study were used to inform dosing in a subsequent Phase 2 clinical study in schizophrenia patients.
TMEM209 promotes hepatocellular carcinoma progression by activating the Wnt/β-catenin signaling pathway through KPNB1 stabilization
Authors: Fang Haoran , Shi Xiaoyi , Gao Jie , Yan Zhiping , Wang Yun , Chen Yabin , Zhang Jiacheng , Guo Wenzhi 
Published: October 2024

AbstractHepatocellular carcinoma (HCC) is the most common malignancy in the liver, with a poor prognosis. Transmembrane protein 209 (TMEM209) involves multiple biological processes, such as substance transportation and signal transduction, and is abundantly expressed in tumor tissues. However, the relationship between TMEM209 and HCC has not been comprehensively elucidated. In this study, we aimed to illustrate this issue by in vitro and in vivo experiments. Bioinformatic analysis and clinical sample validation revealed that TMEM209 was upregulated in HCC and correlated with reduced survival duration. Functionally, TMEM209 promoted the proliferation, migration, invasion, and EMT of HCC cells in vitro and facilitated tumor growth and metastasis in xenograft models. Mechanistically, TMEM209 promoted the proliferation and metastasis of HCC in a KPNB1-dependent manner. Specifically, TMEM209 could bind to KPNB1, thereby competitively blocking the interaction between KPNB1 and the E3 ubiquitin ligase RING finger and CHY zinc finger domain-containing protein 1 (RCHY1) and preventing K48-associated ubiquitination degradation of KPNB1. Ultimately, the Wnt/β-catenin signaling pathway was activated, contributing to the progression of the malignant phenotype of HCC. In conclusion, the molecular mechanism underlying the TMEM209/KPNB1/Wnt/β-catenin axis in HCC progression was elucidated. TMEM209 is a potential biomarker and therapeutic target for HCC.
Single-cell spatiotemporal analysis reveals alveolar dendritic cell–T cell immunity hubs defending against pulmonary infection
Authors: Cong Boyi , Dong Xuan , Yang Zongheng , Yu Pin , Chai Yangyang , Liu Jiaqi , Zhang Meihan , Zang Yupeng , Kang Jingmin , Feng Yu , Liu Yi , Feng Weimin , Wang Dehe , Deng Wei , Li Fengdi , Song Zhiqi , Wang Ziqiao , Chen Xiaosu , Qin Hua , Yu Qinyi , Li Zhiqing , Liu Shuxun , Xu Xun , Zhong Nanshan , Ren Xianwen , Qin Chuan , Liu Longqi , Wang Jian , Cao Xuetao 
Published: October 2024

AbstractHow immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell–T cell immunity hubs, where Ccr7+Ido1+ dendritic cells, Cd160+Cd8+ T cells, and Tnfrsf4+Cd4+ T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9+ macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity.
Impacts of the feedback loop between sense-antisense RNAs in regulating circadian rhythms
Authors: Uriu Koichiro , Hernandez-Sanchez Juan P. , Kojima Shihoko 
Published: October 2024

AbstractAntisense transcripts are a unique group of non-coding RNAs and play regulatory roles in a variety of biological processes, including circadian rhythms. Per2AS is an antisense transcript to the sense core clock gene Period2 (Per2) in mouse and its expression is rhythmic and antiphasic to Per2. To understand the impact of Per2AS-Per2 interaction, we developed a new mathematical model that mechanistically described the mutually repressive relationship between Per2 and Per2AS. This mutual repression can regulate both amplitude and period of circadian oscillation by affecting a negative feedback regulation of Per2. Simulations from this model also fit with experimental observations that could not be fully explained by our previous model. Our revised model can not only serve as a foundation to build more detailed models to better understand the impact of Per2AS-Per2 interaction in the future, but also be used to analyze other sense-antisense RNA pairs that mutually repress each other.
A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2
Authors: Reguzova Alena , Müller Melanie , Pagallies Felix , Burri Dominique , Salomon Ferdinand , Rziha Hanns-Joachim , Bittner-Schrader Zsofia , Verstrepen Babs E. , Böszörményi Kinga P. , Verschoor Ernst J. , Gerhauser Ingo , Elbers Knut , Esen Meral , Manenti Alessandro , Monti Martina , Rammensee Hans-Georg , Derouazi Madiha , Löffler Markus W. , Amann Ralf 
Published: October 2024

AbstractAmong the common strategies to design next-generation COVID-19 vaccines is broadening the antigenic repertoire thereby aiming to increase efficacy against emerging variants of concern (VoC). This study describes a new Orf virus-based vector (ORFV) platform to design a multiantigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Vaccine candidates were engineered, either expressing spike protein (ORFV-S) alone or co-expressing nucleocapsid protein (ORFV-S/N). Mono- and multiantigenic vaccines elicited comparable levels of spike-specific antibodies and virus neutralization in mice. Results from a SARS-CoV-2 challenge model in hamsters suggest cross-protective properties of the multiantigenic vaccine against VoC, indicating improved viral clearance with ORFV-S/N, as compared to equal doses of ORFV-S. In a nonhuman primate challenge model, vaccination with the ORFV-S/N vaccine resulted in long-term protection against SARS-CoV-2 infection. These results demonstrate the potential of the ORFV platform for prophylactic vaccination and represent a preclinical development program supporting first-in-man studies with the multiantigenic ORFV vaccine.
Efficient conversion of syngas to linear α-olefins by phase-pure χ-Fe5C2
Authors: Wang Peng , Chiang Fu-Kuo , Chai Jiachun , Dugulan A. Iulian , Dong Juan , Chen Wei , Broos Robin J. P. , Feng Bo , Song Yuanjun , Lv Yijun , Lin Quan , Wang Rongming , Filot Ivo A. W. , Men Zhuowu , Hensen Emiel J. M. 
Published: October 2024

AbstractOil has long been the dominant feedstock for producing fuels and chemicals, but coal, natural gas and biomass are increasingly explored alternatives1–3. Their conversion first generates syngas, a mixture of CO and H2, which is then processed further using Fischer–Tropsch (FT) chemistry. However, although commercial FT technology for fuel production is established, using it to access valuable chemicals remains challenging. A case in point is linear α-olefins (LAOs), which are important chemical intermediates obtained by ethylene oligomerization at present4–8. The commercial high-temperature FT process and the FT-to-olefin process under development at present both convert syngas directly to LAOs, but also generate much CO2 waste that leads to a low carbon utilization efficiency9–14. The efficiency is further compromised by substantially fewer of the converted carbon atoms ending up as valuable C5–C10 LAOs than are found in the C2–C4 olefins that dominate the product mixtures9–14. Here we show that the use of the original phase-pure χ-iron carbide can minimize these syngas conversion problems: tailored and optimized for the process of FT to LAOs, this catalyst exhibits an activity at 290 °C that is 1–2 orders higher than dedicated FT-to-olefin catalysts can achieve above 320 °C (refs. 12–15), is stable for 200 h, and produces desired C2–C10 LAOs and unwanted CO2 with carbon-based selectivities of 51% and 9% under industrially relevant conditions. This higher catalytic performance, persisting over a wide temperature range (250–320 °C), demonstrates the potential of the system for developing a practically relevant technology.
Global profiling of protein complex dynamics with an experimental library of protein interaction markers
Authors: Dörig Christian , Marulli Cathy , Peskett Thomas , Volkmar Norbert , Pantolini Lorenzo , Studer Gabriel , Paleari Camilla , Frommelt Fabian , Schwede Torsten , de Souza Natalie , Barral Yves , Picotti Paola 
Published: October 2024

AbstractMethods to systematically monitor protein complex dynamics are needed. We introduce serial ultrafiltration combined with limited proteolysis-coupled mass spectrometry (FLiP–MS), a structural proteomics workflow that generates a library of peptide markers specific to changes in PPIs by probing differences in protease susceptibility between complex-bound and monomeric forms of proteins. The library includes markers mapping to protein-binding interfaces and markers reporting on structural changes that accompany PPI changes. Integrating the marker library with LiP–MS data allows for global profiling of protein–protein interactions (PPIs) from unfractionated lysates. We apply FLiP–MS to Saccharomyces cerevisiae and probe changes in protein complex dynamics after DNA replication stress, identifying links between Spt-Ada-Gcn5 acetyltransferase activity and the assembly state of several complexes. FLiP–MS enables protein complex dynamics to be probed on any perturbation, proteome-wide, at high throughput, with peptide-level structural resolution and informing on occupancy of binding interfaces, thus providing both global and molecular views of a system under study.
Rastermap: a discovery method for neural population recordings
Authors: Stringer Carsen , Zhong Lin , Syeda Atika , Du Fengtong , Kesa Maria , Pachitariu Marius 
Published: October 2024

AbstractNeurophysiology has long progressed through exploratory experiments and chance discoveries. Anecdotes abound of researchers listening to spikes in real time and noticing patterns of activity related to ongoing stimuli or behaviors. With the advent of large-scale recordings, such close observation of data has become difficult. To find patterns in large-scale neural data, we developed ‘Rastermap’, a visualization method that displays neurons as a raster plot after sorting them along a one-dimensional axis based on their activity patterns. We benchmarked Rastermap on realistic simulations and then used it to explore recordings of tens of thousands of neurons from mouse cortex during spontaneous, stimulus-evoked and task-evoked epochs. We also applied Rastermap to whole-brain zebrafish recordings; to wide-field imaging data; to electrophysiological recordings in rat hippocampus, monkey frontal cortex and various cortical and subcortical regions in mice; and to artificial neural networks. Finally, we illustrate high-dimensional scenarios where Rastermap and similar algorithms cannot be used effectively.
Enhancing diffusion-weighted prostate MRI through self-supervised denoising and evaluation
Authors: Pfaff Laura , Darwish Omar , Wagner Fabian , Thies Mareike , Vysotskaya Nastassia , Hossbach Julian , Weiland Elisabeth , Benkert Thomas , Eichner Cornelius , Nickel Dominik , Wuerfl Tobias , Maier Andreas 
Published: October 2024

AbstractDiffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that provides information about the Brownian motion of water molecules within biological tissues. DWI plays a crucial role in stroke imaging and oncology, but its diagnostic value can be compromised by the inherently low signal-to-noise ratio (SNR). Conventional supervised deep learning-based denoising techniques encounter challenges in this domain as they necessitate noise-free target images for training. This work presents a novel approach for denoising and evaluating DWI scans in a self-supervised manner, eliminating the need for ground-truth data. By leveraging an adapted version of Stein’s unbiased risk estimator (SURE) and exploiting a phase-corrected combination of repeated acquisitions, we outperform both state-of-the-art self-supervised denoising methods and conventional non-learning-based approaches. Additionally, we demonstrate the applicability of our proposed approach in accelerating DWI scans by acquiring fewer image repetitions. To evaluate denoising performance, we introduce a self-supervised methodology that relies on analyzing the characteristics of the residual signal removed by the denoising approaches.
Structure of endothelin ETB receptor–Gi complex in a conformation stabilized by unique NPxxL motif
Authors: Tani Kazutoshi , Maki-Yonekura Saori , Kanno Ryo , Negami Tatsuki , Hamaguchi Tasuku , Hall Malgorzata , Mizoguchi Akira , Humbel Bruno M. , Terada Tohru , Yonekura Koji , Doi Tomoko 
Published: October 2024

AbstractEndothelin type B receptor (ETBR) plays a crucial role in regulating blood pressure and humoral homeostasis, making it an important therapeutic target for related diseases. ETBR activation by the endogenous peptide hormones endothelin (ET)−1–3 stimulates several signaling pathways, including Gs, Gi/o, Gq/11, G12/13, and β-arrestin. Although the conserved NPxxY motif in transmembrane helix 7 (TM7) is important during GPCR activation, ETBR possesses the lesser known NPxxL motif. In this study, we present the cryo-EM structure of the ETBR–Gi complex, complemented by MD simulations and functional studies. These investigations reveal an unusual movement of TM7 to the intracellular side during ETBR activation and the essential roles of the diverse NPxxL motif in stabilizing the active conformation of ETBR and organizing the assembly of the binding pocket for the α5 helix of Gi protein. These findings enhance our understanding of the interactions between GPCRs and G proteins, thereby advancing the development of therapeutic strategies.
Patterns of (micro)nutrient limitation across the South Pacific Ocean
Authors: Liu Haoran , Yuan Zhongwei , Gosnell Kathleen J. , Liu Te , Tammen Juliane K. , Wen Zuozhu , Engel Anja , Liu Xin , Huang Bangqin , Kao Shuh‐Ji , Achterberg Eric P. , Browning Thomas J. 
Published: October 2024

AbstractNutrient limitation regulates phytoplankton growth throughout much of the global ocean and its assessment is important for our understanding of future changes in ocean productivity. The South Pacific Ocean represents a vast region where limiting nutrients have so far been investigated with only a handful of experiments. Here we report the results of eleven nutrient addition bioassay experiments conducted across the South Pacific Ocean at ca. 30°S as part of the GEOTRACES GP21 expedition. Nitrogen addition alone stimulated chlorophyll-a accumulation at all sites, whilst increases were larger following supplementary addition of iron in the eastern and central basin, and phosphate in the western basin. Enhanced iron stress following nitrogen addition in the eastern and central basin further pointed towards ambient iron concentrations approaching co-limiting levels. The overall east-to-west shift in serial limiting nutrients from iron to phosphate was attributed to a broadscale east-west increase in iron availability relative to nitrogen.
Activity, structure, and diversity of Type II proline-rich antimicrobial peptides from insects
Authors: Huang Weiping , Baliga Chetana , Aleksandrova Elena V , Atkinson Gemma , Polikanov Yury S , Vázquez-Laslop Nora , Mankin Alexander S 
Published: October 2024

AbstractApidaecin 1b (Api), the first characterized Type II Proline-rich antimicrobial peptide (PrAMP), is encoded in the honey bee genome. It inhibits bacterial growth by binding in the nascent peptide exit tunnel of the ribosome after the release of the completed protein and trapping the release factors. By genome mining, we have identified 71 PrAMPs encoded in insect genomes as pre-pro-polyproteins. Having chemically synthesized and tested the activity of 26 peptides, we demonstrate that despite significant sequence variation in the N-terminal sequence, the majority of the PrAMPs that retain the conserved C-terminal sequence of Api are able to trap the ribosome at the stop codons and induce stop codon readthrough—all hallmarks of Type II PrAMP mode of action. Some of the characterized PrAMPs exhibit superior antibacterial activity in comparison with Api. The newly solved crystallographic structures of the ribosome complexed with Api and with the more active peptide Fva1 from the stingless bee demonstrate the universal placement of the PrAMPs’ C-terminal pharmacophore in the post-release ribosome despite variations in their N-terminal sequence.