bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why were there no war crimes trials for the Korean War?
Authors: Wilson Sandra 
Published: May 2021

AbstractIn the Korean War of 1950-53, U.S. authorities were determined to pursue atrocities perpetrated by North Korean and Communist Chinese forces through legal channels, in keeping with the standards they believed they had set after the Second World War. Yet, their plans foundered in Korea, despite extensive groundwork for prosecutions. Four factors were responsible. First, it was difficult to find reliable evidence and to identify and apprehend suspects. Second, U.S. officials rapidly lost confidence in the idea of prosecuting national leaders. Third, the lack of clear-cut victory in the conflict necessitated a diplomatic solution, which was incompatible with war crimes trials. Fourth, the moral standing of the West, and hence its authority to run trials, was undermined by the large number of atrocities committed by the United Nations side. Thus, the U.S. plan for war crimes trials was dropped without fanfare, to be replaced by an anti-Communist propaganda campaign.
Heat Flux From a Vapor‐Dominated Hydrothermal Field Beneath Yellowstone Lake
Authors: Favorito Julia E. , Harris Robert N. , Sohn Robert A. , Hurwitz Shaul , Luttrell Karen M. 
Published: May 2021

AbstractWe report results from 149 heat flux measurements made over an ∼2‐year interval at sites in and around a vapor‐dominated geothermal field located at water depths of ∼100–120 m in Yellowstone Lake, Wyoming. Measurements of both in situ temperature and thermal conductivity as a function of depth were made with a 1 m probe via a remotely operated vehicle, and are combined to compute the vertical conductive heat flux. Inside the ∼55.5 × 103 m2 bathymetric depression demarcating the vapor‐dominated field, the median conductive flux is 13 W m−2, with a conductive output of 0.72 MW. Outside the thermal field, the median conductive flux is 3.5 W m−2. We observed 49 active vents inside the thermal field, with an estimated mass discharge rate of 56 kg s−1, a median exit‐fluid temperature of 132°C, and a total heat output of 29 MW. We find evidence for relatively weak secondary convection with a total output of 0.09 MW in thermal area lake floor sediments. Our data indicate that vapor beneath the thermal field is trapped by a low‐permeability cap at a temperature of ∼189°C and a depth of ∼15 m below the lake floor. The thermal output of the Deep Hole is among the highest of any vapor‐dominated field in Yellowstone, due in part to the high boiling temperatures associated with the elevated lake floor pressures.
Eastward‐Propagating Planetary Waves Prior to the January 2009 Sudden Stratospheric Warming
Authors: Rhodes Christian T. , Limpasuvan Varavut , Orsolini Yvan J. 
Published: May 2021

AbstractEastward‐propagating planetary waves (EPWs) were investigated prior to the boreal January 2009 major sudden stratospheric warming (SSW) event simulated by the National Center for Atmospheric Research's Whole Atmosphere Community Climate Model with specified dynamics. About 22 days before SSW onset, a background flow with jet maxima around the upper polar stratosphere and subtropical mesosphere developed due to the net forcing by gravity and planetary waves. The mesospheric wind structure was largely unstable and supported a wave geometry conducive to overreflection. With a zonal phase speed of ∼10 m s−1, EPWs appeared near their turning and critical layers as wavenumber‐2 perturbations in the stratosphere and mesosphere. Accompanied by upward EPW activity from the lower stratosphere, EPW growth exhibited characteristics of wave instability and overreflection.
Role of Surface Gravity Waves in Aquaplanet Ocean Climates
Authors: Studholme Joshua H. P. , Markina Margarita Y. , Gulev Sergey K. 
Published: May 2021

AbstractWe present a set of idealized numerical experiments of a solstitial aquaplanet ocean and examine the thermodynamic and dynamic implications of surface gravity waves (SGWs) upon its mean state. The aquaplanet's oceanic circulation is dominated by an equatorial zonal jet and four Ekman driven meridional overturning circulation (MOC) cells aligned with the westerly atmospheric jet streams and easterly trade winds in both hemispheres. Including SGW parameterization (representing modulations of air‐sea momentum fluxes, Langmuir circulation, and Stokes‐Coriolis force) increases mixed layer vertical momentum diffusivity by ∼40% and dampens surface momentum fluxes by ∼4%. The correspondingly dampened MOC impacts the oceanic density structure to 1 km depth by lessening the large‐scale advective transports of heat and salt, freshening the equatorial latitudes (where evaporation minus precipitation [E − P] is negative) and increasing salinity in the subtropics (where E − P is positive) by ∼1%. The midlatitude pycnocline in both hemispheres is deepened by the inclusion of SGWs. Including SGWs into the aquaplanet ocean model acts to increase mixed layer depth by ∼10% (up to 20% in the wintertime in midlatitudes), decrease vertical shear in the upper 200 m and alter local midlatitude buoyancy frequency. Generally, the impacts of SGWs upon the aquaplanet ocean are found to be consistent across cooler and warmer climates. We suggest that the implications of these simulations could be relevant to understanding future projections of SGW climate, exoplanetary oceans, and the dynamics of the Southern Ocean mixed layer.
A Vector‐Based River Routing Model for Earth System Models: Parallelization and Global Applications
Authors: Mizukami Naoki , Clark Martyn P. , Gharari Shervan , Kluzek Erik , Pan Ming , Lin Peirong , Beck Hylke E. , Yamazaki Dai 
Published: May 2021

AbstractA vector‐river network explicitly uses realistic geometries of river reaches and catchments for spatial discretization in a river model. This enables improving the accuracy of the physical properties of the modeled river system, compared to a gridded river network that has been used in Earth System Models. With a finer‐scale river network, resolving smaller‐scale river reaches, there is a need for efficient methods to route streamflow and its constituents throughout the river network. The purpose of this study is twofold: (1) develop a new method to decompose river networks into hydrologically independent tributary domains, where routing computations can be performed in parallel; and (2) perform global river routing simulations with two global river networks, with different scales, to examine the computational efficiency and the differences in discharge simulations at various temporal scales. The new parallelization method uses a hierarchical decomposition strategy, where each decomposed tributary is further decomposed into many sub‐tributary domains, enabling hybrid parallel computing. This parallelization scheme has excellent computational scaling for the global domain where it is straightforward to distribute computations across many independent river basins. However, parallel computing for a single large basin remains challenging. The global routing experiments show that the scale of the vector‐river network has less impact on the discharge simulations than the runoff input that is generated by the combination of land surface model and meteorological forcing. The scale of vector‐river networks needs to consider the scale of local hydrologic features such as lakes that are to be resolved in the network.
The arachidonic acid metabolite 11,12-epoxyeicosatrienoic acid alleviates pulmonary fibrosis
Authors: Kim Hak Su , Moon Su-Jin , Lee Sang Eun , Hwang Gi Won , Yoo Hyun Ju , Song Jin Woo 
Published: May 2021

AbstractEpoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that are rapidly metabolized into diols by soluble epoxide hydrolase (sEH). sEH inhibition has been shown to increase the biological activity of EETs, which are known to have anti-inflammatory properties. However, the role of EETs in pulmonary fibrosis remains unexplored. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze EETs in the lung tissues of patients with idiopathic pulmonary fibrosis (IPF, n = 29) and controls (n = 15), and the function of 11,12-EET was evaluated in in vitro and in vivo in pulmonary fibrosis models. EET levels in IPF lung tissues, including those of 8,9-EET, 11,12-EET, and 14,15-EET, were significantly lower than those in control tissues. The 11,12-EET/11,12-DHET ratio in human lung tissues also differentiated IPF from control tissues. 11,12-EET significantly decreased transforming growth factor (TGF)-β1-induced expression of α-smooth muscle actin (SMA) and collagen type-I in MRC-5 cells and primary fibroblasts from IPF patients. sEH-specific siRNA and 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU; sEH inhibitor) also decreased TGF-β1-induced expression of α-SMA and collagen type-I in fibroblasts. Moreover, 11,12-EET and TPPU decreased TGF-β1-induced p-Smad2/3 and extracellular-signal-regulated kinase (ERK) expression in primary fibroblasts from patients with IPF and fibronectin expression in Beas-2B cells. TPPU decreased the levels of hydroxyproline in the lungs of bleomycin-induced mice. 11,12-EET or sEH inhibitors could inhibit pulmonary fibrosis by regulating TGF-β1-induced profibrotic signaling, suggesting that 11,12-EET and the regulation of EETs could serve as potential therapeutic targets for IPF treatment.
Application of 3D bioprinting in the prevention and the therapy for human diseases
Authors: Yi Hee-Gyeong , Kim Hyeonji , Kwon Junyoung , Choi Yeong-Jin , Jang Jinah , Cho Dong-Woo 
Published: May 2021

AbstractRapid development of vaccines and therapeutics is necessary to tackle the emergence of new pathogens and infectious diseases. To speed up the drug discovery process, the conventional development pipeline can be retooled by introducing advanced in vitro models as alternatives to conventional infectious disease models and by employing advanced technology for the production of medicine and cell/drug delivery systems. In this regard, layer-by-layer construction with a 3D bioprinting system or other technologies provides a beneficial method for developing highly biomimetic and reliable in vitro models for infectious disease research. In addition, the high flexibility and versatility of 3D bioprinting offer advantages in the effective production of vaccines, therapeutics, and relevant delivery systems. Herein, we discuss the potential of 3D bioprinting technologies for the control of infectious diseases. We also suggest that 3D bioprinting in infectious disease research and drug development could be a significant platform technology for the rapid and automated production of tissue/organ models and medicines in the near future.
Bispecific antibody simultaneously targeting PD1 and HER2 inhibits tumor growth via direct tumor cell killing in combination with PD1/PDL1 blockade and HER2 inhibition
Authors: Gu Chang-ling , Zhu Hai-xia , Deng Lan , Meng Xiao-qing , Li Kai , Xu Wei , Zhao Le , Liu Yue-qin , Zhu Zhen-ping , Huang Hao-min 
Published: May 2021

AbstractImmune checkpoint blockade has shown significant clinical benefit in multiple cancer indications, but many patients are either refractory or become resistant to the treatment over time. HER2/neu oncogene overexpressed in invasive breast cancer patients associates with more aggressive diseases and poor prognosis. Anti-HER2 mAbs, such as trastuzumab, are currently the standard of care for HER2-overexpressing cancers, but the response rates are below 30% and patients generally suffer relapse within a year. In this study we developed a bispecific antibody (BsAb) simultaneously targeting both PD1 and HER2 in an attempt to combine HER2-targeted therapy with immune checkpoint blockade for treating HER2-positive solid tumors. The BsAb was constructed by fusing scFvs (anti-PD1) with the effector-functional Fc of an IgG (trastuzumab) via a flexible peptide linker. We showed that the BsAb bound to human HER2 and PD1 with high affinities (EC50 values were 0.2 and 0.14 nM, respectively), and exhibited potent antitumor activities in vitro and in vivo. Furthermore, we demonstrated that the BsAb exhibited both HER2 and PD1 blockade activities and was effective in killing HER2-positive tumor cells via antibody-dependent cellular cytotoxicity. In addition, the BsAb could crosslink HER2-positive tumor cells with T cells to form PD1 immunological synapses that directed tumor cell killing without the need of antigen presentation. Thus, the BsAb is a new promising approach for treating late-stage metastatic HER2-positive cancers.
STAT3/miR-135b/NF-κB axis confers aggressiveness and unfavorable prognosis in non-small-cell lung cancer
Authors: Zhao Jinlin , Wang Xin , Mi Zeyun , Jiang Xiangli , Sun Lin , Zheng Boyu , Wang Jing , Meng Maobin , Zhang Lu , Wang Zhongqiu , Song Junwei , Yuan Zhiyong , Wu Zhiqiang 
Published: May 2021

AbstractNon-small-cell lung cancer (NSCLC) is one of the most commonly diagnosed cancers worldwide but has limited effective therapies. Uncovering the underlying pathological and molecular changes, as well as mechanisms, will improve the treatment. Dysregulated microRNAs (miRNAs) have been proven to play important roles in the initiation and progression of various cancers, including NSCLC. In this manuscript, we identified microRNA-135b (miR-135b) as a tumor-promoting miRNA in NSCLC. We found that miR-135b was significantly upregulated and that its upregulation was associated with poor prognosis in NSCLC patients. miR-135b was an independent prognostic factor in NSCLC. Overexpressing miR-135b significantly promoted the aggressiveness of NSCLC, as evidenced by enhanced cell proliferation, migration, invasion, anti-apoptosis, and angiogenesis in vitro and in vivo, and knockdown of miR-135b had the opposite effects. Mechanistically, our results reveal that miR-135b directly targets the 3′-untranslated region (UTR) of the deubiquitinase CYLD, thereby modulating ubiquitination and activation of NF-κB signaling. Moreover, we found that interleukin-6 (IL-6)/STAT3 could elevate miR-135b levels and that STAT3 directly bound the promoter of miR-135b; thus, these findings highlight a new positive feedback loop of the IL-6/STAT3/miR-135b/NF-κB signaling in NSCLC and suggest that miR-135b could be a potential therapeutic target for NSCLC.
Therapeutic potential of targeting membrane-spanning proteoglycan SDC4 in hepatocellular carcinoma
Authors: Yang Heng , Liu Yang , Zhao Mei-Mei , Guo Qiang , Zheng Xi-Kang , Liu Dan , Zeng Ke-Wu , Tu Peng-Fei 
Published: May 2021

AbstractSyndecan-4 (SDC4) functions as a major endogenous membrane-associated receptor and widely regulates cytoskeleton, cell adhesion, and cell migration in human tumorigenesis and development, which represents a charming anti-cancer therapeutic target. Here, SDC4 was identified as a direct cellular target of small-molecule bufalin with anti-hepatocellular carcinoma (HCC) activity. Mechanism studies revealed that bufalin directly bond to SDC4 and selectively increased SDC4 interaction with substrate protein DEAD-box helicase 23 (DDX23) to induce HCC genomic instability. Meanwhile, pharmacological promotion of SDC4/DDX23 complex formation also inactivated matrix metalloproteinases (MMPs) and augmented p38/JNK MAPKs phosphorylation, which are highly associated with HCC proliferation and migration. Notably, specific knockdown of SDC4 or DDX23 markedly abolished bufalin-dependent inhibition of HCC proliferation and migration, indicating SDC4/DDX23 signaling axis is highly involved in the HCC process. Our results indicate that membrane-spanning proteoglycan SDC4 is a promising druggable target for HCC, and pharmacological regulation of SDC4/DDX23 signaling axis with small-molecule holds great potential to benefit HCC patients.
Monocytic MDSC mobilization promotes tumor recurrence after liver transplantation via CXCL10/TLR4/MMP14 signaling
Authors: Liu Hui , Ling Chang Chun , Yeung Wai Ho Oscar , Pang Li , Liu Jiang , Zhou Jie , Zhang Wei Yi , Liu Xiao Bing , Ng Tak Pan Kevin , Yang Xin Xiang , Lo Chung Mau , Man Kwan 
Published: May 2021

AbstractTumor recurrence is the major obstacle for pushing the envelope of liver transplantation for hepatocellular carcinoma (HCC) patients. The inflammatory cascades activated by acute liver graft injury promote tumor recurrence. We aimed to explore the role and mechanism of myeloid-derived suppressor cell (MDSC) mobilization induced by liver graft injury on tumor recurrence. By analyzing 331 HCC patients who received liver transplantation, the patients with graft weight ratio (GWR, the weight of liver graft divided by the estimated standard liver weight of recipient) <60% had higher tumor recurrence than GWR ≥60% ones. MDSCs and CXCL10/TLR4 levels were significantly increased in patients with GWR <60% or tumor recurrence. These findings were further validated in our rat orthotopic liver transplantation model. In CXCL10−/− and TLR4−/− mice of hepatic ischemia/reperfusion injury plus major hepatectomy (IRH) model, monocytic MDSCs, instead of granulocytic MDSCs, were significantly decreased. Importantly, CXCL10 deficiency reduced the accumulation of TLR4+ monocytic MDSCs, and CXCL10 increased MDSC mobilization in the presence of TLR4. Moreover, MMP14 was identified as the key molecule bridging CXCL10/TLR4 signaling and MDSC mobilization. Knockout or inhibition of CXCL10/TLR4 signaling significantly reduced the tumor growth with decreased monocytic MDSCs and MMP14 in the mouse tumor recurrent model. Our data indicated that monocytic MDSCs were mobilized and recruited to liver graft during acute phase injury, and to promote HCC recurrence after transplantation. Targeting MDSC mobilization via CXCL10/TLR4/MMP14 signaling may represent the therapeutic potential in decreasing post-transplant liver tumor recurrence.
Molecular mechanisms of ion conduction and ion selectivity in TMEM16 lipid scramblases
Authors: Kostritskii Andrei Y. , Machtens Jan-Philipp 
Published: May 2021

AbstractTMEM16 lipid scramblases transport lipids and also operate as ion channels with highly variable ion selectivities and various physiological functions. However, their molecular mechanisms of ion conduction and selectivity remain largely unknown. Using computational electrophysiology simulations at atomistic resolution, we identified the main ion-conductive state of TMEM16 lipid scramblases, in which an ion permeation pathway is lined by lipid headgroups that directly interact with permeating ions in a voltage polarity-dependent manner. We found that lipid headgroups modulate the ion-permeability state and regulate ion selectivity to varying degrees in different scramblase isoforms, depending on the amino-acid composition of the pores. Our work has defined the structural basis of ion conduction and selectivity in TMEM16 lipid scramblases and uncovered the mechanisms responsible for the direct effects of membrane lipids on the conduction properties of ion channels.
Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint
Authors: Schmidt Nathalie M. , Wing Peter A. C. , Diniz Mariana O. , Pallett Laura J. , Swadling Leo , Harris James M. , Burton Alice R. , Jeffery-Smith Anna , Zakeri Nekisa , Amin Oliver E. , Kucykowicz Stephanie , Heemskerk Mirjam H. , Davidson Brian , Meyer Tim , Grove Joe , Stauss Hans J. , Pineda-Torra Ines , Jolly Clare , Jury Elizabeth C. , McKeating Jane A. , Maini Mala K. 
Published: May 2021

AbstractDetermining divergent metabolic requirements of T cells, and the viruses and tumours they fail to combat, could provide new therapeutic checkpoints. Inhibition of acyl-CoA:cholesterol acyltransferase (ACAT) has direct anti-carcinogenic activity. Here, we show that ACAT inhibition has antiviral activity against hepatitis B (HBV), as well as boosting protective anti-HBV and anti-hepatocellular carcinoma (HCC) T cells. ACAT inhibition reduces CD8+ T cell neutral lipid droplets and promotes lipid microdomains, enhancing TCR signalling and TCR-independent bioenergetics. Dysfunctional HBV- and HCC-specific T cells are rescued by ACAT inhibitors directly ex vivo from human liver and tumour tissue respectively, including tissue-resident responses. ACAT inhibition enhances in vitro responsiveness of HBV-specific CD8+ T cells to PD-1 blockade and increases the functional avidity of TCR-gene-modified T cells. Finally, ACAT regulates HBV particle genesis in vitro, with inhibitors reducing both virions and subviral particles. Thus, ACAT inhibition provides a paradigm of a metabolic checkpoint able to constrain tumours and viruses but rescue exhausted T cells, rendering it an attractive therapeutic target for the functional cure of HBV and HBV-related HCC.
Marine snow morphology illuminates the evolution of phytoplankton blooms and determines their subsequent vertical export
Authors: Trudnowska Emilia , Lacour Léo , Ardyna Mathieu , Rogge Andreas , Irisson Jean Olivier , Waite Anya M. , Babin Marcel , Stemmann Lars 
Published: May 2021

AbstractThe organic carbon produced in the ocean’s surface by phytoplankton is either passed through the food web or exported to the ocean interior as marine snow. The rate and efficiency of such vertical export strongly depend on the size, structure and shape of individual particles, but apart from size, other morphological properties are still not quantitatively monitored. With the growing number of in situ imaging technologies, there is now a great possibility to analyze the morphology of individual marine snow. Thus, automated methods for their classification are urgently needed. Consequently, here we present a simple, objective categorization method of marine snow into a few ecologically meaningful functional morphotypes using field data from successive phases of the Arctic phytoplankton bloom. The proposed approach is a promising tool for future studies aiming to integrate the diversity, composition and morphology of marine snow into our understanding of the biological carbon pump.
Silica-copper catalyst interfaces enable carbon-carbon coupling towards ethylene electrosynthesis
Authors: Li Jun , Ozden Adnan , Wan Mingyu , Hu Yongfeng , Li Fengwang , Wang Yuhang , Zamani Reza R. , Ren Dan , Wang Ziyun , Xu Yi , Nam Dae-Hyun , Wicks Joshua , Chen Bin , Wang Xue , Luo Mingchuan , Graetzel Michael , Che Fanglin , Sargent Edward H. , Sinton David 
Published: May 2021

AbstractMembrane electrode assembly (MEA) electrolyzers offer a means to scale up CO2-to-ethylene electroconversion using renewable electricity and close the anthropogenic carbon cycle. To date, excessive CO2 coverage at the catalyst surface with limited active sites in MEA systems interferes with the carbon-carbon coupling reaction, diminishing ethylene production. With the aid of density functional theory calculations and spectroscopic analysis, here we report an oxide modulation strategy in which we introduce silica on Cu to create active Cu-SiOx interface sites, decreasing the formation energies of OCOH* and OCCOH*—key intermediates along the pathway to ethylene formation. We then synthesize the Cu-SiOx catalysts using one-pot coprecipitation and integrate the catalyst in a MEA electrolyzer. By tuning the CO2 concentration, the Cu-SiOx catalyst based MEA electrolyzer shows high ethylene Faradaic efficiencies of up to 65% at high ethylene current densities of up to 215 mA cm−2; and features sustained operation over 50 h.