bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of Parameter Screening to Derive Optimal Initial State Adjustments for Streamflow Forecasting
Authors: Mai Juliane , Arsenault Richard , Tolson Bryan A. , Latraverse Marco , Demeester Kenjy 
Published: August 2020

AbstractStreamflow forecasting is essential in many applications, including the management of hydropower reservoirs and of flood risks. To increase the performance of these hydrologic forecasts, a hydrological model is typically updated with optimal initial model states. These states are usually selected a priori and adjusted to obtain the optimal initial setup. The model states to adjust are generally selected by experts with deep knowledge of the model's behavior. These relationships are rarely documented and formalized, leading to difficulties in reproducibility and transferability to other models. The method here provides a fully automatized system to find the model states based on the parameter‐free sensitivity method of efficient elementary effects (EEE), which identifies the most informative variables of the hydrologic model CEQUEAU. The analysis is applied to 1,826 model setups for four Canadian basins. The identified states are formalized using clustering techniques to obtain adjustment “recipes” conditioned on given meteorological conditions. Several recipes are tested and compared to expert‐based recipes. The recipes are tested according to their ability to (a) obtain optimal initial states and (b) their forecast performance. The results show that (1) the EEE‐based recipes perform similarly or better than the expert‐based recipes in both objectives; (2) the recipes are similar across the four basins, highlighting their potential of spatial transferability; and (3) the adjustment of hydrologic model inputs significantly decreases forecast performance. The proposed approach to use EEE‐based recipes to obtain optimal initial states for forecasting is reproducible, objective, and suitable to be applied to other models and basins.
Excess Air Correction of SF6 and Other Dissolved Gases in Groundwater Impacted by Compressed Air From Drilling or Well Development
Authors: Poulsen David L. , Cook Peter G. , Dogramaci Shawan 
Published: August 2020

AbstractAtmospheric gases that dissolve in groundwater at the time of recharge are valuable tracers of groundwater residence time, but corrections are sometimes required. Low‐solubility gases like SF6 are particularly susceptible to the effects of excess air, which is generally assumed to occur at the time of recharge. If after excess air correction SF6 is still elevated above the expected concentration for water in equilibrium with the atmosphere, this is often attributed to a terrigenic source. We propose that compressed air used during and after well installation is a potential source of excess air, which can sometimes explain elevated SF6 concentrations from wells drilled in the last few decades. This concept is demonstrated by correcting elevated SF6 and CFC‐12 measurements from 55 wells at field sites in the Pilbara region of Western Australia with up to 10 mL(STP)/kg of atmospheric air from the time of drilling (2006–2016). The resulting SF6 and CFC‐12 concentrations are consistent with recharge between 1950 and 1970 for most wells. Excess air in recharge from that period could not have contained enough SF6 to explain the measured concentrations. This decoupling of excess air from recharge is potentially also significant for other gaseous age tracers with limited solubility including SF5CF3, Halon 1301, 39Ar, 85Kr, and 81Kr.
l-DOPA and consolidation of fear extinction learning among women with posttraumatic stress disorder
Authors: Cisler Josh M. , Privratsky Anthony A. , Sartin-Tarm Anneliis , Sellnow Kyrie , Ross Marisa , Weaver Shelby , Hahn Emily , Herringa Ryan J. , James George Andrew , Kilts Clinton D. 
Published: August 2020

AbstractThis study tested whether l-DOPA delivered during the consolidation window following fear extinction learning reduces subsequent fear responding among women with PTSD. Adult women diagnosed with PTSD completed a contextual fear acquisition and extinction task during fMRI and then immediately received either placebo (n = 34), 100/25 mg l-DOPA/carbidopa (n = 28), or 200/50 mg l-DOPA/carbidopa (n = 29). Participants completed a resting-state scan before the task and again 45 min following drug ingestion to characterize effects of l-DOPA on extinction memory neural reactivation patterns during consolidation. Twenty-four hours later, participants returned for tests of context renewal, extinction recall, and reinstatement during fMRI with concurrent skin conductance responding (SCR) assessment. Both active drug groups demonstrated increased reactivation of extinction encoding in the amygdala during the post-task resting-state scan. For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the 100 mg group compared to placebo. For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo. There was no evidence in SCR or neural activity that l-DOPA improved extinction recall. Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network. These results support a role for dopamine during the consolidation window in boosting reactivation of amygdala extinction encodings and reducing reinstatement, but not improving extinction recall, in women with PTSD.
Triggering a switch from basal- to luminal-like breast cancer subtype by the small-molecule diptoindonesin G via induction of GABARAPL1
Authors: Fan Minmin , Chen Jingwei , Gao Jian , Xue Wenwen , Wang Yixuan , Li Wuhao , Zhou Lin , Li Xin , Jiang Chengfei , Sun Yang , Wu Xuefeng , Wu Xudong , Ge Huiming , Shen Yan , Xu Qiang 
Published: August 2020

AbstractBreast cancer is a heterogeneous disease that includes different molecular subtypes. The basal-like subtype has a poor prognosis and a high recurrence rate, whereas the luminal-like subtype confers a more favorable patient prognosis partially due to anti-hormone therapy responsiveness. Here, we demonstrate that diptoindonesin G (Dip G), a natural product, exhibits robust differentiation-inducing activity in basal-like breast cancer cell lines and animal models. Specifically, Dip G treatment caused a partial transcriptome shift from basal to luminal gene expression signatures and prompted sensitization of basal-like breast tumors to tamoxifen therapy. Dip G upregulated the expression of both GABARAPL1 (GABAA receptor-associated protein-like 1) and ERβ. We revealed a previously unappreciated role of GABARAPL1 as a regulator in the specification of breast cancer subtypes that is dependent on ERβ levels. Our findings shed light on new therapeutic opportunities for basal-like breast cancer via a phenotype switch and indicate that Dip G may serve as a leading compound for the therapy of basal-like breast cancer.
Sequential combinations of chemotherapeutic agents with BH3 mimetics to treat rhabdomyosarcoma and avoid resistance
Authors: Alcon Clara , Manzano-Muñoz Albert , Prada Estela , Mora Jaume , Soriano Aroa , Guillén Gabriela , Gallego Soledad , Roma Josep , Samitier Josep , Villanueva Alberto , Montero Joan 
Published: August 2020

AbstractRhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood and adolescence. Refractory/relapsed RMS patients present a bad prognosis that combined with the lack of specific biomarkers impairs the development of new therapies. Here, we utilize dynamic BH3 profiling (DBP), a functional predictive biomarker that measures net changes in mitochondrial apoptotic signaling, to identify anti-apoptotic adaptations upon treatment. We employ this information to guide the use of BH3 mimetics to specifically inhibit BCL-2 pro-survival proteins, defeat resistance and avoid relapse. Indeed, we found that BH3 mimetics that selectively target anti-apoptotic BCL-xL and MCL-1, synergistically enhance the effect of clinically used chemotherapeutic agents vincristine and doxorubicin in RMS cells. We validated this strategy in vivo using a RMS patient-derived xenograft model and observed a reduction in tumor growth with a tendency to stabilization with the sequential combination of vincristine and the MCL-1 inhibitor S63845. We identified the molecular mechanism by which RMS cells acquire resistance to vincristine: an enhanced binding of BID and BAK to MCL-1 after drug exposure, which is suppressed by subsequently adding S63845. Our findings validate the use of DBP as a functional assay to predict treatment effectiveness in RMS and provide a rationale for combining BH3 mimetics with chemotherapeutic agents to avoid tumor resistance, improve treatment efficiency, and decrease undesired secondary effects.
Deubiquitination of CD36 by UCHL1 promotes foam cell formation
Authors: Xia Xiaohong , Xu Qiong , Liu Mingke , Chen Xuke , Liu Xiaolin , He Jinchan , Hu Tumei , Yu Cuifu , Huang Hongbiao , Liu Shiming , Liu Ningning 
Published: August 2020

AbstractAtherosclerosis-associated cardiovascular diseases are main causes leading to high mortality worldwide. Macrophage-derived foam cell formation via uptaking modified lipoproteins is the initial and core step in the process of atherosclerosis. Meanwhile, scavenger receptor is indispensable for the formation of foam cells. UCHL1, a deubiquitinase, has been widely studied in multiple cancers. UCHL1 could be an oncogene or a tumor suppressor in dependent of tumor types. It remains unknown whether UCHL1 influences cellular oxLDL uptake. Herein we show that UCHL1 deletion significantly inhibits lipid accumulation and foam cell formation. Subsequently, we found that UCHL1 inhibitor or siRNA downregulates the expression of CD36 protein whereas SR-A, ABCA1, ABCG1, Lox-1, and SR-B1 have no significant change. Furthermore, the treatment of UCHL1 inhibition increases the abundance of K48-polyubiquitin on CD36 and the suppression of lipid uptake induced by UCHL1 deficiency is attenuated by blocking CD36 activation. Our study concluded that UCHL1 deletion decreases foam cell formation by promoting the degradation of CD36 protein, indicating UCHL1 may be a potential target for atherosclerosis treatment.
LncRNA TTN-AS1 promotes the progression of cholangiocarcinoma via the miR-320a/neuropilin-1 axis
Authors: Zhu Huaqiang , Zhai Bo , He Changjun , Li Ziyi , Gao Hengjun , Niu Zheyu , Jiang Xian , Lu Jun , Sun Xueying 
Published: August 2020

AbstractNeuropilin-1 regulated by miR-320a participates in the progression of cholangiocarcinoma by serving as a co-receptor that activates multiple signaling pathways. The present study sought to investigate upstream lncRNAs that control the expression of miR-320a/neuropilin-1 axis and dissect some of the underlying mechanisms. Here we report lncRNA TTN-AS1 (titin-antisense RNA1) acts as a sponging ceRNA to downregulate miR-320a and is highly expressed in human cholangiocarcinoma tissues and cells. The expression of the above three molecules is correlated with the clinicopathologic parameters of cholangiocarcinoma patients. In this study, multiple bioinformatics tools and databases were employed to seek potential lncRNAs that have binding sites with miR-320a and TTN-AS1 was identified because it exhibited the largest folds of alteration between cholangiocarcinoma and normal bile duct epithelial cells. The regulatory role of TTN-AS1 on miR-320a was further evaluated by luciferase reporter and RNA pulldown assays, coupled with in situ hybridization and RNA immunoprecipitation analyses, which showed that TTN-AS1 bound to miR-320a through an argonaute2-dependent RNA interference pathway in the cytoplasm of cholangiocarcinoma cells. Knockdown and overexpression assays showed that the regulatory effect between TTN-AS1 and miR-320 was in a one-way manner. TTN-AS1 promoted the proliferation and migration of cholangiocarcinoma cells via the miR-320a/ neuropilin-1 axis. The function of TTN-AS1 on tumor growth and its interaction with miR-320a were confirmed in animal models. Further mechanistic studies revealed that TTA-AS1, through downregulating miR-320a, promoted cell cycle progression, epithelial–mesenchymal transition, and tumor angiogenesis by upregulating neuropilin-1, which co-interacted with the hepatocyte growth factor/c-Met and transforming growth factor (TGF)-β/TGF-β receptor I pathways. In conclusion, the present results demonstrate that lncRNA TTA-AS1 is a sponging ceRNA for miR-320a, which in turn downregulates neuropilin-1 in cholangiocarcinoma cells, indicating these three molecules represent potential biomarkers and therapeutic targets in the management of cholangiocarcinoma.
Water worlds in N-body simulations with fragmentation in systems without gaseous giants
Authors: Dugaro A. , de Elía G. C. , Darriba L. A. 
Published: August 2020

Aims. We analyze the formation and evolution of terrestrial-like planets around solar-type stars in the absence of gaseous giants. In particular, we focus on the physical and dynamical properties of those that survive in the system’s habitable zone (HZ). This investigation is based on a comparative study between N-body simulations that include fragmentation and others that consider all collisions as perfect mergers.
Methods. We use an N-body code, presented in a previous paper, that allows planetary fragmentation. We carry out three sets of 24 simulations for 400 Myr. Two sets are developed adopting a model that includes hit-and-run collisions and planetary fragmentation, each one with different values of the individual minimum mass allowed for the fragments. For the third set, we considered that all collisions lead to perfect mergers.
Results. The planetary systems produced in N-body simulations with and without fragmentation are broadly similar, though with some differences. In simulations with fragmentation, the formed planets have lower masses since part of them is distributed among collisional fragments. Additionally, those planets presented lower eccentricities, presumably due to dynamical friction with the generated fragments. Lastly, perfect mergers and hit-and-run collisions are the most common outcome. Regardless of the collisional treatment adopted, most of the planets that survive in the HZ start the simulation beyond the snow line, having very high final water contents. Such planets are called water worlds. The fragments’ contribution to their final mass and water content is negligible. Finally, the individual minimum mass for fragments may play an important role in the planets’ collisional history.
Conclusions. Collisional models that incorporate fragmentation and hit-and-run collisions lead to a more detailed description of the physical properties of the terrestrial-like planets formed. We conclude that planetary fragmentation is not a barrier to the formation of water worlds in the HZ. The results shown in this work suggest that further refinement is necessary to have a more realistic model of planetary formation.
Ex vivo Improvement of a von Willebrand Disease Type 2A Phenotype Using an Allele-Specific Small-Interfering RNA
Authors: de Jong Annika , Dirven Richard J. , Boender Johan , Atiq Ferdows , Anvar Seyed Yahya , Leebeek Frank W. G. , van Vlijmen Bart J. M. , Eikenboom Jeroen 
Published: August 2020

AbstractVon Willebrand disease (VWD) is the most common inherited bleeding disorder and is mainly caused by dominant-negative mutations in the multimeric protein von Willebrand factor (VWF). These mutations may either result in quantitative or qualitative defects in VWF. VWF is an endothelial protein that is secreted to the circulation upon endothelial activation. Once secreted, VWF multimers bind platelets and chaperone coagulation factor VIII in the circulation. Treatment of VWD focuses on increasing VWF plasma levels, but production and secretion of mutant VWF remain uninterrupted. Presence of circulating mutant VWF might, however, still affect normal hemostasis or functionalities of VWF beyond hemostasis. We hypothesized that inhibition of the production of mutant VWF improves the function of VWF overall and ameliorates VWD phenotypes. We previously proposed the use of allele-specific small-interfering RNAs (siRNAs) that target frequent VWF single nucleotide polymorphisms to inhibit mutant VWF. The aim of this study is to prove the functionality of these allele-specific siRNAs in endothelial colony-forming cells (ECFCs). We isolated ECFCs from a VWD type 2A patient with an intracellular multimerization defect, reduced VWF collagen binding, and a defective processing of proVWF to VWF. After transfection of an allele-specific siRNA that specifically inhibited expression of mutant VWF, we showed amelioration of the laboratory phenotype, with normalization of the VWF collagen binding, improvement in VWF multimers, and enhanced VWF processing. Altogether, we prove that allele-specific inhibition of the production of mutant VWF by siRNAs is a promising therapeutic strategy to improve VWD phenotypes.
A robust and interpretable end-to-end deep learning model for cytometry data
Authors: Hu Zicheng , Tang Alice , Singh Jaiveer , Bhattacharya Sanchita , Butte Atul J. 
Published: August 2020

Significance
Cytometry technologies are able to profile immune cells at single-cell resolution. They are widely used for both clinical diagnosis and biological research. We developed a deep learning model for analyzing cytometry data. We demonstrated that the deep learning model accurately diagnoses the latent cytomegalovirus (CMV) in healthy individuals. In addition, we developed a method for interpreting the deep learning model, allowing us to identify biomarkers associated with latent CMV infection. The deep learning model is widely applicable to other cytometry data related to human diseases.
Transit Oriented Development (TOD) Policies and Station Area Development in Asian Cities
Authors: Kidokoro Tetsuo 
Published: August 2020

Abstract
Many metropolitan cities of Asia are planning and implementing extensive investment in mass transit network and thus, are now at the threshold of whether they become transit cities or car traffic saturation cities. Promotion of Transit Oriented development (TOD) policies will be a key to move forward to transit cities. TOD should consider: transit oriented regional growth management plan, station area zoning regulations (mixed-use, minimum density, maximum parking, etc.), joint development among local governments, transit agencies, private developers, institutional mechanism for the public and private cooperation in station area development. In this paper, the cases from the cities in Japan, United States and the Southeast Asia are examined including Toyama in Japan, Kuala Lumpur in Malaysia and Jakarta in Indonesia. In conclusion, the following are discussed as the factors for successful Implementation of TOD in Asian Cities. Shift from highway-based zoning to transit oriented zoning: Creation of institutional mechanism for the public and private cooperation in the station area development, balance between public benefit and private benefit, connection of transit service and affordable housing, and, multi-modal connection planning including walking.
Dealing with Private and Public Space Interface Problem in TOD Area. Case study of Batuceper Station, Tangerang
Authors: Abadi Agustinus Adib , Nugraha Marestu Rizki 
Published: August 2020

Abstract
The Indonesian government has implemented the new strategy of Transit-Oriented Development (TOD) in dealing with urban issues, especially to overcome some of the urbanization effects such as housing deficiency, traffic jams, and private car usage. Under the PPP scheme, national private companies have initiated developing apartments in TOD of Batuceper station, located at the most populated district in the city of Tangerang. The mixture of residences with other public activities at TOD creates problems of privacy as the concern of accessibility and connectivity in the development principles. An in-depth study to examine this problem is required. Thus, this paper reviews various research related to the private and public spatial interface in the mix facilities area. This paper analyses the possible private and private space interface strategy between an apartment and other functions or activities at TOD Batuceper station development. The findings of this paper suggested that apartment design at the TOD area is a complex problem, and the proper strategy to solve such spatial interface problems depends on its linking hierarchy with other activities in the development area.
Re-orienting TOD concept and implementation in Jakarta
Authors: Suryani Sri , Harun Ismet B. , Astuti Wahyu K. 
Published: August 2020

Abstract
Since the 1990s, Jakarta city planning has introduced Transit-Oriented Development (TOD) as solution to dominant auto-mobility and sprawl to regional cities in Bogor, Depok, Tangerang, and Bekasi (JABODETABEK) by improving accessibility and inter-connectivity in urban mobility. Nevertheless, less has been investigated to what extent the on-going implementation in TOD projects departs from the means of TOD as planning approach in response to the urban problems. This paper aims to investigate TOD concept and implementation in Jakarta by proposing a comparative study on TOD in Japan and JABODETABEK, by using desk study in the planning documents and TOD projects. In each case, the investigation focuses on three sections; planning, implementation, and output. This paper reveals that the current TOD projects in Jakarta are based on single land development within proximity of TOD stations that maximizes private development benefits. Therefore, it concludes that the “TOD” projects in Jakarta have not yet met the TOD principles as a planning approach in response to the urban sprawls and integrated development.
Transit Passengers-Oriented Built Environment: An Evaluation of Mode Shift and Street Network and Design
Authors: Prayogi Luthfi , Aqli Wafirul 
Published: August 2020

Abstract
Recently there have been efforts on designing a built environment that encourages its residents to take transit more and use personal motorised vehicles less, commonly known as transit-oriented development (TOD). The outcome of such efforts can be evaluated by the mode shift from using a private motorised vehicle to taking transit occurring among the residents of the built environment. This article explores the mode shift that occurred among Transjakarta BRT corridor 1 passenger that is triggered by the street network and design around the Transjakarta corridor 1 bus stops. This article also evaluates the qualities of the street network and design around the mentioned bus stops to complement the passengers’ mode shift explanation. This article is written using a qualitative approach and inductive rationalization. Information regarding the passengers’ mode shift is obtained through an indirect interview, while evaluation on the qualities of the street network and design is carried out using space syntax analysis. This article finds that the magnitude of mode shift to taking Transjakarta corridor 1 due to the qualities of the street network and design around the bus stops is not significant. In line with that, the integration and connectivity of the streets around the observed segment of Transjakarta corridor 1 is relatively low. This article concludes that even though mode shift to taking Transjakarta corridor 1 is occurring, the street network and design around the Transjakarta bus stops have not contributed significantly in triggering the mode shift. This article proposes a relatively new approach in evaluating TOD, which is by simultaneously assessing the citizens’ habit and preference and the built environment.