bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells
Authors: Koga Tomoyuki , Chaim Isaac A. , Benitez Jorge A. , Markmiller Sebastian , Parisian Alison D. , Hevner Robert F. , Turner Kristen M. , Hessenauer Florian M. , D’Antonio Matteo , Nguyen Nam-phuong D. , Saberi Shahram , Ma Jianhui , Miki Shunichiro , Boyer Antonia D. , Ravits John , Frazer Kelly A. , Bafna Vineet , Chen Clark C. , Mischel Paul S. , Yeo Gene W. , Furnari Frank B. 
Published: January 2020

AbstractMany cellular models aimed at elucidating cancer biology do not recapitulate pathobiology including tumor heterogeneity, an inherent feature of cancer that underlies treatment resistance. Here we introduce a cancer modeling paradigm using genetically engineered human pluripotent stem cells (hiPSCs) that captures authentic cancer pathobiology. Orthotopic engraftment of the neural progenitor cells derived from hiPSCs that have been genome-edited to contain tumor-associated genetic driver mutations revealed by The Cancer Genome Atlas project for glioblastoma (GBM) results in formation of high-grade gliomas. Similar to patient-derived GBM, these models harbor inter-tumor heterogeneity resembling different GBM molecular subtypes, intra-tumor heterogeneity, and extrachromosomal DNA amplification. Re-engraftment of these primary tumor neurospheres generates secondary tumors with features characteristic of patient samples and present mutation-dependent patterns of tumor evolution. These cancer avatar models provide a platform for comprehensive longitudinal assessment of human tumor development as governed by molecular subtype mutations and lineage-restricted differentiation.
Tunable anomalous Hall conductivity through volume-wise magnetic competition in a topological kagome magnet
Authors: Guguchia Z. , Verezhak J. A. T. , Gawryluk D. J. , Tsirkin S. S. , Yin J.-X. , Belopolski I. , Zhou H. , Simutis G. , Zhang S.-S. , Cochran T. A. , Chang G. , Pomjakushina E. , Keller L. , Skrzeczkowska Z. , Wang Q. , Lei H. C. , Khasanov R. , Amato A. , Jia S. , Neupert T. , Luetkens H. , Hasan M. Z. 
Published: January 2020

AbstractMagnetic topological phases of quantum matter are an emerging frontier in physics and material science. Along these lines, several kagome magnets have appeared as the most promising platforms. Here, we explore magnetic correlations in the kagome magnet Co3Sn2S2. Using muon spin-rotation, we present evidence for competing magnetic orders in the kagome lattice of this compound. Our results show that while the sample exhibits an out-of-plane ferromagnetic ground state, an in-plane antiferromagnetic state appears at temperatures above 90 K, eventually attaining a volume fraction of 80% around 170 K, before reaching a non-magnetic state. Strikingly, the reduction of the anomalous Hall conductivity (AHC) above 90 K linearly follows the disappearance of the volume fraction of the ferromagnetic state. We further show that the competition of these magnetic phases is tunable through applying either an external magnetic field or hydrostatic pressure. Our results taken together suggest the thermal and quantum tuning of Berry curvature induced AHC via external tuning of magnetic order.
The Red Sea Deep Water is a potent source of atmospheric ethane and propane
Authors: Bourtsoukidis E. , Pozzer A. , Sattler T. , Matthaios V. N. , Ernle L. , Edtbauer A. , Fischer H. , Könemann T. , Osipov S. , Paris J.-D. , Pfannerstill E. Y. , Stönner C. , Tadic I. , Walter D. , Wang N. , Lelieveld J. , Williams J. 
Published: January 2020

AbstractNon-methane hydrocarbons (NMHCs) such as ethane and propane are significant atmospheric pollutants and precursors of tropospheric ozone, while the Middle East is a global emission hotspot due to extensive oil and gas production. Here we compare in situ hydrocarbon measurements, performed around the Arabian Peninsula, with global model simulations that include current emission inventories (EDGAR) and state-of-the-art atmospheric circulation and chemistry mechanisms (EMAC model). While measurements of high mixing ratios over the Arabian Gulf are adequately simulated, strong underprediction by the model was found over the northern Red Sea. By examining the individual sources in the model and by utilizing air mass back-trajectory investigations and Positive Matrix Factorization (PMF) analysis, we deduce that Red Sea Deep Water (RSDW) is an unexpected, potent source of atmospheric NMHCs. This overlooked underwater source is comparable with total anthropogenic emissions from entire Middle Eastern countries, and significantly impacts the regional atmospheric chemistry.
Observation of persistent species temperature separation in inertial confinement fusion mixtures
Authors: Haines Brian M. , Shah R. C. , Smidt J. M. , Albright B. J. , Cardenas T. , Douglas M. R. , Forrest C. , Glebov V. Yu , Gunderson M. A. , Hamilton C. E. , Henderson K. C. , Kim Y. , Lee M. N. , Murphy T. J. , Oertel J. A. , Olson R. E. , Patterson B. M. , Randolph R. B. , Schmidt D. W. 
Published: January 2020

AbstractThe injection and mixing of contaminant mass into the fuel in inertial confinement fusion (ICF) implosions is a primary factor preventing ignition. ICF experiments have recently achieved an alpha-heating regime, in which fusion self-heating is the dominant source of yield, by reducing the susceptibility of implosions to instabilities that inject this mass. We report the results of unique separated reactants implosion experiments studying pre-mixed contaminant as well as detailed high-resolution three-dimensional simulations that are in good agreement with experiments. At conditions relevant to mixing regions in high-yield implosions, we observe persistent chunks of contaminant that do not achieve thermal equilibrium with the fuel throughout the burn phase. The assumption of thermal equilibrium is made in nearly all computational ICF modeling and methods used to infer levels of contaminant from experiments. We estimate that these methods may underestimate the amount of contaminant by a factor of two or more.
Scalable spin–photon entanglement by time-to-polarization conversion
Authors: Vasconcelos Rui , Reisenbauer Sarah , Salter Cameron , Wachter Georg , Wirtitsch Daniel , Schmiedmayer Jörg , Walther Philip , Trupke Michael 
Published: January 2020

AbstractThe realization of quantum networks and quantum computers relies on the scalable generation of entanglement, for which spin-photon interfaces are strong candidates. Current proposals to produce entangled-photon states with such platforms place stringent requirements on the physical properties of the photon emitters, limiting the range and performance of suitable physical systems. We propose a scalable protocol, which significantly reduces the constraints on the emitter. We use only a single optical transition and an asymmetric polarizing interferometer. This device converts the entanglement from the experimentally robust time basis via a path degree of freedom into a polarization basis, where quantum logic operations can be performed. The fundamental unit of the proposed protocol is realized experimentally in this work, using a nitrogen-vacancy center in diamond. This classically assisted protocol greatly widens the set of physical systems suited for scalable entangled-photon generation and enables performance enhancement of existing platforms.
A novel repetitive head impact exposure measurement tool differentiates player position in National Football League
Authors: Karton Clara , Blaine Hoshizaki T. , Gilchrist Michael D. 
Published: January 2020

AbstractAmerican-style football participation poses a high risk of repetitive head impact (RHI) exposure leading to acute and chronic brain injury. The complex nature of symptom expression, human predisposition, and neurological consequences of RHI limits our understanding of what constitutes as an injurious impact affecting the integrity of brain tissue. Video footage of professional football games was reviewed and documentation made of all head contact. Frequency of impact, tissue strain magnitude, and time interval between impacts was used to quantify RHI exposure, specific to player field position. Differences in exposure characteristics were found between eight different positions; where three unique profiles can be observed. Exposure profiles provide interpretation of the relationship between the traumatic event(s) and how tissue injury is manifested and expressed. This study illustrates and captures an objective measurement of RHI on the field, a critical component in guiding public policy and guidelines for managing exposure.
Sub-wavelength annular-slit-assisted superoscillatory lens for longitudinally-polarized super-resolution focusing
Authors: Kim Hyuntai , Rogers Edward T. F. 
Published: January 2020

AbstractA binary metallic superoscillatory lens assisted with annular subwavelength slits is proposed, which generates a longitudinally-polarized super-resolution focal point. The annular slits are designed to selectively transmit radially-polarized light. Simulations using the finite element method show a 0.24 λ focal spot with 21.8 dB of polarization purity and only 0.342 dB reduction in efficiency compared to a standard superoscillatory lens.
Ultra High Field fMRI of Human Superior Colliculi Activity during Affective Visual Processing
Authors: Wang Yuxi C. , Bianciardi Marta , Chanes Lorena , Satpute Ajay B. 
Published: January 2020

AbstractResearch on rodents and non-human primates has established the involvement of the superior colliculus in defensive behaviours and visual threat detection. The superior colliculus has been well-studied in humans for its functional roles in saccade and visual processing, but less is known about its involvement in affect. In standard functional MRI studies of the human superior colliculus, it is challenging to discern activity in the superior colliculus from activity in surrounding nuclei such as the periaqueductal gray due to technological and methodological limitations. Employing high-field strength (7 Tesla) fMRI techniques, this study imaged the superior colliculus at high (0.75 mm isotropic) resolution, which enabled isolation of the superior colliculus from other brainstem nuclei. Superior colliculus activation during emotionally aversive image viewing blocks was greater than that during neutral image viewing blocks. These findings suggest that the superior colliculus may play a role in shaping subjective emotional experiences in addition to its visuomotor functions, bridging the gap between affective research on humans and non-human animals.
Viscosity-adjustable grease matrices for serial nanocrystallography
Authors: Sugahara Michihiro , Motomura Koji , Suzuki Mamoru , Masuda Tetsuya , Joti Yasumasa , Numata Keiji , Tono Kensuke , Yabashi Makina , Ishikawa Tetsuya 
Published: January 2020

AbstractSerial femtosecond crystallography (SFX) has enabled determination of room temperature structures of proteins with minimum radiation damage. A highly viscous grease matrix acting as a crystal carrier for serial sample loading at a low flow rate of ~0.5 μl min−1 was introduced into the beam path of X-ray free-electron laser. This matrix makes it possible to determine the protein structure with a sample consumption of less than 1 mg of the protein. The viscosity of the matrix is an important factor in maintaining a continuous and stable sample column from a nozzle of a high viscosity micro-extrusion injector for serial sample loading. Using conventional commercial grease (an oil-based, viscous agent) with insufficient control of viscosity in a matrix often gives an unexpectedly low viscosity, providing an unstable sample stream, with effects such as curling of the stream. Adjustment of the grease viscosity is extremely difficult since the commercial grease contains unknown compounds, which may act as unexpected inhibitors of proteins. This study introduces two novel grease matrix carriers comprising known compounds with a viscosity higher than that of conventional greases, to determine the proteinase K structure from nano-/microcrystals.
Risk of active tuberculosis development in contacts exposed to infectious tuberculosis in congregate settings in Korea
Authors: Park Shin Young , Han Sunmi , Kim Young-Man , Kim Jieun , Lee Sodam , Yang Jiyeon , Kim Un-Na , Park Mi-sun 
Published: January 2020

AbstractContact investigation is an important and effective active case-finding strategy, but there is a lack of research on congregate settings in countries with an intermediate incidence. This study determined the incidence of and risk factors for tuberculosis (TB) development after exposure in congregate settings. This retrospective cohort study included 116,742 contacts identified during the investigation of 2,609 TB cases diagnosed from January to December 2015. We searched the Korean National Tuberculosis Surveillance System TB registry to identify contacts that developed active TB during follow-up until May 2018. During the mean observation period of 2.9 years, 499 of 116,742 contacts (0.4%) developed new active TB. From these contacts, 404 (81.0%) developed TB within 2 years after exposure. The 2-year Kaplan-Meier cumulative risk for TB was the highest in contacts aged ≥65 years [1%; 95% confidence interval (CI), 0.8–1.3]. Contacts with LTBI who completed chemoprophylaxis exhibited a lower risk of active TB development than those without chemoprophylaxis (adjusted hazard ratio, 0.16; 95% CI, 0.08–0.29). Aggressive contact investigation is effective for the early detection and prevention of TB in congregate settings. The risk of progression to active TB among contacts with LTBI can be minimised by the completion of chemoprophylaxis.
Advanced identification of global bioactivity hotspots via screening of the metabolic fingerprint of entire ecosystems
Authors: Mueller Constanze , Kremb Stephan , Gonsior Michael , Brack-Werner Ruth , Voolstra Christian R. , Schmitt-Kopplin Philippe 
Published: January 2020

AbstractNatural products (NP) are a valuable drug resource. However, NP-inspired drug leads are declining, among other reasons due to high re-discovery rates. We developed a conceptual framework using the metabolic fingerprint of entire ecosystems (MeE) to facilitate the discovery of global bioactivity hotspots. We assessed the MeE of 305 sites of diverse aquatic ecosystems, worldwide. All samples were tested for antiviral effects against the human immunodeficiency virus (HIV), followed by a comprehensive screening for cell-modulatory activity by High-Content Screening (HCS). We discovered a very strong HIV-1 inhibition mainly in samples taken from fjords with a strong terrestrial input. Multivariate data integration demonstrated an association of a set of polyphenols with specific biological alterations (endoplasmic reticulum, lysosomes, and NFkB) caused by these samples. Moreover, we found strong HIV-1 inhibition in one unrelated oceanic sample closely matching to HIV-1-inhibitory drugs on a cytological and a chemical level. Taken together, we demonstrate that even without physical purification, a sophisticated strategy of differential filtering, correlation analysis, and multivariate statistics can be employed to guide chemical analysis, to improve de-replication, and to identify ecosystems with promising characteristics as sources for NP discovery.
PreDBA: A heterogeneous ensemble approach for predicting protein-DNA binding affinity
Authors: Yang Wenyi , Deng Lei 
Published: January 2020

AbstractThe interaction between protein and DNA plays an essential function in various critical natural processes, like DNA replication, transcription, splicing, and repair. Studying the binding affinity of proteins to DNA helps to understand the recognition mechanism of protein-DNA complexes. Since there are still many limitations on the protein-DNA binding affinity data measured by experiments, accurate and reliable calculation methods are necessarily required. So we put forward a computational approach in this paper, called PreDBA, that can forecast protein-DNA binding affinity effectively by using heterogeneous ensemble models. One hundred protein-DNA complexes are manually collected from the related literature as a data set for protein-DNA binding affinity. Then, 52 sequence and structural features are obtained. Based on this, the correlation between these 52 characteristics and protein-DNA binding affinity is calculated. Furthermore, we found that the protein-DNA binding affinity is affected by the DNA molecule structure of the compound. We classify all protein-DNA compounds into five classifications based on the DNA structure related to the proteins that make up the protein-DNA complexes. In each group, a stacked heterogeneous ensemble model is constructed based on the obtained features. In the end, based on the binding affinity data set, we used the leave-one-out cross-validation to evaluate the proposed method comprehensively. In the five categories, the Pearson correlation coefficient values of our recommended method range from 0.735 to 0.926. We have demonstrated the advantages of the proposed method compared to other machine learning methods and currently existing protein-DNA binding affinity prediction approach.
Novel Alzheimer’s disease subtypes identified using a data and knowledge driven strategy
Authors: Mitelpunkt Alexis , Galili Tal , Kozlovski Tal , Bregman Noa , Shachar Netta , Markus-Kalish Mira , Benjamini Yoav 
Published: January 2020

AbstractThe population of adults with Alzheimer’s disease (AD) varies in needs and outcomes. The heterogeneity of current AD diagnostic subgroups impedes the use of data analytics in clinical trial design and translation of findings into improved care. The purpose of this project was to define more clinically-homogeneous groups of AD patients and link clinical characteristics with biological markers. We used an innovative big data analysis strategy, the 3C strategy, that incorporates medical knowledge into the data analysis process. A large set of preprocessed AD Neuroimaging Initiative (ADNI) data was analyzed with 3C. The data analysis yielded 6 new disease subtypes, which differ from the assigned diagnosis types and present different patterns of clinical measures and potential biomarkers. Two of the subtypes, “Anosognosia dementia” and “Insightful dementia”, differentiate between severe participants based on clinical characteristics and biomarkers. The “Uncompensated mild cognitive impairment (MCI)” subtype, demonstrates clinical, demographic and imaging differences from the “Affective MCI” subtype. Differences were also observed between the “Worried Well” and “Healthy” clusters. The use of data-driven analysis yielded sub-phenotypic clinical clusters that go beyond current diagnoses and are associated with biomarkers. Such homogenous sub-groups can potentially form the basis for enhancement of brain medicine research.
Assessing arid Inland Lake Watershed Area and Vegetation Response to Multiple Temporal Scales of Drought Across the Ebinur Lake Watershed
Authors: Zhang Junyong , Ding Jianli , Wu Pengfei , Tan Jiao , Huang Shuai , Teng Dexiong , Cao Xiaoyi , Wang Jingzhe , Chen Wenqian 
Published: January 2020

AbstractThe Ebinur Lake watershed is an important ecological barrier for environmental changes in the Junggar Basin in Xinjiang Uygur Autonomous Region (XUAR). Due to the tremendous changes in the underlying surface environment of the watershed in the past few decades, the watershed has become a typical region of ecological degradation. Drought affects the surface dynamics and characterizes the regional dry and wet environments, while the dynamic variation in lakes and vegetation are indicators of dynamic changes in land surfaces. Thus, a quantitative assessment of the response of lakes and vegetation to drought conditions at multiple temporal scales is critical for assessing the potential impacts of regional climate change on terrestrial ecosystems and ecological restoration. The standardized precipitation evapotranspiration index (SPEI), the spectral water index (NDWI) and the normalized difference vegetation index (NDVI) were used to analyse the evolution of drought, the variation in lake surface area and the sustainable variation in vegetation. Furthermore, we quantitatively evaluated the response patterns of vegetation to droughts of multiple temporal scales (1-, 3-, 6-, 12-, 24-month). The conclusions showed that (1) overall, the area of Ebinur Lake experienced drastic fluctuations, and the lake area has decreased significantly since 2003, with a dynamic area of 817.63 km2 in 2003 and 384.60 km2 in 2015, and the lake area had shrank severely. (2) The interannual variation of wet and dry changed alternately during the observation period, and persistent drought events occurred from 2006 to 2010 across the Ebinur Lake watershed. (3) The vegetation area of cultivated land expanded continuously across the watershed, and the grassland degraded severely. (4) The changes in lake surface area are significantly correlated with the inflow water volume (correlation coefficient = 0.64, P < 0.01). (5) The vegetation of different terrestrial ecosystems exhibited heterogeneous responses to multiple temporal scales of drought in different seasons. The percentage was 72.78% of the total area, which showed a correlation between vegetation and drought conditions during the growing season period, and there were more impacts of drought on vegetation, with values as high as 64.33% of the area in summer, than those in other seasons.
Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia
Authors: Hendrikse Natalie M. , Holmberg Larsson Albin , Svensson Gelius Stefan , Kuprin Sergei , Nordling Erik , Syrén Per-Olof 
Published: January 2020

AbstractPhenylalanine/tyrosine ammonia-lyases (PAL/TALs) have been approved by the FDA for treatment of phenylketonuria and may harbour potential for complementary treatment of hereditary tyrosinemia Type I. Herein, we explore ancestral sequence reconstruction as an enzyme engineering tool to enhance the therapeutic potential of PAL/TALs. We reconstructed putative ancestors from fungi and compared their catalytic activity and stability to two modern fungal PAL/TALs. Surprisingly, most putative ancestors could be expressed as functional tetramers in Escherichia coli and thus retained their ability to oligomerize. All ancestral enzymes displayed increased thermostability compared to both modern enzymes, however, the increase in thermostability was accompanied by a loss in catalytic turnover. One reconstructed ancestral enzyme in particular could be interesting for further drug development, as its ratio of specific activities is more favourable towards tyrosine and it is more thermostable than both modern enzymes. Moreover, long-term stability assessment showed that this variant retained substantially more activity after prolonged incubation at 25 °C and 37 °C, as well as an increased resistance to incubation at 60 °C. Both of these factors are indicative of an extended shelf-life of biopharmaceuticals. We believe that ancestral sequence reconstruction has potential for enhancing the properties of enzyme therapeutics, especially with respect to stability. This work further illustrates that resurrection of putative ancestral oligomeric proteins is feasible and provides insight into the extent of conservation of a functional oligomerization surface area from ancestor to modern enzyme.