bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARRT Development for the Upcoming Human Exploration Missions
Authors: Hu S. , Monadjemi S. , Barzilla J. E. , Semones E. 
Published: September 2020

AbstractThe health risks of space radiation present big challenges to space exploration, with the possibility of large Energetic Solar Particle Events (ESPEs) inducing Acute Radiation Sickness (ARS) during upcoming Artemis missions. An operational software Acute Radiation Risks Tool (ARRT) was developed to directly use measurements from onboard dosimeters to project organ doses during times of increased radiation exposure, so that any possible ARS risks of the astronauts can be modeled and monitored in real time using a data stream at the astronaut location. To enable ARRT to handle variant scenarios of any possible ESPEs in an automatic manner for mission operation, two data sets were employed in developing its modules, one involving historical solar protons recorded over the past four decades and the other using the real‐time telemetry readings of dosimeters onboard International Space Station (ISS). Though vastly different in terms of data cadence, smoothness, and data gaps, all events in these data sets can be correctly processed to output organ doses and ARS risks and generate flight notes for communication within the Flight Control Team (FCT). All these tasks are completed with close interactions between multiple modules developed with many state‐of‐the‐art facilities of full stack web applications. This work demonstrates that ARRT meets the requirement to project radiation exposure and to provide clinical guidelines in very short time steps as the ESPE unfolds, even for the longest event in data sets, making this tool eligible to be tested during the upcoming unmanned Artemis mission and utilized in future space exploration.
Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study
Authors: Yu Hui , Lin Liangbin , Zhang Zhiqiang , Zhang Huiyuan , Hu Hongbo 
Published: September 2020

AbstractNF-κB pathway consists of canonical and non-canonical pathways. The canonical NF-κB is activated by various stimuli, transducing a quick but transient transcriptional activity, to regulate the expression of various proinflammatory genes and also serve as the critical mediator for inflammatory response. Meanwhile, the activation of the non-canonical NF-κB pathway occurs through a handful of TNF receptor superfamily members. Since the activation of this pathway involves protein synthesis, the kinetics of non-canonical NF-κB activation is slow but persistent, in concordance with its biological functions in the development of immune cell and lymphoid organ, immune homeostasis and immune response. The activation of the canonical and non-canonical NF-κB pathway is tightly controlled, highlighting the vital roles of ubiquitination in these pathways. Emerging studies indicate that dysregulated NF-κB activity causes inflammation-related diseases as well as cancers, and NF-κB has been long proposed as the potential target for therapy of diseases. This review attempts to summarize our current knowledge and updates on the mechanisms of NF-κB pathway regulation and the potential therapeutic application of inhibition of NF-κB signaling in cancer and inflammatory diseases.
Developing a data-driven algorithm for guiding selection between cognitive behavioral therapy, fluoxetine, and combination treatment for adolescent depression
Authors: Gunlicks-Stoessel Meredith , Klimes-Dougan Bonnie , VanZomeren Adrienne , Ma Sisi 
Published: September 2020

AbstractTreating adolescent depression effectively requires providing interventions that are optimally suited to patients’ individual characteristics and needs. Therefore, we aim to develop an algorithm that matches patients with optimal treatment among cognitive-behavioral therapy (CBT), fluoxetine (FLX), and combination treatment (COMB). We leveraged data from a completed clinical trial, the Treatment for adolescents with depression study, where a wide range of demographic, clinical, and psychosocial measures were collected from adolescents diagnosed with major depressive disorder prior to treatment. Machine-learning techniques were employed to derive a model that predicts treatment response (week 12 children’s depression rating scale-revised [CDRS-R]) to CBT, FLX, and COMB. The resulting model successfully identified subgroups of patients that respond preferentially to specific types of treatment. Specifically, our model identified a subgroup of patients (25%) that achieved on average a 16.9 point benefit on the CDRS-R from FLX compared to CBT. The model also identified a subgroup of patients (50%) that achieved an average benefit up to 19.0 points from COMB compared to CBT. Physical illness and disability were identified as overall predictors of response to treatment, regardless of treatment type, whereas baseline CDRS-R, psychosomatic symptoms, school missed, view of self, treatment expectations, and attention problems determined the patients’ response to specific treatments. The model developed in this study provides a critical starting point for personalized treatment planning for adolescent depression.
Arsenic trioxide enhances the chemotherapeutic efficiency of cisplatin in cholangiocarcinoma cells via inhibiting the 14-3-3ε-mediated survival mechanism
Authors: Jin Ming , Wu Liunan , Chen Shuai , Cai Rong , Dai Yi , Yang Haojun , Tang Liming , Li Yuan 
Published: September 2020

AbstractCholangiocarcinoma (CCA) is the second most frequent primary liver carcinoma with high degrees of malignancy and mortality. Chemotherapy plays a key role in the treatment of CCA, however, the low chemotherapeutic efficiency leads to a bottleneck. So unraveling the potential mechanisms to enhance the efficiency (reduced the dosage and enhanced the effects of chemotherapy drugs) and identifying alternative therapeutic strategies in CCA are urgently needed. Here, we found that, in CCA cells, when cisplatin (CDDP) displayed anti-tumor effects, it activated 14-3-3ε simultaneously, which in turn formed a survival mechanism via the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI-3K/Akt). However, low concentrations of arsenic trioxide (ATO) could disrupt such survival mechanism and enhanced the efficiency. For the molecular mechanisms, ATO attenuated 14-3-3ε at both transcriptional and post-transcriptional (ubiquitination degradation) levels. Such repressive effect blocked the activation of PI-3K/Akt, and its downstream anti-apoptotic factors, B-cell lymphoma 2 (Bcl-2), and survivin. Collectively, our present study revealed that the synergistic effects of ATO and CDDP could be a novel approach for enhancing the efficiency, which provides an innovative therapeutic vision for the treatment of CCA.
Dissipation of electron-beam-driven plasma wakes
Authors: Zgadzaj Rafal , Silva T. , Khudyakov V. K. , Sosedkin A. , Allen J. , Gessner S. , Li Zhengyan , Litos M. , Vieira J. , Lotov K. V. , Hogan M. J. , Yakimenko V. , Downer M. C. 
Published: September 2020

AbstractMetre-scale plasma wakefield accelerators have imparted energy gain approaching 10 gigaelectronvolts to single nano-Coulomb electron bunches. To reach useful average currents, however, the enormous energy density that the driver deposits into the wake must be removed efficiently between shots. Yet mechanisms by which wakes dissipate their energy into surrounding plasma remain poorly understood. Here, we report picosecond-time-resolved, grazing-angle optical shadowgraphic measurements and large-scale particle-in-cell simulations of ion channels emerging from broken wakes that electron bunches from the SLAC linac generate in tenuous lithium plasma. Measurements show the channel boundary expands radially at 1 million metres-per-second for over a nanosecond. Simulations show that ions and electrons that the original wake propels outward, carrying 90 percent of its energy, drive this expansion by impact-ionizing surrounding neutral lithium. The results provide a basis for understanding global thermodynamics of multi-GeV plasma accelerators, which underlie their viability for applications demanding high average beam current.
Fundamental dissipation due to bound fermions in the zero-temperature limit
Authors: Autti S. , Ahlstrom S. L. , Haley R. P. , Jennings A. , Pickett G. R. , Poole M. , Schanen R. , Soldatov A. A. , Tsepelin V. , Vonka J. , Wilcox T. , Woods A. J. , Zmeev D. E. 
Published: September 2020

AbstractThe ground state of a fermionic condensate is well protected against perturbations in the presence of an isotropic gap. Regions of gap suppression, surfaces and vortex cores which host Andreev-bound states, seemingly lift that strict protection. Here we show that in superfluid 3He the role of bound states is more subtle: when a macroscopic object moves in the superfluid at velocities exceeding the Landau critical velocity, little to no bulk pair breaking takes place, while the damping observed originates from the bound states covering the moving object. We identify two separate timescales that govern the bound state dynamics, one of them much longer than theoretically anticipated, and show that the bound states do not interact with bulk excitations.
CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis
Authors: Hao Jian-Wei , Wang Juan , Guo Huiling , Zhao Yin-Yue , Sun Hui-Hui , Li Yi-Fan , Lai Xiao-Ying , Zhao Ning , Wang Xu , Xie Changchuan , Hong Lixin , Huang Xi , Wang Hong-Rui , Li Cheng-Bin , Liang Bin , Chen Shuai , Zhao Tong-Jin 
Published: September 2020

AbstractFatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.
Straightforward preparation of supramolecular Janus nanorods by hydrogen bonding of end-functionalized polymers
Authors: Han Shuaiyuan , Pensec Sandrine , Yilmaz Dijwar , Lorthioir Cédric , Jestin Jacques , Guigner Jean-Michel , Niepceron Frédérick , Rieger Jutta , Stoffelbach François , Nicol Erwan , Colombani Olivier , Bouteiller Laurent 
Published: September 2020

AbstractJanus cylinders are one-dimensional colloids that have two faces with different compositions and functionalities, and are useful as building blocks for advanced functional materials. Such anisotropic objects are difficult to prepare with nanometric dimensions. Here we describe a robust and versatile strategy to form micrometer long Janus nanorods with diameters in the 10-nanometer range, by self-assembly in water of end-functionalized polymers. The Janus topology is not a result of the phase segregation of incompatible polymer arms, but is driven by the interactions between unsymmetrical and complementary hydrogen bonded stickers. Therefore, even compatible polymers can be used to form these Janus objects. In fact, any polymers should qualify, as long as they do not prevent co-assembly of the stickers. To illustrate their applicative potential, we show that these Janus nanorods can efficiently stabilize oil-in-water emulsions.
Estimating retention benchmarks for salvage logging to protect biodiversity
Authors: Thorn Simon , Chao Anne , Georgiev Kostadin B. , Müller Jörg , Bässler Claus , Campbell John L. , Castro Jorge , Chen Yan-Han , Choi Chang-Yong , Cobb Tyler P. , Donato Daniel C. , Durska Ewa , Macdonald Ellen , Feldhaar Heike , Fontaine Joseph B. , Fornwalt Paula J. , Hernández Raquel María Hernández , Hutto Richard L. , Koivula Matti , Lee Eun-Jae , Lindenmayer David , Mikusiński Grzegorz , Obrist Martin K. , Perlík Michal , Rost Josep , Waldron Kaysandra , Wermelinger Beat , Weiß Ingmar , Żmihorski Michał , Leverkus Alexandro B. 
Published: September 2020

AbstractForests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 75 ± 7% (mean ± SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90% richness of its unique species, whereas retaining 50% of a naturally disturbed forest unlogged maintains 73 ± 12% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups.
Body fatness and mTOR pathway activation of breast cancer in the Women’s Circle of Health Study
Authors: Cheng Ting-Yuan David , Omilian Angela R. , Yao Song , Sanchez Pamela V. , Polk Latasia Z. , Zhang Weizhou , Datta Susmita , Bshara Wiam , Ondracek Rochelle Payne , Davis Warren , Liu Song , Hong Chi-Chen , Bandera Elisa V. , Khoury Thaer , Ambrosone Christine B. 
Published: September 2020

AbstractEnergy imbalance has an important role in breast cancer prognosis. Hyperactive mechanistic Target of Rapamycin (mTOR) pathway is associated with breast tumor growth, but the extent to which body fatness is associated with mTOR pathway activities in breast cancer is unclear. We performed immunostaining for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-p70S6K in tumor tissue from 590 women (464 African Americans/Blacks and 126 Whites) with newly diagnosed invasive breast cancer in the Women’s Circle of Health Study. Anthropometric measures were taken by study staff, and body composition was measured by bioelectrical impedance analysis. Linear regressions were used to estimate percent differences in protein expression between categories of body mass index (BMI), waist circumference, waist/hip ratio, fat mass, fat mass index, and percent body fat. We observed that BMI ≥ 35.0 vs. <25 kg/m2 was associated with 108.3% (95% CI = 16.9%–270.9%) and 101.8% (95% CI = 17.0%–248.8%) higher expression in p-mTOR and normalized p-mTOR, i.e., p-mTOR/mTOR, respectively. Quartiles 4 vs. 1 of waist/hip ratio was associated with 41.8% (95% CI = 5.81%–89.9%) higher mTOR expression. Similar associations were observed for the body fat measurements, particularly in patients with estrogen receptor-negative (ER−) tumors, but not in those with ER+ tumors, although the differences in associations were not significant. This tumor-based study found positive associations between body fatness and mTOR pathway activation, evident by a p-mTOR expression, in breast cancer. Our findings suggest that mTOR inhibition can be a treatment strategy to prevent the recurrence of these tumors in obese individuals.
Diagnostic utility of whole-genome sequencing for nephronophthisis
Authors: Larrue Romain , Chamley Paul , Bardyn Thomas , Lionet Arnaud , Gnemmi Viviane , Cauffiez Christelle , Glowacki François , Pottier Nicolas , Broly Franck 
Published: September 2020

AbstractNext-generation sequencing has revolutionized the molecular diagnosis of individuals affected by genetic kidney diseases. Indeed, rapid genetic testing in individuals with suspected inherited nephropathy has not only important implications for diagnosis and prognosis but also for genetic counseling. Nephronophthisis (NPHP) and related syndromes, a leading cause of end-stage renal failure, are autosomal recessive disorders characterized by the variable presentation and considerable locus heterogeneity with more than 90 genes described as single-gene causes. In this case report, we demonstrate the utility of whole-genome sequencing (WGS) for the molecular diagnosis of NPHP by identifying two putative disease-causing intronic mutations in the NPHP3 gene, including one deep intronic variant. We further show that both intronic variants, by affecting splicing, result in a truncated nephrocystin-3 protein. This study provides a framework for applying WGS as a first-line diagnostic tool for highly heterogeneous disease such as NPHP and further suggests that deep intronic variations are an important underestimated cause of monogenic disorders.
3D hindlimb joint mobility of the stem-archosaur Euparkeria capensis with implications for postural evolution within Archosauria
Authors: Demuth Oliver E. , Rayfield Emily J. , Hutchinson John R. 
Published: September 2020

AbstractTriassic archosaurs and stem-archosaurs show a remarkable disparity in their ankle and pelvis morphologies. However, the implications of these different morphologies for specific functions are still poorly understood. Here, we present the first quantitative analysis into the locomotor abilities of a stem-archosaur applying 3D modelling techniques. μCT scans of multiple specimens ofEuparkeria capensisenabled the reconstruction and three-dimensional articulation of the hindlimb. The joint mobility of the hindlimb was quantified in 3D to address previous qualitative hypotheses regarding the stance ofEuparkeria. Our range of motion analysis implies the potential for an erect posture, consistent with the hip morphology, allowing the femur to be fully adducted to position the feet beneath the body. A fully sprawling pose appears unlikely but a wide range of hip abduction remained feasible—the hip appears quite mobile. The oblique mesotarsal ankle joint inEuparkeriaimplies, however, a more abducted hindlimb. This is consistent with a mosaic of ancestral and derived osteological characters in the hindlimb, and might suggest a moderately adducted posture forEuparkeria. Our results support a single origin of a pillar-erect hip morphology, ancestral to Eucrocopoda that preceded later development of a hinge-like ankle joint and a more erect hindlimb posture.
Cooperation, social norm internalization, and hierarchical societies
Authors: Lozano Pablo , Gavrilets Sergey , Sánchez Angel 
Published: September 2020

AbstractMany animal and human societies exhibit hierarchical structures with different degrees of steepness. Some of these societies also show cooperative behavior, where cooperation means working together for a common benefit. However, there is an increasing evidence that rigidly enforced hierarchies lead to a decrease of cooperation in both human and non-human primates. In this work, we address this issue by means of an evolutionary agent-based model that incorporates fights as social interactions governing a dynamic ranking, communal work to produce a public good, and norm internalization, i.e. a process where acting according to a norm becomes a goal in itself. Our model also includes the perception of how much the individual is going to retain from her cooperative behavior in future interactions. The predictions of the model resemble the principal characteristics of human societies. When ranking is unconstrained, we observe a high concentration of agents in low scores, while a few ones climb up the social hierarchy and exploit the rest, with no norm internalization. If ranking is constrained, thus leading to bounded score differences between agents, individual positions in the ranking change more, and the typical structure shows a division of the society in upper and lower classes. In this case, we observe that there is a significant degree of norm internalization, supporting large fractions of the population cooperating in spite of the rank differences. Our main results are robust with respect to the model parameters and to the type of rank constraint. We thus provide a mechanism that can explain how hierarchy arises in initially egalitarian societies while keeping a large degree of cooperation.
Alteration of salivary microbiome in periodontitis with or without type-2 diabetes mellitus and metformin treatment
Authors: Sun Xiaoyu , Li Meihui , Xia Li , Fang Zhaohui , Yu Shenjun , Gao Jike , Feng Qiang , Yang Pishan 
Published: September 2020

AbstractWe aimed to explore the effects of type-2 diabetes mellitus (T2DM) and hypoglycemic therapy on the salivary microbiome in periodontitis patients and identify the potential salivary micro-biomarker for the early warning of T2DM. Saliva samples were collected from healthy individuals (Health), periodontitis patients (P), T2DM patients, periodontitis patients with T2DM (DAP), and DAP patients treated with Metformin (Met). Samples were determined by16S rRNA gene sequencing. 29 phyla, 322 genera, and 333 species of salivary microbiome were annotated. Compared to the Health group, the P and DAP group showed a significantly higher diversity of saliva microbiota, while the T2DM and Met group had no significant difference in microbial abundance but showed a trend of increasing diversity. Other than well-known periodontitis-inducing pathogens, the proportion of Prevotella copri, Alloprevotella rava, and Ralstonia pickettii, etc. were also significantly increased in periodontitis patients with or without T2DM. After effective glycemic control, the abundance of Prevotella copri, Alloprevotella rava, Ralstonia pickettii, etc. decreased in periodontitis patients with companion T2DM. The accuracies of the classification models in differentiating Health-vs.-P, DAP-vs.-P, and T2DM-vs.-P were 100%, 96.3%, and 98.1%, respectively. Hypoglycemic therapy could reconstruct the saliva microbiota and hence improve the localized conditions of diabetes patients with periodontitis.
An unusual type I ribosome-inactivating protein from Agrostemma githago L.
Authors: Weise Christoph , Schrot Achim , Wuerger Leonie T. D. , Adolf Jacob , Gilabert-Oriol Roger , Sama Simko , Melzig Matthias F. , Weng Alexander 
Published: September 2020

AbstractAgrostemma githago L. (corn cockle) is an herbaceous plant mainly growing in Europe. The seeds of the corn cockle are toxic and poisonings were widespread in the past by consuming contaminated flour. The toxic principle of Agrostemma seeds was attributed to triterpenoid secondary metabolites. Indeed, this is in part true. However Agrostemma githago L. is also a producer of ribosome-inactivating proteins (RIPs). RIPs are N-glycosylases that inactivate the ribosomal RNA, a process leading to an irreversible inhibition of protein synthesis and subsequent cell death. A widely known RIP is ricin from Ricinus communis L., which was used as a bioweapon in the past. In this study we isolated agrostin, a 27 kDa RIP from the seeds of Agrostemma githago L., and determined its full sequence. The toxicity of native agrostin was investigated by impedance-based live cell imaging. By RNAseq we identified 7 additional RIPs (agrostins) in the transcriptome of the corn cockle. Agrostin was recombinantly expressed in E. coli and characterized by MALDI-TOF–MS and adenine releasing assay. This study provides for the first time a comprehensive analysis of ribosome-inactivating proteins in the corn cockle and complements the current knowledge about the toxic principles of the plant.