bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body Wave Speed Structure of Eastern North America
Authors: Savage Brian 
Published: November 2020

AbstractThe eastern, passive margin of the North American continent is more heterogeneous than originally envisioned. Imaged by teleseismic body wave arrivals, both compressional Vp and shear Vsh, the lithospheric mantle of the stable, eastern North America contains rapid and large wave speed variations from the fast, older interior toward the slower, margin structures along the continental edge. At multiple regions at the continental edge, wave speeds indicate the presence of a small amount of melt, <1%–2%. Melt assessments were computed using a suite of mineralogical/petrological models to convert Vp and Vsh into absolute temperatures and melt fraction. Moreover, along the Atlantic margin, wave speeds are lower than expected for a previously rifted margin. Within the continent interior, wave speeds in the mantle lithosphere vary spatially at wavelengths, suggesting strong compositional and mineralogical influence likely a result of later stage alteration from volatile rich fluids.
A New Ensemble‐Based Approach to Correct the Systematic Ocean Temperature Bias of CAS‐ESM‐C to Improve Its Simulation and Data Assimilation Abilities
Authors: Du Mengjiao , Zheng Fei , Zhu Jiang , Lin Renping , Yang Haipeng , Chen Quanliang 
Published: November 2020

AbstractOver the past several decades, many efforts have been devoted to increasing the simulation performance of climate models, but significant biases remain that hinder the performance of coupled systems. Hence, bias correction is regarded not only as a useful tool for improving climate simulations but also as an important step before data assimilation, which depends on the hypothesis of unbiasedness. In this study, using sea temperature climatological data, a new ensemble‐based approach is proposed for correcting the biases of the sea temperature in CAS‐ESM‐C. Through analyzing the results of the proposed bias correction method with various intensities and time windows, its performance in suppressing the simulation biases of ocean fields is evaluated. The simulation biases of atmospheric variables are also reduced via air‐sea interactions, which will improve the ocean simulation performance. Additional benefits can be realized by applying the bias correction method. For example, a superior simulation of climate variabilities in a coupled model, such as ENSO (El Niño‐Southern Oscillation), is realized due to the improvement of climatological fields. The ability to assimilate various ocean observations is also significantly improved with a better background mean state.
Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients
Authors: Angioni Roberta , Sánchez-Rodríguez Ricardo , Munari Fabio , Bertoldi Nicole , Arcidiacono Diletta , Cavinato Silvia , Marturano Davide , Zaramella Alice , Realdon Stefano , Cattelan Annamaria , Viola Antonella , Molon Barbara 
Published: November 2020

AbstractA global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases1. Age represents a key factor in COVID-19 morbidity and mortality2. Understanding age-associated immune signatures of patients are therefore important to identify preventive and therapeutic strategies. In this study, we investigated the immune profile of COVID-19 hospitalized patients identifying a distinctive age-dependent immune signature associated with disease severity. Indeed, defined circulating factors - CXCL8, IL-10, IL-15, IL-27, and TNF-α - positively correlate with older age, longer hospitalization, and a more severe form of the disease and may thus represent the leading signature in critical COVID-19 patients.
SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism
Authors: Polak Anna , Bialopiotrowicz Emilia , Krzymieniewska Beata , Wozniak Jolanta , Stojak Marta , Cybulska Magdalena , Kaniuga Ewelina , Mikula Michał , Jablonska Ewa , Gorniak Patryk , Noyszewska-Kania Monika , Szydlowski Maciej , Piechna Karolina , Piwocka Katarzyna , Bugajski Lukasz , Lech-Maranda Ewa , Barankiewicz Joanna , Kolkowska-Lesniak Agnieszka , Patkowska Elzbieta , Glodkowska-Mrowka Eliza , Baran Natalia , Juszczynski Przemyslaw 
Published: November 2020

AbstractSpleen tyrosine kinase (SYK) is an important oncogene and signaling mediator activated by cell surface receptors crucial for acute myeloid leukemia (AML) maintenance and progression. Genetic or pharmacologic inhibition of SYK in AML cells leads to increased differentiation, reduced proliferation, and cellular apoptosis. Herein, we addressed the consequences of SYK inhibition to leukemia stem-cell (LSC) function and assessed SYK-associated pathways in AML cell biology. Using gain-of-function MEK kinase mutant and constitutively active STAT5A, we demonstrate that R406, the active metabolite of a small-molecule SYK inhibitor fostamatinib, induces differentiation and blocks clonogenic potential of AML cells through the MEK/ERK1/2 pathway and STAT5A transcription factor, respectively. Pharmacological inhibition of SYK with R406 reduced LSC compartment defined as CD34+CD38−CD123+ and CD34+CD38−CD25+ in vitro, and decreased viability of LSCs identified by a low abundance of reactive oxygen species. Primary leukemic blasts treated ex vivo with R406 exhibited lower engraftment potential when xenotransplanted to immunodeficient NSG/J mice. Mechanistically, these effects are mediated by disturbed mitochondrial biogenesis and suppression of oxidative metabolism (OXPHOS) in LSCs. These mechanisms appear to be partially dependent on inhibition of STAT5 and its target gene MYC, a well-defined inducer of mitochondrial biogenesis. In addition, inhibition of SYK increases the sensitivity of LSCs to cytarabine (AraC), a standard of AML induction therapy. Taken together, our findings indicate that SYK fosters OXPHOS and participates in metabolic reprogramming of AML LSCs in a mechanism that at least partially involves STAT5, and that SYK inhibition targets LSCs in AML. Since active SYK is expressed in a majority of AML patients and confers inferior prognosis, the combination of SYK inhibitors with standard chemotherapeutics such as AraC constitutes a new therapeutic modality that should be evaluated in future clinical trials.
Surface-controlled reversal of the selectivity of halogen bonds
Authors: Tschakert Jalmar , Zhong Qigang , Martin-Jimenez Daniel , Carracedo-Cosme Jaime , Romero-Muñiz Carlos , Henkel Pascal , Schlöder Tobias , Ahles Sebastian , Mollenhauer Doreen , Wegner Hermann A. , Pou Pablo , Pérez Rubén , Schirmeisen André , Ebeling Daniel 
Published: November 2020

AbstractIntermolecular halogen bonds are ideally suited for designing new molecular assemblies because of their strong directionality and the possibility of tuning the interactions by using different types of halogens or molecular moieties. Due to these unique properties of the halogen bonds, numerous areas of application have recently been identified and are still emerging. Here, we present an approach for controlling the 2D self-assembly process of organic molecules by adsorption to reactive vs. inert metal surfaces. Therewith, the order of halogen bond strengths that is known from gas phase or liquids can be reversed. Our approach relies on adjusting the molecular charge distribution, i.e., the σ-hole, by molecule-substrate interactions. The polarizability of the halogen and the reactiveness of the metal substrate are serving as control parameters. Our results establish the surface as a control knob for tuning molecular assemblies by reversing the selectivity of bonding sites, which is interesting for future applications.
Solid cyclooctatetraene-based triplet quencher demonstrating excellent suppression of singlet–triplet annihilation in optical and electrical excitation
Authors: Mai Van T. N. , Ahmad Viqar , Mamada Masashi , Fukunaga Toshiya , Shukla Atul , Sobus Jan , Krishnan Gowri , Moore Evan G. , Andersson Gunther G. , Adachi Chihaya , Namdas Ebinazar B. , Lo Shih-Chun 
Published: November 2020

AbstractTriplet excitons have been identified as the major obstacle to the realisation of organic laser diodes, as accumulation of triplet excitons leads to significant losses under continuous wave (CW) operation and/or electrical excitation. Here, we report the design and synthesis of a solid-state organic triplet quencher, as well as in-depth studies of its dispersion into a solution processable bis-stilbene-based laser dye. By blending the laser dye with 20 wt% of the quencher, negligible effects on the ASE thresholds, but a complete suppression of singlet–triplet annihilation (STA) and a 20-fold increase in excited-state photostability of the laser dye under CW excitation, were achieved. We used small-area OLEDs (0.2 mm2) to demonstrate efficient STA suppression by the quencher in the nanosecond range, supported by simulations to provide insights into the observed STA quenching under electrical excitation. The results demonstrate excellent triplet quenching ability under both optical and electrical excitations in the nanosecond range, coupled with excellent solution processability.
Tp63-expressing adult epithelial stem cells cross lineages boundaries revealing latent hairy skin competence
Authors: Claudinot Stéphanie , Sakabe Jun-Ichi , Oshima Hideo , Gonneau Christèle , Mitsiadis Thimios , Littman Daniel , Bonfanti Paola , Martens Geert , Nicolas Michael , Rochat Ariane , Barrandon Yann 
Published: November 2020

AbstractThe formation of hair follicles, a landmark of mammals, requires complex mesenchymal–epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo. Here, we demonstrate that epithelial stem cells of non-skin origin (e.g. that of cornea, oesophagus, vagina, bladder, prostate) that express the transcription factor Tp63, a master gene for the development of epidermis and its appendages, can respond to skin morphogenetic signals. When exposed to a newborn skin microenvironment, these cells express hair-follicle lineage markers and contribute to hair follicles, sebaceous glands and/or epidermis renewal. Our results demonstrate that lineage restriction is not immutable and support the notion that all Tp63-expressing epithelial stem cells, independently of their embryonic origin, have latent skin competence explaining why aberrant hair follicles or sebaceous glands are sometimes observed in non-skin tissues (e.g. in cornea, vagina or thymus).
Identification of phenothiazine derivatives as UHM-binding inhibitors of early spliceosome assembly
Authors: Jagtap Pravin Kumar Ankush , Kubelka Tomáš , Soni Komal , Will Cindy L. , Garg Divita , Sippel Claudia , Kapp Tobias G. , Potukuchi Harish Kumar , Schorpp Kenji , Hadian Kamyar , Kessler Horst , Lührmann Reinhard , Hausch Felix , Bach Thorsten , Sattler Michael 
Published: November 2020

AbstractInteractions between U2AF homology motifs (UHMs) and U2AF ligand motifs (ULMs) play a crucial role in early spliceosome assembly in eukaryotic gene regulation. UHM-ULM interactions mediate heterodimerization of the constitutive splicing factors U2AF65 and U2AF35 and between other splicing factors that regulate spliceosome assembly at the 3′ splice site, where UHM domains of alternative splicing factors, such as SPF45 and PUF60, contribute to alternative splicing regulation. Here, we performed high-throughput screening using fluorescence polarization assays with hit validation by NMR and identified phenothiazines as general inhibitors of UHM-ULM interactions. NMR studies show that these compounds occupy the tryptophan binding pocket of UHM domains. Co-crystal structures of the inhibitors with the PUF60 UHM domain and medicinal chemistry provide structure-activity-relationships and reveal functional groups important for binding. These inhibitors inhibit early spliceosome assembly on pre-mRNA substrates in vitro. Our data show that spliceosome assembly can be inhibited by targeting UHM-ULM interactions by small molecules, thus extending the toolkit of splicing modulators for structural and biochemical studies of the spliceosome and splicing regulation.
Suppressing the ferroelectric switching barrier in hybrid improper ferroelectrics
Authors: Li Shutong , Birol Turan 
Published: November 2020

AbstractIntegration of ferroelectric materials into novel technological applications requires low coercive field materials, and consequently, design strategies to reduce the ferroelectric switching barriers. In this first principles study, we show that biaxial strain, which has a strong effect on the ferroelectric ground states, can also be used to tune the switching barrier of hybrid improper ferroelectric Ruddlesden–Popper oxides. We identify the region of the strain-tolerance factor phase diagram where this intrinsic barrier is suppressed, and show that it can be explained in relation to strain-induced phase transitions to nonpolar phases.
Learning to encode cellular responses to systematic perturbations with deep generative models
Authors: Xue Yifan , Ding Michael Q. , Lu Xinghua 
Published: November 2020

AbstractCellular signaling systems play a vital role in maintaining homeostasis when a cell is exposed to different perturbations. Components of the systems are organized as hierarchical networks, and perturbing different components often leads to transcriptomic profiles that exhibit compositional statistical patterns. Mining such patterns to investigate how cellular signals are encoded is an important problem in systems biology, where artificial intelligence techniques can be of great assistance. Here, we investigated the capability of deep generative models (DGMs) to modeling signaling systems and learn representations of cellular states underlying transcriptomic responses to diverse perturbations. Specifically, we show that the variational autoencoder and the supervised vector-quantized variational autoencoder can accurately regenerate gene expression data in response to perturbagen treatments. The models can learn representations that reveal the relationships between different classes of perturbagens and enable mappings between drugs and their target genes. In summary, DGMs can adequately learn and depict how cellular signals are encoded. The resulting representations have broad applications, demonstrating the power of artificial intelligence in systems biology and precision medicine.
Mapping of subthalamic nucleus using microelectrode recordings during deep brain stimulation
Authors: Koirala Nabin , Serrano Lucas , Paschen Steffen , Falk Daniela , Anwar Abdul Rauf , Kuravi Pradeep , Deuschl Günther , Groppa Sergiu , Muthuraman Muthuraman 
Published: November 2020

AbstractAlongside stereotactic magnetic resonance imaging, microelectrode recording (MER) is frequently used during the deep brain stimulation (DBS) surgery for optimal target localization. The aim of this study is to optimize subthalamic nucleus (STN) mapping using MER analytical patterns. 16 patients underwent bilateral STN-DBS. MER was performed simultaneously for 5 microelectrodes in a setting of Ben’s-gun pattern in awake patients. Using spikes and background activity several different parameters and their spectral estimates in various frequency bands including low frequency (2–7 Hz), Alpha (8–12 Hz), Beta (sub-divided as Low_Beta (13–20 Hz) and High_Beta (21–30 Hz)) and Gamma (31 to 49 Hz) were computed. The optimal STN lead placement with the most optimal clinical effect/side-effect ratio accorded to the maximum spike rate in 85% of the implantation. Mean amplitude of background activity in the low beta frequency range was corresponding to right depth in 85% and right location in 94% of the implantation respectively. MER can be used for STN mapping and intraoperative decisions for the implantation of DBS electrode leads with a high accuracy. Spiking and background activity in the beta range are the most promising independent parameters for the delimitation of the proper anatomical site.
Functional redundancy of Burkholderia pseudomallei phospholipase C enzymes and their role in virulence
Authors: Srinon Varintip , Withatanung Patoo , Chaiwattanarungruengpaisan Somjit , Thongdee Metawee , Meethai Chatruthai , Stevens Joanne M. , Titball Richard W. , Korbsrisate Sunee 
Published: November 2020

AbstractPhospholipase C (PLC) enzymes are key virulence factors in several pathogenic bacteria. Burkholderia pseudomallei, the causative agent of melioidosis, possesses at least three plc genes (plc1, plc2 and plc3). We found that in culture medium plc1 gene expression increased with increasing pH, whilst expression of the plc3 gene was pH (4.5 to 9.0) independent. Expression of the plc2 gene was not detected in culture medium. All three plc genes were expressed during macrophage infection by B. pseudomallei K96243. Comparing B. pseudomallei wild-type with plc mutants revealed that plc2, plc12 or plc123 mutants showed reduced intracellular survival in macrophages and reduced plaque formation in HeLa cells. However, plc1 or plc3 mutants showed no significant differences in plaque formation compared to wild-type bacteria. These findings suggest that Plc2, but not Plc1 or Plc3 are required for infection of host cells. In Galleria mellonella, plc1, plc2 or plc3 mutants were not attenuated compared to the wild-type strain, but multiple plc mutants showed reduced virulence. These findings indicate functional redundancy of the B. pseudomallei phospholipases in virulence.
Ganoderma lucidum Rhodiola compound preparation prevent d-galactose-induced immune impairment and oxidative stress in aging rat model
Authors: Yuan Shuo , Yang Yong , Li Jiao , Tan Xiaoyu , Cao Yuying , Li Shaoheng , Hong Hee-Do , Liu Liping , Zhang Qinggao 
Published: November 2020

AbstractAging is an irreversible process. This research aims to study the anti-aging effects of GRCP, a compound preparation made byGanoderma lucidumandRhodiola rosen, in aging rats. Rats were subcutaneously injected with 400 mg/kg ofd-galactose daily, and aging could be induced after 8 weeks. The aging rats were treated with GRCP. This experiment was divided into 6 groups. Rats were randomly divided into the model group, positive control group, low-dose GRCP group (25 mg/kg body weight), medium-dose GRCP group (50 mg/kg body weight), and high-dose GRCP group (100 mg/kg body weight), healthy and normal rats were used as blank controls. After the end, the results show that the use of GRCP at a dose of 100 mg/kg is the best treatment for improving aging rats. Rats gained weight, spleen and thymus indexes, and splenocyte proliferation improved, and inflammatory cytokine levels decreased. Besides, biochemical indicators show that GRCP can improve the antioxidant enzyme activity and reduce the content of lipofuscin and TGF-β in aging rats (P < 0.05). GRCP can also inhibit the activation of the MyD88/NF-κB pathway in rat hippocampus. These results seem to suggest that GRCP can be used as a potential natural supplement or functional food to prevent aging.
Simple annealing process for producing unique one-dimensional fullerene crystal named fullerene finned-micropillar
Authors: Onishi Taku , Tsukamoto Takahiro , Oya Takahide 
Published: November 2020

AbstractWe propose a process for easily fabricating a unique one-dimensional fullerene crystal, i.e., a fullerene finned-micropillar (FFMP). To fabricate a one-dimensional fullerene crystal more easily than when using current processes, fullerene was first annealed at 1173 K for 1 h with an argon gas flow of 0.5 L/min. We then examined how the FFMP structure changed when the fabrication process conditions, such as temperature, annealing time, and argon gas flow rate, were varied. FFMPs can be prepared within a short time and may have the same electrical characteristics as other one-dimensional crystals, e.g., fullerene nanowhiskers, so they are expected to be very useful for field-effect transistors, organic photovoltaics, and so on in the near future.
Influence of the ECMO circuit on the concentration of nutritional supplements
Authors: Lindberg Beate Rikken , Videm Vibeke , Dahl Thorleif , Sørensen Gro , Fiane Arnt Eltvedt , Thiara Amrit Singh 
Published: November 2020

AbstractCirculating compounds such as drugs and nutritional components might adhere to the oxygenator fibers and tubing during ECMO support. This study evaluated the amount of nutritional supplements adsorbed to the ECMO circuit under controlled ex vivo conditions. Six identical ECMO circuits were primed with fresh human whole blood and maintained under physiological conditions at 36 °C for 24 h. A dose of nutritional supplement calculated for a 70 kg patient was added. 150 mL volume was drawn from the priming bag for control samples and kept under similar conditions. Blood samples were obtained at predetermined time points and analyzed for concentrations of vitamins, minerals, lipids, and proteins. Data were analyzed using mixed models with robust standard errors. No significant differences were found between the ECMO circuits and the controls for any of the measured variables: cobalamin, folate, vitamin A, glucose, minerals, HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides or total proteins. There was an initial decrease and then an increase in the concentration of cobalamin and folate. Vitamin A concentrations decreased in both groups over time. There was a decrease in concentration of glucose and an increased concentration of lactate dehydrogenase over time in both groups. There were no significant alterations in the concentrations of nutritional supplements in an ex vivo ECMO circuit compared to control samples. The time span of this study was limited, thus, clinical studies over a longer period of time are needed.
Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer
Authors: Roviello Giandomenico , Ramello Monica , Catalano Martina , D’Angelo Alberto , Conca Raffaele , Gasperoni Silvia , Dreoni Lorenzo , Petrioli Roberto , Ianza Anna , Nobili Stefania , Aieta Michele , Mini Enrico 
Published: November 2020

AbstractNeutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5–8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5–6) for patients with grade < 3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10–18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8–13) for patients with grade < 3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09–0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.