bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterocellular gene signatures reveal luminal-A breast cancer heterogeneity and differential therapeutic responses
Authors: Poudel Pawan , Nyamundanda Gift , Patil Yatish , Cheang Maggie Chon U , Sadanandam Anguraj 
Published: August 2019

AbstractBreast cancer is a highly heterogeneous disease. Although differences between intrinsic breast cancer subtypes have been well studied, heterogeneity within each subtype, especially luminal-A cancers, requires further interrogation to personalize disease management. Here, we applied well-characterized and cancer-associated heterocellular signatures representing stem, mesenchymal, stromal, immune, and epithelial cell types to breast cancer. This analysis stratified the luminal-A breast cancer samples into five subtypes with a majority of them enriched for a subtype (stem-like) that has increased stem and stromal cell gene signatures, representing potential luminal progenitor origin. The enrichment of immune checkpoint genes and other immune cell types in two (including stem-like) of the five heterocellular subtypes of luminal-A tumors suggest their potential response to immunotherapy. These immune-enriched subtypes of luminal-A tumors (containing only estrogen receptor positive samples) showed good or intermediate prognosis along with the two other differentiated subtypes as assessed using recurrence-free and distant metastasis-free patient survival outcomes. On the other hand, a partially differentiated subtype of luminal-A breast cancer with transit-amplifying colon-crypt characteristics showed poor prognosis. Furthermore, published luminal-A subtypes associated with specific somatic copy number alterations and mutations shared similar cellular and mutational characteristics to colorectal cancer subtypes where the heterocellular signatures were derived. These heterocellular subtypes reveal transcriptome and cell-type based heterogeneity of luminal-A and other breast cancer subtypes that may be useful for additional understanding of the cancer type and potential patient stratification and personalized medicine.
Essential ion binding residues for Na+ flow in stator complex of the Vibrio flagellar motor
Authors: Onoue Yasuhiro , Iwaki Masayo , Shinobu Ai , Nishihara Yasutaka , Iwatsuki Hiroto , Terashima Hiroyuki , Kitao Akio , Kandori Hideki , Homma Michio 
Published: August 2019

AbstractThe bacterial flagellar motor is a unique supramolecular complex which converts ion flow into rotational force. Many biological devices mainly use two types of ions, proton and sodium ion. This is probably because of the fact that life originated in seawater, which is rich in protons and sodium ions. The polar flagellar motor in Vibrio is coupled with sodium ion and the energy converting unit of the motor is composed of two membrane proteins, PomA and PomB. It has been shown that the ion binding residue essential for ion transduction is the conserved aspartic acid residue (PomB-D24) in the PomB transmembrane region. To reveal the mechanism of ion selectivity, we identified essential residues, PomA-T158 and PomA-T186, other than PomB-D24, in the Na+-driven flagellar motor. It has been shown that the side chain of threonine contacts Na+ in Na+-coupled transporters. We monitored the Na+-binding specific structural changes using ATR-FTIR spectroscopy. The signals were abolished in PomA-T158A and -T186A, as well as in PomB-D24N. Molecular dynamics simulations further confirmed the strong binding of Na+ to D24 and showed that T158A and T186A hindered the Na+ binding and transportation. The data indicate that two threonine residues (PomA-T158 and PomA-T186), together with PomB-D24, are important for Na+ conduction in the Vibrio flagellar motor. The results contribute to clarify the mechanism of ion recognition and conversion of ion flow into mechanical force.
Dynamics from elastic neutron-scattering via direct measurement of the running time-integral of the van Hove distribution function
Authors: Benedetto Antonio , Kearley Gordon J. 
Published: August 2019

AbstractWe present a new neutron-scattering approach to access the van Hove distribution function directly in the time domain, I(t), which reflects the system dynamics. Currently, I(t) is essentially determined from neutron energy-exchange. Our method consists of the straightforward measurement of the running time-integral of I(t), by computing the portion of scattered neutrons corresponding to species at rest within a time t, (conceptually elastic scattering). Previous attempts failed to recognise this connection. Starting from a theoretical standpoint, a practical realisation is assessed via numerical methods and an instrument simulation.
X-ray Crystallographic Structure and Oligomerization of Gloeobacter Rhodopsin
Authors: Morizumi Takefumi , Ou Wei-Lin , Van Eps Ned , Inoue Keiichi , Kandori Hideki , Brown Leonid S. , Ernst Oliver P. 
Published: August 2019

AbstractGloeobacter rhodopsin (GR) is a cyanobacterial proton pump which can be potentially applied to optogenetics. We solved the crystal structure of GR and found that it has overall similarity to the homologous proton pump from Salinibacter ruber, xanthorhodopsin (XR). We identified distinct structural characteristics of GR’s hydrogen bonding network in the transmembrane domain as well as the displacement of extracellular sides of the transmembrane helices relative to those of XR. Employing Raman spectroscopy and flash-photolysis, we found that GR in the crystals exists in a state which displays retinal conformation and photochemical cycle similar to the functional form observed in lipids. Based on the crystal structure of GR, we selected a site for spin labeling to determine GR’s oligomerization state using double electron–electron resonance (DEER) spectroscopy and demonstrated the pH-dependent pentamer formation of GR. Determination of the structure of GR as well as its pentamerizing propensity enabled us to reveal the role of structural motifs (extended helices, 3-omega motif and flipped B-C loop) commonly found among light-driven bacterial pumps in oligomer formation. Here we propose a new concept to classify these pumps based on the relationship between their oligomerization propensities and these structural determinants.
Multisensory learning between odor and sound enhances beta oscillations
Authors: Gnaedinger A. , Gurden H. , Gourévitch B. , Martin C. 
Published: August 2019

AbstractMultisensory interactions are essential to make sense of the environment by transforming the mosaic of sensory inputs received by the organism into a unified perception. Brain rhythms allow coherent processing within areas or between distant brain regions and could thus be instrumental in functionally connecting remote brain areas in the context of multisensory interactions. Still, odor and sound processing relate to two sensory systems with specific anatomofunctional characteristics. How does the brain handle their association? Rats were challenged to discriminate between unisensory stimulation (odor or sound) and the multisensory combination of both. During learning, we observed a progressive establishment of high power beta oscillations (15–35 Hz) spanning on the olfactory bulb, the piriform cortex and the perirhinal cortex, but not the primary auditory cortex. In the piriform cortex, beta oscillations power was higher in the multisensory condition compared to the presentation of the odor alone. Furthermore, in the olfactory structures, the sound alone was able to elicit a beta oscillatory response. These findings emphasize the functional differences between olfactory and auditory cortices and reveal that beta oscillations contribute to the memory formation of the multisensory association.
Keratin 17 identifies the most lethal molecular subtype of pancreatic cancer
Authors: Roa-Peña Lucia , Leiton Cindy V. , Babu Sruthi , Pan Chun-Hao , Vanner Elizabeth A. , Akalin Ali , Bandovic Jela , Moffitt Richard A. , Shroyer Kenneth R. , Escobar-Hoyos Luisa F. 
Published: August 2019

AbstractAlthough the overall five-year survival of patients with pancreatic ductal adenocarcinoma (PDAC) is dismal, there are survival differences between cases with clinically and pathologically indistinguishable characteristics, suggesting that there are uncharacterized properties that drive tumor progression. Recent mRNA sequencing studies reported gene-expression signatures that define PDAC molecular subtypes that correlate with differences in survival. We previously identified Keratin 17 (K17) as a negative prognostic biomarker in other cancer types. Here, we set out to determine if K17 is as accurate as molecular subtyping of PDAC to identify patients with the shortest survival. K17 mRNA was analyzed in two independent PDAC cohorts for discovery (n = 124) and validation (n = 145). Immunohistochemical localization and scoring of K17 immunohistochemistry (IHC) was performed in a third independent cohort (n = 74). Kaplan-Meier and Cox proportional-hazard regression models were analyzed to determine cancer specific survival differences in low vs. high mRNA K17 expressing cases. We established that K17 expression in PDACs defines the most aggressive form of the disease. By using Cox proportional hazard ratio, we found that increased expression of K17 at the IHC level is also associated with decreased survival of PDAC patients. Additionally, within PDACs of advanced stage and negative surgical margins, K17 at both mRNA and IHC level is sufficient to identify the subgroup with the shortest survival. These results identify K17 as a novel negative prognostic biomarker that could inform patient management decisions.
Reversibility of Age-related Oxidized Free NADH Redox States in Alzheimer’s Disease Neurons by Imposed External Cys/CySS Redox Shifts
Authors: Dong Yue , Sameni Sara , Digman Michelle A. , Brewer Gregory J. 
Published: August 2019

AbstractRedox systems including extracellular cysteine/cystine (Cys/CySS), intracellular glutathione/oxidized glutathione (GSH/GSSG) and nicotinamide adenine dinucleotide reduced/oxidized forms (NADH/NAD+) are critical for maintaining redox homeostasis. Aging as a major risk factor for Alzheimer’s disease (AD) is associated with oxidative shifts, decreases in anti-oxidant protection and dysfunction of mitochondria. Here, we examined the flexibility of mitochondrial-specific free NADH in live neurons from non-transgenic (NTg) or triple transgenic AD-like mice (3xTg-AD) of different ages under an imposed extracellular Cys/CySS oxidative or reductive condition. We used phasor fluorescence lifetime imaging microscopy (FLIM) to distinguish free and bound NADH in mitochondria, nuclei and cytoplasm. Under an external oxidative stress, a lower capacity for maintaining mitochondrial free NADH levels was found in old compared to young neurons and a further decline with genetic load. Remarkably, an imposed Cys/CySS reductive state rejuvenated the mitochondrial free NADH levels of old NTg neurons by 71% and old 3xTg-AD neurons by 89% to levels corresponding to the young neurons. Using FLIM as a non-invasive approach, we were able to measure the reversibility of aging subcellular free NADH levels in live neurons. Our results suggest a potential reductive treatment to reverse the loss of free NADH in old and Alzheimer’s neurons.
Drift-diffusion explains response variability and capacity for tracking objects
Authors: Daneshi Asieh , Azarnoush Hamed , Towhidkhah Farzad , Gohari Amin , Ghazizadeh Ali 
Published: August 2019

AbstractBeing able to track objects that surround us is key for planning actions in dynamic environments. However, rigorous cognitive models for tracking of one or more objects are currently lacking. In this study, we asked human subjects to judge the time to contact (TTC) a finish line for one or two objects that became invisible shortly after moving. We showed that the pattern of subject responses had an error variance best explained by an inverse Gaussian distribution and consistent with the output of a biased drift-diffusion model. Furthermore, we demonstrated that the pattern of errors made when tracking two objects showed a level of dependence that was consistent with subjects using a single decision variable for reporting the TTC for two objects. This finding reveals a serious limitation in the capacity for tracking multiple objects resulting in error propagation between objects. Apart from explaining our own data, our approach helps interpret previous findings such as asymmetric interference when tracking multiple objects.
Generalised thresholding of hidden variable network models with scale-free property
Authors: Balogh Sámuel G. , Pollner Péter , Palla Gergely 
Published: August 2019

AbstractThe hidden variable formalism (based on the assumption of some intrinsic node parameters) turned out to be a remarkably efficient and powerful approach in describing and analyzing the topology of complex networks. Owing to one of its most advantageous property - namely proven to be able to reproduce a wide range of different degree distribution forms - it has become a standard tool for generating networks having the scale-free property. One of the most intensively studied version of this model is based on a thresholding mechanism of the exponentially distributed hidden variables associated to the nodes (intrinsic vertex weights), which give rise to the emergence of a scale-free network where the degree distribution p(k) ~ k−γ is decaying with an exponent of γ = 2. Here we propose a generalization and modification of this model by extending the set of connection probabilities and hidden variable distributions that lead to the aforementioned degree distribution, and analyze the conditions leading to the above behavior analytically. In addition, we propose a relaxation of the hard threshold in the connection probabilities, which opens up the possibility for obtaining sparse scale free networks with arbitrary scaling exponent.
Towards integrated metatronics: a holistic approach on precise optical and electrical properties of Indium Tin Oxide
Authors: Gui Yaliang , Miscuglio Mario , Ma Zhizhen , Tahersima Mohammad H. , Sun Shuai , Amin Rubab , Dalir Hamed , Sorger Volker J. 
Published: August 2019

AbstractThe class of transparent conductive oxides includes the material indium tin oxide (ITO) and has become a widely used material of modern every-day life such as in touch screens of smart phones and watches, but also used as an optically transparent low electrically-resistive contract in the photovoltaics industry. More recently ITO has shown epsilon-near-zero (ENZ) behavior in the telecommunication frequency band enabling both strong index modulation and other optically-exotic applications such as metatronics. However, the ability to precisely obtain targeted electrical and optical material properties in ITO is still challenging due to complex intrinsic effects in ITO and as such no integrated metatronic platform has been demonstrated to-date. Here we deliver an extensive and accurate description process parameter of RF-sputtering, showing a holistic control of the quality of ITO thin films in the visible and particularly near-infrared spectral region. We are able to custom-engineer the ENZ point across the telecommunication band by explicitly controlling the sputtering process conditions. Exploiting this control, we design a functional sub-wavelength-scale filter based on lumped circuit-elements, towards the realization of integrated metatronic devices and circuits.
Fine microstructure formation in steel under ultrafast heating
Authors: Yonemura Mitsuharu , Nishibata Hitomi , Nishiura Tomohiro , Ooura Natsumi , Yoshimoto Yuki , Fujiwara Kazuki , Kawano Kaori , Terai Tomoyuki , Inubushi Yuichi , Inoue Ichiro , Tono Kensuke , Yabashi Makina 
Published: August 2019

AbstractIn this study, phase transformation kinetics was directly evaluated using a femtosecond X-ray diffraction technique for operand measurements of the dislocation densities and carbon concentrations in Fe-0.1mass%C martensitic steel. To identify the reverse transformation mechanism from α′ to γ, we used an X-ray free-electron laser and ultrafast heating. A maximum heating rate of 104 °C/s, which is sufficient to avoid diffusive reversion, was achieved, and the reverse transformation during ultrafast heating was successfully observed. Our results demonstrated that a fine microstructure formed because of a phase transformation in which the dislocation density and carbon concentrations remained high owing to ultrafast heating. Fe–C martensitic steels were also found to undergo a massive reverse transformation during ultrafast heating. The formation of a fine microstructure by a simple manufacturing process, without rare elements such as Ti, Nb, or Mo, can be expected. This study will help further the development of functional steels.
Quantitative Profiling of Oncometabolites in Frozen and Formalin-Fixed Paraffin-Embedded Tissue Specimens by Liquid Chromatography Coupled with Tandem Mass Spectrometry
Authors: Bao Xun , Wu Jianmei , Shuch Brian , LoRusso Patricia , Bindra Ranjit S. , Li Jing 
Published: August 2019

AbstractGiven the implications of oncometabolites [succinate, fumarate, and 2-hydroxyglutarate (2HG)] in cancer pathogenesis and therapeutics, quantitative determination of their tissue levels has significant diagnostic, prognostic, and therapeutic values. Here, we developed and validated a multiplex liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) platform that allows simultaneous determination of oncometabolites (including succinate, fumarate and total 2HG) and other tricarboxylic acid cycle metabolites (α-ketoglutarate, malic acid, and glutamate) in frozen and FFPE tissues specimens. In addition, by employing chiral derivatization in the sample preparation, the platform enabled separation and determination of 2HG enantiomers (D- and L-2HG) in frozen and FFPE tissues. Isotope-labeled internal standard method was used for the quantitation. Linear calibration curve ranges in aqueous solution were 0.02–10, 0.2–100, 0.002–10, and 0.002–5 µM for succinate, fumarate, total 2HG, and D/L-2HG, respectively. Intra- and inter-day precision and accuracy for individual oncometabolites were within the generally accepted criteria for bioanalytical method validation (<15%). The recovery of spiked individual oncometabolites from pooled homogenate of FFPE or frozen tissue ranged 86–112%. Method validation indicated the technical feasibility, reliability and reproducibility of the platform. Oncometabolites were notably lost during the routine FFPE process. The ratios of succinate to glutamate, fumarate to α-ketoglutarate, 2HG to glutamate, and D-2HG to L-2HG were reliable surrogate measurements for the detection of altered levels of oncometabolites in FFPE specimens. Our study laid a foundation for the utility of archival FFPE specimens for oncometabolite profiling as a valid technique in clinical research and routine medical care.
Revisiting the optical bandgap of semiconductors and the proposal of a unified methodology to its determination
Authors: Zanatta A. R. 
Published: August 2019

AbstractAlong the last two centuries, the story of semiconductor materials ranged from a mix of disbelief and frustration to one of the most successful technological achievements ever seen. Such a progress comprised the development of materials and models that, allied to the knowledge provided by spectroscopic techniques, resulted in the (nowadays) omnipresent electronic gadgets. Within this context, optically-based methods were of special importance since, amongst others, they presented details about the electronic states and energy bandgap Egapof semiconductors which, ultimately, decided about their application in devices. Stimulated by these aspects, this work investigated the semiconductors silicon, germanium, and gallium-arsenide in the crystalline (bulk and powder) and amorphous (film) forms. The detailed analysis of the experimental results indicates that accurate Egapvalues can be obtained by fitting a sigmoid (Boltzmann) function to their corresponding optical absorption spectra. The method is straightforward and, contrary to the traditional approaches to determine Egap, it is exempt from errors due to experimental spectra acquisition and data processing. Additionally, it complies with the requirements of direct, indirect, and amorphous bandgap semiconductors, and it is able to probe the (dis)order of the material as well. In view of these characteristics, a new−unified methodology based on the fitting of the absorption spectrum with a Boltzmann function is being proposed to efficiently determine the optical bandgap of semiconductor materials.
3D-printable portable open-source platform for low-cost lens-less holographic cellular imaging
Authors: Amann Stephan , Witzleben Max von , Breuer Stefan 
Published: August 2019

AbstractDigital holographic microscopy is an emerging, potentially low-cost alternative to conventional light microscopy for micro-object imaging on earth, underwater and in space. Immediate access to micron-scale objects however requires a well-balanced system design and sophisticated reconstruction algorithms, that are commercially available, however not accessible cost-efficiently. Here, we present an open-source implementation of a lens-less digital inline holographic microscope platform, based on off-the-shelf optical, electronic and mechanical components, costing less than $190. It employs a Blu-Ray semiconductor-laser-pickup or a light-emitting-diode, a pinhole, a 3D-printed housing consisting of 3 parts and a single-board portable computer and camera with an open-source implementation of the Fresnel-Kirchhoff routine. We demonstrate 1.55 μm spatial resolution by laser-pickup and 3.91 μm by the light-emitting-diode source. The housing and mechanical components are 3D printed. Both printer and reconstruction software source codes are open. The light-weight microscope allows to image label-free micro-spheres of 6.5 μm diameter, human red-blood-cells of about 8 μm diameter as well as fast-growing plant Nicotiana-tabacum-BY-2 suspension cells with 50 μm sizes. The imaging capability is validated by imaging-contrast quantification involving a standardized test target. The presented 3D-printable portable open-source platform represents a fully-open design, low-cost modular and versatile imaging-solution for use in high- and low-resource areas of the world.