bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of the Complexity of a Finite Mixture Distribution: From Well- to Less Known Methods
Authors: Balabdaoui Fadoua , Kolar Andrei , Kulagina Yulia , Müller Lilian 
Published: August 2022

AbstractMixture models occur in numerous settings including random and fixed effects models, clustering, deconvolution, empirical Bayes problems and many others. They are often used to model data originating from a heterogeneous population, consisting of several homogeneous subpopulations, and the problem of finding a good estimator for the number of components in the mixture arises naturally. Estimation of the order of a finite mixture model is a hard statistical task, and multiple techniques have been suggested for solving it. We will concentrate on several methods that have not gained much popularity yet deserve the attention of practitioners. These can be categorized into three groups: tools built upon the determinant of the Hankel matrix of moments of the mixing distribution, minimum distance estimators, likelihood ratio tests. We will address theoretical pillars underlying each of the methods, provide some useful modifications for enhancing their performance and present the results of the comparative numerical study that has been conducted under various scenarios. According to the results, none of the methods proves to be a “magic pill”. The results uncover limitations of the techniques and provide practical hints for choosing the best-suited tool under specific conditions.
Feasibility, impact, and priority of key strategies to enhance diverse and inclusive training programs in clinical and translational research: A mixed methods study
Authors: Campbell Jennifer A. , Walker Rebekah J. , Dawson Aprill Z. , Ozieh Mukoso N. , Schmidt Susanne , Shay L. Aubree , Williams Joni S. , Phillips Shane A. , Egede Leonard E. 
Published: August 2022

Abstract

Background:
Enhancing diversity in the scientific workforce is a long-standing issue. This study uses mixed methods to understand the feasibility, impact, and priority of six key strategies to promote diverse and inclusive training and contextualize the six key strategies across Clinical and Translational Science Awards (CTSAs) Program Institutions.

Methods:
Four breakout sessions were held at the NCATS 2020 CTSA Program annual meeting focused on diversity, equity, and inclusion (DEI) efforts. This paper focuses on the breakout session for Enhancing DEI in Translational Science Training Programs. Data were analyzed using a mixed methods convergent approach. The quantitative strand includes the online polling results. The qualitative strand includes the breakout session and the chat box in response to the training presentation.

Results:
Across feasibility, impact, and priority questions, prioritizing representation ranked number 1. Building partnerships ranked number 2 in feasibility and priority, while making it personal ranked number 2 for impact. Across each strategy, rankings supported the qualitative data findings in feasibility through shared experiences, impact in the ability to increase DEI, and priority rankings in comparison to the other strategies. No divergence was found across quantitative and qualitative data findings.

Conclusion:
Findings provide robust support for prioritizing representation as a number one strategy to focus on in training programs. Specifically, this strategy can be operationalized through integration of community representation, diversity advocates, and adopting a holistic approach to recruiting a diverse cadre of scholars into translational science training programs at the national level across CTSAs.
The moments of the time of ruin in Sparre Andersen risk models
Authors: Dickson David C.M. 
Published: August 2022

AbstractWe derive formulae for the moments of the time of ruin in both ordinary and modified Sparre Andersen risk models without specifying either the inter-claim time distribution or the individual claim amount distribution. We illustrate the application of our results in the special case of exponentially distributed claims, as well as for the following ordinary models: the classical risk model, phase-type(2) risk models, and the Erlang(
$\mathscr{n}$
) risk model. We also show how the key quantities for modified models can be found.
Hippocampal circuit dysfunction in psychosis
Authors: Knight Samuel , McCutcheon Robert , Dwir Daniella , Grace Anthony A. , O’Daly Owen , McGuire Philip , Modinos Gemma 
Published: August 2022

AbstractDespite strong evidence of the neurodevelopmental origins of psychosis, current pharmacological treatment is not usually initiated until after a clinical diagnosis is made, and is focussed on antagonising striatal dopamine receptors. These drugs are only partially effective, have serious side effects, fail to alleviate the negative and cognitive symptoms of the disorder, and are not useful as a preventive treatment. In recent years, attention has turned to upstream brain regions that regulate striatal dopamine function, such as the hippocampus. This review draws together these recent data to discuss why the hippocampus may be especially vulnerable in the pathophysiology of psychosis. First, we describe the neurodevelopmental trajectory of the hippocampus and its susceptibility to dysfunction, exploring this region’s proneness to structural and functional imbalances, metabolic pressures, and oxidative stress. We then examine mechanisms of hippocampal dysfunction in psychosis and in individuals at high-risk for psychosis and discuss how and when hippocampal abnormalities may be targeted in these groups. We conclude with future directions for prospective studies to unlock the discovery of novel therapeutic strategies targeting hippocampal circuit imbalances to prevent or delay the onset of psychosis.
LncRNA HEPFAL accelerates ferroptosis in hepatocellular carcinoma by regulating SLC7A11 ubiquitination
Authors: Zhang Baofu , Bao Wenming , Zhang Sina , Chen Bo , Zhou Xiang , Zhao Jungang , Shi Zhehao , Zhang Tan , Chen Ziyan , Wang Luhui , Zheng Xiangtao , Chen Gang , Wang Yi 
Published: August 2022

AbstractFerroptosis is a new type of cell death that has been recognized in recent years and is different from apoptosis, autophagy, and necrosis. It is mainly due to cellular iron homeostasis and lipid peroxidation of iron metabolism caused by large accumulation. There is a close correlation between ferroptosis and hepatocellular carcinoma (HCC). This study shows that the expression of the long noncoding RNA HEPFAL was reduced in HCC tissues. We found that lncRNA HEPFAL can promote ferroptosis by reducing the expression of solute carrier family 7 member 11 (SLC7A11) and increasing the levels of lipid reactive oxygen species (ROS) and iron (two surrogate markers of ferroptosis). In addition, we found that lncRNA HEPFAL increases the sensitivity of erastin-induced ferroptosis, which may be related to mTORC1, and lncRNA HEPFAL can promote the ubiquitination of SLC7A11 and reduce the stability of the SLC7A11 protein, resulting in decreased expression. Understanding these mechanisms indicates that lncRNAs related to ferroptosis are essential for the occurrence and treatment of HCC.
Self-cycled photo-Fenton-like system based on an artificial leaf with a solar-to-H2O2 conversion efficiency of 1.46%
Authors: Dong Chaoran , Yang Yilong , Hu Xuemin , Cho Yoonjun , Jang Gyuyong , Ao Yanhui , Wang Luyang , Shen Jinyou , Park Jong Hyeok , Zhang Kan 
Published: August 2022

AbstractMillions of families around the world remain vulnerable to water scarcity and have no access to drinking water. Advanced oxidation processes (AOPs) are an effective way towards water purification with qualified reactive oxygen species (ROSs) while are impeded by the high-cost and tedious process in either input of consumable reagent, production of ROSs, and the pre-treatment of supporting electrolyte. Herein, we couple solar light-assisted H2O2 production from water and photo-Fenton-like reactions into a self-cyclable system by using an artificial leaf, achieving an unassisted H2O2 production rate of 0.77 μmol/(min·cm2) under 1 Sun AM 1.5 illumination. Furthermore, a large (70 cm2) artificial leaf was used for an unassisted solar-driven bicarbonate-activated hydrogen peroxide (BAP) system with recycled catalysts for real-time wastewater purification with requirements for only water, oxygen and sunlight. This demonstration highlights the feasibility and scalability of photoelectrochemical technology for decentralized environmental governance applications from laboratory benchtops to industry.
Convergence in phosphorus constraints to photosynthesis in forests around the world
Authors: Ellsworth David S. , Crous Kristine Y. , De Kauwe Martin G. , Verryckt Lore T. , Goll Daniel , Zaehle Sönke , Bloomfield Keith J. , Ciais Philippe , Cernusak Lucas A. , Domingues Tomas F. , Dusenge Mirindi Eric , Garcia Sabrina , Guerrieri Rossella , Ishida F. Yoko , Janssens Ivan A. , Kenzo Tanaka , Ichie Tomoaki , Medlyn Belinda E. , Meir Patrick , Norby Richard J. , Reich Peter B. , Rowland Lucy , Santiago Louis S. , Sun Yan , Uddling Johan , Walker Anthony P. , Weerasinghe K. W. Lasantha K. , van de Weg Martine J. , Zhang Yun-Bing , Zhang Jiao-Lin , Wright Ian J. 
Published: August 2022

AbstractTropical forests take up more carbon (C) from the atmosphere per annum by photosynthesis than any other type of vegetation. Phosphorus (P) limitations to C uptake are paramount for tropical and subtropical forests around the globe. Yet the generality of photosynthesis-P relationships underlying these limitations are in question, and hence are not represented well in terrestrial biosphere models. Here we demonstrate the dependence of photosynthesis and underlying processes on both leaf N and P concentrations. The regulation of photosynthetic capacity by P was similar across four continents. Implementing P constraints in the ORCHIDEE-CNP model, gross photosynthesis was reduced by 36% across the tropics and subtropics relative to traditional N constraints and unlimiting leaf P. Our results provide a quantitative relationship for the P dependence for photosynthesis for the front-end of global terrestrial C models that is consistent with canopy leaf measurements.
In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions
Authors: Nicolas Clara T. , VanLith Caitlin J. , Hickey Raymond D. , Du Zeji , Hillin Lori G. , Guthman Rebekah M. , Cao William J. , Haugo Benjamin , Lillegard Annika , Roy Diya , Bhagwate Aditya , O’Brien Daniel , Kocher Jean-Pierre , Kaiser Robert A. , Russell Stephen J. , Lillegard Joseph B. 
Published: August 2022

AbstractConventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)−1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression to liver fibrosis, liver failure, and activation of tumorigenic pathways. Here we demonstrate cure of HT1 by direct, in vivo administration of a therapeutic lentiviral vector targeting the expression of a human fumarylacetoacetate hydrolase (FAH) transgene in the porcine model of HT1. This therapy is well tolerated and provides stable long-term expression of FAH in pigs with HT1. Genomic integration displays a benign profile, with subsequent fibrosis and tumorigenicity gene expression patterns similar to wild-type animals as compared to NTBC-treated or diseased untreated animals. Indeed, the phenotypic and genomic data following in vivo lentiviral vector administration demonstrate comparative superiority over other therapies including ex vivo cell therapy and therefore support clinical application of this approach.
Current Siberian heating is unprecedented during the past seven millennia
Authors: Hantemirov Rashit M. , Corona Christophe , Guillet Sébastien , Shiyatov Stepan G. , Stoffel Markus , Osborn Timothy J. , Melvin Thomas M. , Gorlanova Ludmila A. , Kukarskih Vladimir V. , Surkov Alexander Y. , von Arx Georg , Fonti Patrick 
Published: August 2022

AbstractThe Arctic is warming faster than any other region on Earth. Putting this rapid warming into perspective is challenging because instrumental records are often short or incomplete in polar regions and precisely-dated temperature proxies with high temporal resolution are largely lacking. Here, we provide this long-term perspective by reconstructing past summer temperature variability at Yamal Peninsula – a hotspot of recent warming – over the past 7638 years using annually resolved tree-ring records. We demonstrate that the recent anthropogenic warming interrupted a multi-millennial cooling trend. We find the industrial-era warming to be unprecedented in rate and to have elevated the summer temperature to levels above those reconstructed for the past seven millennia (in both 30-year mean and the frequency of extreme summers). This is undoubtedly of concern for the natural and human systems that are being impacted by climatic changes that lie outside the envelope of natural climatic variations for this region.
Towards critical white ice conditions in lakes under global warming
Authors: Weyhenmeyer Gesa A. , Obertegger Ulrike , Rudebeck Hugo , Jakobsson Ellinor , Jansen Joachim , Zdorovennova Galina , Bansal Sheel , Block Benjamin D. , Carey Cayelan C. , Doubek Jonathan P. , Dugan Hilary , Erina Oxana , Fedorova Irina , Fischer Janet M. , Grinberga Laura , Grossart Hans-Peter , Kangur Külli , Knoll Lesley B. , Laas Alo , Lepori Fabio , Meier Jacob , Palshin Nikolai , Peternell Mark , Pulkkanen Merja , Rusak James A. , Sharma Sapna , Wain Danielle , Zdorovennov Roman 
Published: August 2022

AbstractThe quality of lake ice is of uppermost importance for ice safety and under-ice ecology, but its temporal and spatial variability is largely unknown. Here we conducted a coordinated lake ice quality sampling campaign across the Northern Hemisphere during one of the warmest winters since 1880 and show that lake ice during 2020/2021 commonly consisted of unstable white ice, at times contributing up to 100% to the total ice thickness. We observed that white ice increased over the winter season, becoming thickest and constituting the largest proportion of the ice layer towards the end of the ice cover season when fatal winter drownings occur most often and light limits the growth and reproduction of primary producers. We attribute the dominance of white ice before ice-off to air temperatures varying around the freezing point, a condition which occurs more frequently during warmer winters. Thus, under continued global warming, the prevalence of white ice is likely to substantially increase during the critical period before ice-off, for which we adjusted commonly used equations for human ice safety and light transmittance through ice.
Specificity of TGF-β1 signal designated by LRRC33 and integrin αVβ8
Authors: Duan Zelin , Lin Xuezhen , Wang Lixia , Zhen Qiuxin , Jiang Yuefeng , Chen Chuxin , Yang Jing , Lee Chia-Hsueh , Qin Yan , Li Ying , Zhao Bo , Wang Jianchuan , Zhang Zhe 
Published: August 2022

AbstractMyeloid lineage cells present the latent form of transforming growth factor-β1 (L-TGF-β1) to the membrane using an anchor protein LRRC33. Integrin αVβ8 activates extracellular L-TGF-β1 to trigger the downstream signaling functions. However, the mechanism designating the specificity of TGF-β1 presentation and activation remains incompletely understood. Here, we report cryo-EM structures of human L-TGF-β1/LRRC33 and integrin αVβ8/L-TGF-β1 complexes. Combined with biochemical and cell-based analyses, we demonstrate that LRRC33 only presents L-TGF-β1 but not the -β2 or -β3 isoforms due to difference of key residues on the growth factor domains. Moreover, we reveal a 2:2 binding mode of integrin αVβ8 and L-TGF-β1, which shows higher avidity and more efficient L-TGF-β1 activation than previously reported 1:2 binding mode. We also uncover that the disulfide-linked loop of the integrin subunit β8 determines its exquisite affinity to L-TGF-β1. Together, our findings provide important insights into the specificity of TGF-β1 signaling achieved by LRRC33 and integrin αVβ8.
CK2-induced cooperation of HHEX with the YAP-TEAD4 complex promotes colorectal tumorigenesis
Authors: Guo Yuegui , Zhu Zhehui , Huang Zhenyu , Cui Long , Yu Wei , Hong Wanjin , Zhou Zhaocai , Du Peng , Liu Chen-Ying 
Published: August 2022

AbstractDysregulation of Hippo pathway leads to hyperactivation of YAP-TEAD transcriptional complex in various cancers, including colorectal cancer (CRC). In this study, we observed that HHEX (Hematopoietically expressed homeobox) may enhance transcription activity of the YAP-TEAD complex. HHEX associates with and stabilizes the YAP-TEAD complex on the regulatory genomic loci to coregulate the expression of a group of YAP/TEAD target genes. Also, HHEX may indirectly regulate these target genes by controlling YAP/TAZ expression. Importantly, HHEX is required for the pro-tumorigenic effects of YAP during CRC progression. In response to serum stimulation, CK2 (Casein Kinase 2) phosphorylates HHEX and enhances its interaction with TEAD4. A CK2 inhibitor CX-4945 diminishes the interaction between HHEX and TEAD4, leading to decreased expression of YAP/TEAD target genes. CX-4945 synergizes the antitumor activity of YAP-TEAD inhibitors verteporfin and Super-TDU. Elevated expression of HHEX is correlated with hyperactivation of YAP/TEAD and associated with poor prognosis of CRC patients. Overall, our study identifies HHEX as a positive modulator of YAP/TEAD to promote colorectal tumorigenesis, providing a new therapeutic strategy for targeting YAP/TEAD in CRC.
Catalytic ozone decomposition and adsorptive VOCs removal in bimetallic metal-organic frameworks
Authors: Dong Chen , Yang Jia-Jia , Xie Lin-Hua , Cui Ganglong , Fang Wei-Hai , Li Jian-Rong 
Published: August 2022

AbstractAtmospheric ozone has long been a threat to human health, however, rational design of high-performance O3-decomposition catalysts remains challenging. Herein, we demonstrate the great potential of a series of isomorphous bimetallic MOFs denoted as PCN-250(Fe2M) (M = Co2+, Ni2+, Mn2+) in catalytic O3 decomposition. Particularly, PCN-250(Fe2Co) showed 100% O3 removal efficiency for a continuous air flow containing 1 ppm O3 over a wide humidity range (0 ‒ 80% RH) at room temperature. Mechanism studies suggested that the high catalytic performance originated from the introduction of open Co(II) sites as well as its porous structure. Additionally, at low pressures around 10 Pa, PCN-250(Fe2Co) exhibited high adsorption capacities (89 ‒ 241 mg g−1) for most VOCs, which are not only a class of hazardous air pollutants but also the precursor of O3. This work opens up a new avenue to develop advanced air purification materials for O3 and VOCs removal in one.
Single residue modulators of amyloid formation in the N-terminal P1-region of α-synuclein
Authors: Ulamec Sabine M. , Maya-Martinez Roberto , Byrd Emily J. , Dewison Katherine M. , Xu Yong , Willis Leon F. , Sobott Frank , Heath George R. , van Oosten Hawle Patricija , Buchman Vladimir L. , Radford Sheena E. , Brockwell David J. 
Published: August 2022

AbstractAlpha-synuclein (αSyn) is a protein involved in neurodegenerative disorders including Parkinson’s disease. Amyloid formation of αSyn can be modulated by the ‘P1 region’ (residues 36-42). Here, mutational studies of P1 reveal that Y39A and S42A extend the lag-phase of αSyn amyloid formation in vitro and rescue amyloid-associated cytotoxicity in C. elegans. Additionally, L38I αSyn forms amyloid fibrils more rapidly than WT, L38A has no effect, but L38M does not form amyloid fibrils in vitro and protects from proteotoxicity. Swapping the sequence of the two residues that differ in the P1 region of the paralogue γSyn to those of αSyn did not enhance fibril formation for γSyn. Peptide binding experiments using NMR showed that P1 synergises with residues in the NAC and C-terminal regions to initiate aggregation. The remarkable specificity of the interactions that control αSyn amyloid formation, identifies this region as a potential target for therapeutics, despite their weak and transient nature.
Cellular taxonomy of Hic1+ mesenchymal progenitor derivatives in the limb: from embryo to adult
Authors: Arostegui Martin , Scott R. Wilder , Böse Kerstin , Underhill T. Michael 
Published: August 2022

AbstractTissue development and regeneration rely on the cooperation of multiple mesenchymal progenitor (MP) subpopulations. We recently identified Hic1 as a marker of quiescent MPs in multiple adult tissues. Here, we describe the embryonic origin of appendicular Hic1+ MPs and demonstrate that they arise in the hypaxial somite, and migrate into the developing limb at embryonic day 11.5, well after limb bud initiation. Time-resolved single-cell-omics analyses coupled with lineage tracing reveal that Hic1+ cells generate a unique MP hierarchy, that includes both recently identified adult universal fibroblast populations (Dpt+, Pi16+ and Dpt+Col15a1+) and more specialised mesenchymal derivatives such as, peri and endoneurial cells, pericytes, bone marrow stromal cells, myotenocytes, tenocytes, fascia-resident fibroblasts, with limited contributions to chondrocytes and osteocytes within the skeletal elements. MPs endure within these compartments, continue to express Hic1 and represent a critical reservoir to support post-natal growth and regeneration.
Arctic sea-ice loss is projected to lead to more frequent strong El Niño events
Authors: Liu Jiping , Song Mirong , Zhu Zhu , Horton Radley M. , Hu Yongyun , Xie Shang-Ping 
Published: August 2022

AbstractArctic sea ice has decreased substantially and is projected to reach a seasonally ice-free state in the coming decades. Little is known about whether dwindling Arctic sea ice is capable of influencing the occurrence of strong El Niño, a prominent mode of climate variability with global impacts. Based on time slice coupled model experiments, here we show that no significant change in the occurrence of strong El Niño is found in response to moderate Arctic sea-ice loss that is consistent with satellite observations to date. However, as the ice loss continues and the Arctic becomes seasonally ice-free, the frequency of strong El Niño events increases by more than one third, as defined by gradient-based indices that remove mean tropical Pacific warming induced by the seasonally ice-free Arctic. By comparing our time slice experiments with greenhouse warming experiments, we conclude that at least 37–48% of the increase of strong El Niño near the end of the 21st century is associated specifically with Arctic sea-ice loss. Further separation of Arctic sea-ice loss and greenhouse gas forcing only experiments implies that the seasonally ice-free Arctic might play a key role in driving significantly more frequent strong El Niño events.
Thiol-Yne click chemistry of acetylene-enabled macrocyclization
Authors: Lü Shiwei , Wang Zipeng , Zhu Shifa 
Published: August 2022

AbstractMacrocycles have fascinated scientists for over half a century due to their aesthetically appealing structures and broad utilities in chemical, material, and biological research. However, the efficient preparation of macrocycles remains an ongoing research challenge in organic synthesis because of the high entropic penalty involved in the ring-closing process. Herein we report a photocatalyzed thiol-yne click reaction to forge diverse sulfur-containing macrocycles (up to 35-membered ring) and linear C2-linked 1,2-(S-S/S-P/S-N) functionalized molecules, starting from the simplest alkyne, acetylene. Preliminary mechanistic experiments support a visible light-mediated radical-polar crossover dihydrothiolation process. This operationally straightforward reaction is also amenable to the synthesis of organometallic complexes, bis-sulfoxide ligand and a pleuromutilin antibiotic drug Tiamulin, which provides a practical route to synthesize highly valued compounds from the feedstock acetylene gas.