bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Investment Rulemaking in Asia: Between Regionalism and Domestication
Authors: Hsieh Pasha L. 
Published: January 2023

AbstractThe article analyses investment rulemaking in new Asian regionalism in the context of evolving national legislation and regional trade strategies. It argues that the Association of Southeast Asian Nations (ASEAN) and the Regional Comprehensive Economic Partnership (RCEP) represent Asia's pragmatic incrementalism in reforming the investment regime. The process reinforces the relationship between international economic law and domestic investment laws. In tandem with transforming international investment agreements, ASEAN expedited investment and services trade, and established the modern investor–state dispute settlement (ISDS) mechanism. The RCEP further buttresses the ASEAN centrality in regional frameworks by consolidating ASEAN Plus One agreements. Yet, the RCEP's omission of ISDS reflects a distinct approach that may confront challenges to state-to-state proceedings and treaty shopping under overlapping pacts. Finally, the research sheds light on Asian countries' recent investment agreements and domestic dispute settlement that complement the liberal international order. These developments provide valuable models for developing countries and contribute to the understanding of global investment reforms from an Asian perspective.
The Past, Present, and Future of Domestic Investment Laws and International Economic Law
Authors: Hepburn Jarrod 
Published: January 2023

AbstractThis article considers the past, present, and future of domestic investment laws. Its focus is on the ‘facilitative’ investment law, which aims to encourage foreign investment by granting substantive protections to foreign investors and consent to international arbitration over disputes with foreign investors. The article first contends that states had independent reasons to enact such facilitative investment laws alongside investment treaties, even though investment treaties perform very similar functions. Secondly, the article argues that investment laws can be characterized either as unilaterally assumed international obligations of states or simply as domestic laws of states, with differing consequences under each characterization. Thirdly, the article proposes four possible futures for facilitative investment laws: contamination, continuation, compromise, and contestation.
Concurrent Precipitation Extremes Modulate the Response of Rice Transplanting Date to Preseason Temperature Extremes in China
Authors: Liu Yiqing , Liu Weihang , Li Yan , Ye Tao , Chen Shuo , Li Zitong , Sun Ran 
Published: January 2023

AbstractUnderstanding how crop phenology responds to climate change is critical for enabling agricultural adaptation measures. Pre‐season temperature alone leads to well‐understood changes in crop phenology. Nevertheless, the modulation effect of concurrent precipitation extremes on the response to temperature extremes has been largely under‐addressed. Here, we investigate the response of rice transplanting dates to pre‐season temperature extremes and reveal the modulation effects of concurrent precipitation extremes by using station‐observed rice transplanting dates from 1981 to 2018 across mainland China. We also evaluate the performance of a remotely sensed phenology product, ChinaCropPhen1km, in reproducing the above temperature responses and modulation effects. Our results showed that transplanting dates tended to advance in response to an extremely hot pre‐season, while concurrent extreme drought offset the advance by up to 2.6 days. Transplanting dates tended to be delayed in response to an extremely cold pre‐season, while concurrent extreme precipitation exacerbated the delay by up to 1 day. Responses to temperature extremes and modulation effects were divergent across different regions. Under extremely hot conditions, transplanting dates advanced further in hotter and wetter regions, while under extremely cold pre‐seasons, transplanting dates delayed less in colder and drier regions. Transplanting dates from the ChinaCropPhen1km product underestimated the responses to temperature extremes by up to 4.7 days and detected the opposite modulation effect compared to those obtained from observations. Our results highlight that the need to improve our understanding and modeling of modulation effects of precipitation extremes on temperature–phenology relationship, which benefits the field of agriculture risk analysis and climate change adaptation.
A Gradient Based Subgrid‐Scale Parameterization for Ocean Mesoscale Eddies
Authors: Khani Sina , Dawson Clinton N. 
Published: January 2023

AbstractMesoscale eddies play an important role in transport of heat and biogeochemical tracers in the global ocean circulation. Resolving these energetic eddies, however, is challenging in ocean general circulation models (OGCM) because it requires a horizontal grid spacing of ≲1/8° that is computationally expensive. As a result, we are required to parameterize mesoscale eddy effects on large‐scale ocean flows. In this work, we introduce a new subgrid‐scale (SGS) model that is developed based on a Taylor series expansion of resolved variables to parameterize subgrid mesoscale eddy transports and momentum fluxes in OGCM. We have performed an a priori study to evaluate the performance of our new gradient model using high‐resolution ocean simulations. Our results show that the gradient model well predicts the actual SGS thickness fluxes in the zonal and meridional directions in coarse‐resolution simulations with the grid spacing ≳1/4°. The unresolved kinetic energy at the ocean surface is also skillfully estimated. More importantly, unlike current mesoscale eddy parameterizations, which are mainly developed based on an assumption of flat bottom ocean, our new SGS model can capture the structure of unresolved standing meanders at the ocean surface. We have also developed a dynamic procedure for setting in non‐dimensional parameters in our new parameterization through a non‐ad hoc and tuning‐free method. Overall, this work suggests that implementing the gradient model in OGCM can improve the model accuracy with an affordable computational cost in eddy‐permitting and non‐eddying simulations.
Uncertainty Decomposition to Understand the Influence of Water Systems Model Error in Climate Vulnerability Assessments
Authors: Steinschneider Scott , Herman Jonathan D. , Kucharski John , Abellera Marriah , Ruggiero Peter 
Published: January 2023

AbstractClimate vulnerability assessments rely on water infrastructure system models that imperfectly predict performance metrics under ensembles of future scenarios. There is a benefit to reduced complexity system representations to support these assessments, especially when large ensembles are used to better characterize future uncertainties. An important question is whether the total uncertainty in the output metrics is primarily attributable to the climate ensemble or to the systems model itself. Here we develop a method to address this question by combining time series error models of performance metrics with time‐varying Sobol sensitivity analysis. The method is applied to a reduced complexity multi‐reservoir systems model of the Sacramento‐San Joaquin River Basin in California to demonstrate the decomposition of flood risk and water supply uncertainties under an ensemble of climate change scenarios. The results show that the contribution of systems model error to total uncertainty is small (∼5%–15%) relative to climate based uncertainties. This indicates that the reduced complexity systems model is sufficiently accurate for use in the context of the vulnerability assessment. We also observe that climate uncertainty is dominated by the choice of general circulation model and its interactive effects with the representative concentration pathway (RCP), rather than the RCP alone. This observation has implications for how climate vulnerabilities should be interpreted.
Inhibiting nighttime melatonin and boosting cortisol increase patrolling monocytes, phagocytosis, and myelination in a murine model of multiple sclerosis
Authors: Ghareghani Majid , Pons Vincent , Laflamme Nataly , Zibara Kazem , Rivest Serge 
Published: January 2023

AbstractConflicting results on melatonin synthesis in multiple sclerosis (MS) have been reported due to variabilities in patient lifestyles, which are not considered when supplementing melatonin. Since melatonin acts through its receptors, we identified melatonin receptors in oligodendrocytes (OLs) in the corpus callosum, where demyelination occurs; the subventricular zone, where neural stem/progenitor cells (NSPCs) are located; and the choroid plexus, which functions as a blood-cerebrospinal fluid barrier. Moreover, using chimeric mice, resident macrophages were found to express melatonin receptors, whereas bone marrow-derived macrophages lost this expression in the demyelinated brain. Next, we showed that cuprizone-fed mice, which is an MS model, tended to have increased melatonin levels. While we used different approaches to alter the circadian rhythm of melatonin and cortisol, only the constant light approach increased NSPC proliferation and differentiation to oligodendrocyte precursor cells (OPCs), OPCs maturation to OLs and recruitment to the site of demyelination, the number of patrolling monocytes, and phagocytosis. In contrast, constant darkness and exogenous melatonin exacerbated these events and amplified monocyte infiltration. Therefore, melatonin should not be considered a universal remedy, as is currently claimed. Our data emphasize the importance of monitoring melatonin/cortisol oscillations in each MS patient by considering diet and lifestyle to avoid melatonin overdose.
NCK-associated protein 1 regulates metastasis and is a novel prognostic marker for colorectal cancer
Authors: Kwon Mi Ri , Lee Jae Hee , Park Jin , Park Seok Soon , Ju Eun Jin , Ko Eun Jung , Shin Seol Hwa , Son Ga Won , Lee Hye Won , Kim Yeon Joo , Song Si Yeol , Jeong Seong-Yun , Choi Eun Kyung 
Published: January 2023

AbstractMetastatic colorectal cancer (CRC) remains a substantial problem for mortality and requires screening and early detection efforts to increase survival. Epithelial-mesenchymal transition (EMT) and circulation of tumor cells in the blood play important roles in metastasis. To identify a novel target for metastasis of CRC, we conducted a gene microarray analysis using extracted RNA from the blood of preclinical models. We found that NCK-associated protein 1 (NCKAP1) was significantly increased in the blood RNA of patient-derived xenograft (PDX) models of colon cancer. In the NCKAP1 gene knockdown-induced human colon cancer cell lines HCT116 and HT29, there was a reduced wound healing area and significant inhibition of migration and invasion. As the result of marker screening for cytoskeleton and cellular interactions, CRC treated with siRNA of NCKAP1 exhibited significant induction of CDH1 and phalloidin expression, which indicates enhanced adherent cell junctions and cytoskeleton. In HCT116 cells with a mesenchymal state induced by TGFβ1, metastasis was inhibited by NCKAP1 gene knockdown through the inhibition of migration, and there was increased CTNNB1 expression and decreased FN expression. We established metastasis models for colon cancer to liver transition by intrasplenic injection shRNA of NCKAP1-transfected HCT116 cells or by implanting tumor tissue generated with the cells on cecal pouch. In metastasis xenograft models, tumor growth and liver metastasis were markedly reduced. Taken together, these data demonstrate that NCKAP1 is a novel gene regulating EMT that can contribute to developing a diagnostic marker for the progression of metastasis and new therapeutics for metastatic CRC treatment.
Significance of HLA in the development of Graves’ orbitopathy
Authors: Stasiak Magdalena , Zawadzka-Starczewska Katarzyna , Tymoniuk Bogusław , Stasiak Bartłomiej , Lewiński Andrzej 
Published: January 2023

AbstractGraves’ disease (GD), similarly to most autoimmune disease, is triggered by environmental factors in genetically predisposed individuals. Particular HLA alleles increase or decrease GD risk. No such correlation was demonstrated for Graves’ orbitopathy (GO) in Caucasian population. HLA-A, -B, -C, -DQB1 and -DRB1 genotyping was performed using a high-resolution method in a total number of 2378 persons including 70 patients with GO, 91 patients with non-GO GD and 2217 healthy controls to compare allele frequencies between GO, non-GO and controls. Significant associations between GO and HLA profile were demonstrated, with HLA-A*01:01, -A*32:01, -B*37:01, -B*39:01, -B*42:01, -C*08:02, C*03:02, DRB1*03:01, DRB1*14:01 and DQB1*02:01 being genetic markers of increased risk of GO, and HLA-C*04:01, -C*03:04, -C*07:02 and -DRB1*15:02 being protective alleles. Moreover, correlations between HLA alleles and increased or decreased risk of non-GO GD, but with no impact on risk of GO development, were revealed. Identification of these groups of GO-related and GO-protective alleles, as well as the alleles strongly related to non-GO GD, constitutes an important step in a development of personalized medicine, with individual risk assessment and patient-tailored treatment.
Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia
Authors: Cheney Alexandra M. , Costello Stephanann M. , Pinkham Nicholas V. , Waldum Annie , Broadaway Susan C. , Cotrina-Vidal Maria , Mergy Marc , Tripet Brian , Kominsky Douglas J. , Grifka-Walk Heather M. , Kaufmann Horacio , Norcliffe-Kaufmann Lucy , Peach Jesse T. , Bothner Brian , Lefcort Frances , Copié Valérie , Walk Seth T. 
Published: January 2023

AbstractFamilial dysautonomia (FD) is a rare genetic neurologic disorder caused by impaired neuronal development and progressive degeneration of both the peripheral and central nervous systems. FD is monogenic, with >99.4% of patients sharing an identical point mutation in the elongator acetyltransferase complex subunit 1 (ELP1) gene, providing a relatively simple genetic background in which to identify modifiable factors that influence pathology. Gastrointestinal symptoms and metabolic deficits are common among FD patients, which supports the hypothesis that the gut microbiome and metabolome are altered and dysfunctional compared to healthy individuals. Here we show significant differences in gut microbiome composition (16 S rRNA gene sequencing of stool samples) and NMR-based stool and serum metabolomes between a cohort of FD patients (~14% of patients worldwide) and their cohabitating, healthy relatives. We show that key observations in human subjects are recapitulated in a neuron-specific Elp1-deficient mouse model, and that cohousing mutant and littermate control mice ameliorates gut microbiome dysbiosis, improves deficits in gut transit, and reduces disease severity. Our results provide evidence that neurologic deficits in FD alter the structure and function of the gut microbiome, which shifts overall host metabolism to perpetuate further neurodegeneration.
Volumetric additive manufacturing of pristine silk-based (bio)inks
Authors: Xie Maobin , Lian Liming , Mu Xuan , Luo Zeyu , Garciamendez-Mijares Carlos Ezio , Zhang Zhenrui , López Arturo , Manríquez Jennifer , Kuang Xiao , Wu Junqi , Sahoo Jugal Kishore , González Federico Zertuche , Li Gang , Tang Guosheng , Maharjan Sushila , Guo Jie , Kaplan David L. , Zhang Yu Shrike 
Published: January 2023

AbstractVolumetric additive manufacturing (VAM) enables fast photopolymerization of three-dimensional constructs by illuminating dynamically evolving light patterns in the entire build volume. However, the lack of bioinks suitable for VAM is a critical limitation. This study reports rapid volumetric (bio)printing of pristine, unmodified silk-based (silk sericin (SS) and silk fibroin (SF)) (bio)inks to form sophisticated shapes and architectures. Of interest, combined with post-fabrication processing, the (bio)printed SS constructs reveal properties including reversible as well as repeated shrinkage and expansion, or shape-memory; whereas the (bio)printed SF constructs exhibit tunable mechanical performances ranging from a few hundred Pa to hundreds of MPa. Both types of silk-based (bio)inks are cytocompatible. This work supplies expanded bioink libraries for VAM and provides a path forward for rapid volumetric manufacturing of silk constructs, towards broadened biomedical applications.
Stress promotes RNA G-quadruplex folding in human cells
Authors: Kharel Prakash , Fay Marta , Manasova Ekaterina V. , Anderson Paul J. , Kurkin Alexander V. , Guo Junjie U. , Ivanov Pavel 
Published: January 2023

AbstractGuanine (G)-rich nucleic acids can fold into G-quadruplex (G4) structures under permissive conditions. Although many RNAs contain sequences that fold into RNA G4s (rG4s) in vitro, their folding and functions in vivo are not well understood. In this report, we showed that the folding of putative rG4s in human cells into rG4 structures is dynamically regulated under stress. By using high-throughput dimethylsulfate (DMS) probing, we identified hundreds of endogenous stress-induced rG4s, and validated them by using an rG4 pull-down approach. Our results demonstrate that stress-induced rG4s are enriched in mRNA 3′-untranslated regions and enhance mRNA stability. Furthermore, stress-induced rG4 folding is readily reversible upon stress removal. In summary, our study revealed the dynamic regulation of rG4 folding in human cells and suggested that widespread rG4 motifs may have a global regulatory impact on mRNA stability and cellular stress response.
Discovery and biosynthesis of karnamicins as angiotensin converting enzyme inhibitors
Authors: Yu Zhiyin , Huang Jian-Ping , Yang Jing , Liu Chongxi , Yan Yijun , Wang Li , Zhao Junwei , Chen Yin , Xiang Wensheng , Huang Sheng-Xiong 
Published: January 2023

AbstractAngiotensin-converting enzyme inhibitors are widely used for treatment of hypertension and related diseases. Here, six karnamicins E1-E6 (1–6), which bear fully substituted hydroxypyridine and thiazole moieties are characterized from the rare actinobacterium Lechevalieria rhizosphaerae NEAU-A2. Through a combination of isotopic labeling, genome mining, and enzymatic characterization studies, the programmed assembly of the fully substituted hydroxypyridine moiety in karnamicin is proposed to be due to sequential operation of a hybrid polyketide synthase-nonribosomal peptide synthetase, two regioselective pyridine ring flavoprotein hydroxylases, and a methyltransferase. Based on AlphaFold protein structures predictions, molecular docking, and site-directed mutagenesis, we find that two pyridine hydroxylases deploy active site residues distinct from other flavoprotein monooxygenases to direct the chemo- and regioselective hydroxylation of the pyridine nucleus. Pleasingly, karnamicins show significant angiotensin-converting enzyme inhibitory activity with IC50 values ranging from 0.24 to 5.81 μM, suggesting their potential use for the treatment of hypertension and related diseases.
Near-infrared-IIb emitting single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown after traumatic brain injury
Authors: Huang Biao , Tang Tao , Chen Shi-Hui , Li Hao , Sun Zhi-Jun , Zhang Zhi-Lin , Zhang Mingxi , Cui Ran 
Published: January 2023

AbstractThe blood-brain barrier breakdown, as a prominent feature after traumatic brain injury, always triggers a cascade of biochemical events like inflammatory response and free radical-mediated oxidative damage, leading to neurological dysfunction. The dynamic monitoring the status of blood-brain barrier will provide potent guidance for adopting appropriate clinical intervention. Here, we engineer a near-infrared-IIb Ag2Te quantum dot-based Mn single-atom catalyst for imaging-guided therapy of blood-brain barrier breakdown of mice after traumatic brain injury. The dynamic change of blood-brain barrier, including the transient cerebral hypoperfusion and cerebrovascular damage, could be resolved with high spatiotemporal resolution (150 ms and ~ 9.6 µm). Notably, the isolated single Mn atoms on the surface of Ag2Te exhibited excellent catalytic activity for scavenging reactive oxygen species to alleviate neuroinflammation in brains. The timely injection of Mn single-atom catalyst guided by imaging significantly promoted the reconstruction of blood-brain barrier and recovery of neurological function after traumatic brain injury.
Force-induced ion generation in zwitterionic hydrogels for a sensitive silent-speech sensor
Authors: Xu Sijia , Yu Jie-Xiang , Guo Hongshuang , Tian Shu , Long You , Yang Jing , Zhang Lei 
Published: January 2023

AbstractHuman-sensitive mechanosensation depends on ionic currents controlled by skin mechanoreceptors. Inspired by the sensory behavior of skin, we investigate zwitterionic hydrogels that generate ions under an applied force in a mobile-ion-free system. Within this system, water dissociates as the distance between zwitterions reduces under an applied pressure. Meanwhile, zwitterionic segments can provide migration channels for the generated ions, significantly facilitating ion transport. These combined effects endow a mobile-ion-free zwitterionic skin sensor with sensitive transduction of pressure into ionic currents, achieving a sensitivity up to five times that of nonionic hydrogels. The signal response time, which relies on the crosslinking degree of the zwitterionic hydrogel, was ~38 ms, comparable to that of natural skin. The skin sensor was incorporated into a universal throat-worn silent-speech recognition system that transforms the tiny signals of laryngeal mechanical vibrations into silent speech.
Coupled induction of prophage and virulence factors during tick transmission of the Lyme disease spirochete
Authors: Wachter Jenny , Cheff Britney , Hillman Chad , Carracoi Valentina , Dorward David W. , Martens Craig , Barbian Kent , Nardone Glenn , Renee Olano L. , Kinnersley Margie , Secor Patrick R. , Rosa Patricia A. 
Published: January 2023

AbstractThe alternative sigma factor RpoS plays a central role in the critical host-adaptive response of the Lyme disease spirochete, Borrelia burgdorferi. We previously identified bbd18 as a negative regulator of RpoS but could not inactivate bbd18 in wild-type spirochetes. In the current study we employed an inducible bbd18 gene to demonstrate the essential nature of BBD18 for viability of wild-type spirochetes in vitro and at a unique point in vivo. Transcriptomic analyses of BBD18-depleted cells demonstrated global induction of RpoS-dependent genes prior to lysis, with the absolute requirement for BBD18, both in vitro and in vivo, circumvented by deletion of rpoS. The increased expression of plasmid prophage genes and the presence of phage particles in the supernatants of lysing cultures indicate that RpoS regulates phage lysis-lysogeny decisions. Through this work we identify a mechanistic link between endogenous prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete.