bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stratification of TAD boundaries reveals preferential insulation of super-enhancers by strong boundaries
Authors: Gong Yixiao , Lazaris Charalampos , Sakellaropoulos Theodore , Lozano Aurelie , Kambadur Prabhanjan , Ntziachristos Panagiotis , Aifantis Iannis , Tsirigos Aristotelis 
Published: February 2018

AbstractThe metazoan genome is compartmentalized in areas of highly interacting chromatin known as topologically associating domains (TADs). TADs are demarcated by boundaries mostly conserved across cell types and even across species. However, a genome-wide characterization of TAD boundary strength in mammals is still lacking. In this study, we first use fused two-dimensional lasso as a machine learning method to improve Hi-C contact matrix reproducibility, and, subsequently, we categorize TAD boundaries based on their insulation score. We demonstrate that higher TAD boundary insulation scores are associated with elevated CTCF levels and that they may differ across cell types. Intriguingly, we observe that super-enhancers are preferentially insulated by strong boundaries. Furthermore, we demonstrate that strong TAD boundaries and super-enhancer elements are frequently co-duplicated in cancer patients. Taken together, our findings suggest that super-enhancers insulated by strong TAD boundaries may be exploited, as a functional unit, by cancer cells to promote oncogenesis.
A small molecule inhibitor of Rheb selectively targets mTORC1 signaling
Authors: Mahoney Sarah J. , Narayan Sridhar , Molz Lisa , Berstler Lauren A. , Kang Seong A. , Vlasuk George P. , Saiah Eddine 
Published: February 2018

AbstractThe small G-protein Rheb activates the mechanistic target of rapamycin complex 1 (mTORC1) in response to growth factor signals. mTORC1 is a master regulator of cellular growth and metabolism; aberrant mTORC1 signaling is associated with fibrotic, metabolic, and neurodegenerative diseases, cancers, and rare disorders. Point mutations in the Rheb switch II domain impair its ability to activate mTORC1. Here, we report the discovery of a small molecule (NR1) that binds Rheb in the switch II domain and selectively blocks mTORC1 signaling. NR1 potently inhibits mTORC1 driven phosphorylation of ribosomal protein S6 kinase beta-1 (S6K1) but does not inhibit phosphorylation of AKT or ERK. In contrast to rapamycin, NR1 does not cause inhibition of mTORC2 upon prolonged treatment. Furthermore, NR1 potently and selectively inhibits mTORC1 in mouse kidney and muscle in vivo. The data presented herein suggest that pharmacological inhibition of Rheb is an effective approach for selective inhibition of mTORC1 with therapeutic potential.
Silicon-Organic Hybrid (SOH) Mach-Zehnder Modulators for 100 Gbit/s on-off Keying
Authors: Wolf Stefan , Zwickel Heiner , Hartmann Wladislaw , Lauermann Matthias , Kutuvantavida Yasar , Kieninger Clemens , Altenhain Lars , Schmid Rolf , Luo Jingdong , Jen Alex K.-Y. , Randel Sebastian , Freude Wolfgang , Koos Christian 
Published: February 2018

AbstractElectro-optic modulators for high-speed on-off keying (OOK) are key components of short- and medium-reach interconnects in data-center networks. Small footprint, cost-efficient large-scale production, small drive voltages and ultra-low power consumption are of paramount importance for such devices. Here we demonstrate that the concept of silicon-organic hybrid (SOH) integration perfectly meets these challenges. The approach combines the unique processing advantages of large-scale silicon photonics with unrivalled electro-optic (EO) coefficients obtained by molecular engineering of organic materials. Our proof-of-concept experiments demonstrate generation and transmission of OOK signals at line rates of up to 100 Gbit/s using a 1.1 mm-long SOH Mach-Zehnder modulator (MZM) featuring a π-voltage of only 0.9 V. The experiment represents the first demonstration of 100 Gbit/s OOK on the silicon photonic platform, featuring the lowest drive voltage and energy consumption ever demonstrated for a semiconductor-based device at this data rate. We support our results by a theoretical analysis showing that the nonlinear transfer characteristic of the MZM can help to overcome bandwidth limitations of the modulator and the electric driver circuitry. We expect that high-speed, power-efficient SOH modulators may have transformative impact on short-reach networks, enabling compact transceivers with unprecedented efficiency, thus building the base of future interfaces with Tbit/s data rates.
Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer
Authors: Dhar Manjima , Wong Jessica , Che James , Matsumoto Melissa , Grogan Tristan , Elashoff David , Garon Edward B. , Goldman Jonathan W. , Sollier Christen Elodie , Di Carlo Dino , Kulkarni Rajan P. 
Published: February 2018

AbstractMetastatic non-small cell lung cancer (NSCLC) is a highly fatal and immunogenic malignancy. Although the immune system is known to recognize these tumor cells, one mechanism by which NSCLC can evade the immune system is via overexpression of programmed cell death ligand 1 (PD-L1). Recent clinical trials of PD-1 and PD-L1 inhibitors have returned promising clinical responses. Important for personalizing therapy, patients with higher intensity staining for PD-L1 on tumor biopsies responded better. Thus, there has been interest in using PD-L1 tumor expression as a criterion for patient selection. Currently available methods of screening involve invasive tumor biopsy, followed by histological grading of PD-L1 levels. Biopsies have a high risk of complications, and only allow sampling from limited tumor sections, which may not reflect overall tumor heterogeneity. Circulating tumor cell (CTC) PD-L1 levels could aid in screening patients, and could supplement tissue PD-L1 biopsy results by testing PD-L1 expression from disseminated tumor sites. Towards establishing CTCs as a screening tool, we developed a protocol to isolate CTCs at high purity and immunostain for PD-L1. Monitoring of PD-L1 expression on CTCs could be an additional biomarker for precision medicine that may help in determining response to immunotherapies.
Optical scheme for generating hyperentanglement having photonic qubit and time-bin via quantum dot and cross-Kerr nonlinearity
Authors: Hong Chang Ho , Heo Jino , Kang Min Sung , Jang Jingak , Yang Hyung Jin 
Published: February 2018

AbstractWe design an optical scheme to generate hyperentanglement correlated with degrees of freedom (DOFs) via quantum dots (QDs), weak cross-Kerr nonlinearities (XKNLs), and linearly optical apparatuses (including time-bin encoders). For generating hyperentanglement having its own correlations for two DOFs (polarization and time-bin) on two photons, we employ the effects of optical nonlinearities using a QD (photon-electron), a parity gate (XKNLs), and time-bin encodings (linear optics). In our scheme, the first nonlinear multi-qubit gate utilizes the interactions between photons and an electron of QD confined in a single-sided cavity, and the parity gate (second gate) uses weak XKNLs, quantum bus, and photon-number-resolving measurement to entangle the polarizations of two photons. Finally, for efficiency in generating hyperentanglement and for the experimental implementation of this scheme, we discuss how the QD-cavity system can be performed reliably, and also discuss analysis of the immunity of the parity gate (XKNLs) against the decoherence effect.
Support vector machines for explaining physiological stress response in Wood mice (Apodemus sylvaticus)
Authors: Sánchez-González Beatriz , Barja Isabel , Piñeiro Ana , Hernández-González M. Carmen , Silván Gema , Illera Juan Carlos , Latorre Roberto 
Published: February 2018

AbstractPhysiological stress response is a crucial adaptive mechanism for prey species survival. This paper aims to identify the main environmental and/or individual factors better explaining the stress response in Wood mice, Apodemus sylvaticus. We analyzed alterations in fecal glucocorticoid metabolite (FCM) concentration – extensively used as an accurate measure of the physiological stress response – of wild mice fecal samples seasonally collected during three years. Then, support vector machines were built to predict said concentration according to different stressors. These statistical tools appear to be particularly suitable for small datasets with substantial number of dimensions, corroborating that the stress response is an extremely complex process in which multiple factors can simultaneously partake in a context-dependent manner, i.e., the role of each potential stressor varies in time depending on other stressors. However, air-humidity, temperature and body-weight allowed us to explain the FCM fluctuation in 98% of our samples. The relevance of air-humidity and temperature altering FCM level could be linked to the presence of an abundant vegetation cover and, therefore, to food availability and predation risk perception. Body-weight might be related to the stress produced by reproduction and other intraspecific relationships such as social dominance or territorial behavior.
A novel gene of Kalanchoe daigremontiana confers plant drought resistance
Authors: Wang Li , Zhu Chen , Jin Lin , Xiao Aihua , Duan Jie , Ma Luyi 
Published: February 2018

AbstractKalanchoe (K.) daigremontiana is important for studying asexual reproduction under different environmental conditions. Here, we describe a novel KdNOVEL41 (KdN41) gene that may confer drought resistance and could thereby affect K. daigremontiana development. The detected subcellular localization of a KdN41/Yellow Fluorescent Protein (YFP) fusion protein was in the nucleus and cell membrane. Drought, salt, and heat stress treatment in tobacco plants containing the KdN41 gene promoter driving β-glucuronidase (GUS) gene transcription revealed that only drought stress triggered strong GUS staining in the vascular tissues. Overexpression (OE) of the KdN41 gene conferred improved drought resistance in tobacco plants compared to wild-type and transformed with empty vector plants by inducing higher antioxidant enzyme activities, decreasing cell membrane damage, increasing abscisic acid (ABA) content, causing reinforced drought resistance related gene expression profiles. The 3,3′-diaminobenzidine (DAB) and nitroblue tetrazolium (NBT) staining results also showed less relative oxygen species (ROS) content in KdN41-overexpressing tobacco leaf during drought stress. Surprisingly, by re-watering after drought stress, KdN41-overexpressing tobacco showed earlier flowering. Overall, the KdN41 gene plays roles in ROS scavenging and osmotic damage reduction to improve tobacco drought resistance, which may increase our understanding of the molecular network involved in developmental manipulation under drought stress in K. daigremontiana.
Compressive sensing for spatial and spectral flame diagnostics
Authors: Starling David J. , Ranalli Joseph 
Published: February 2018

AbstractCombustion research requires the use of state of the art diagnostic tools, including high energy lasers and gated, cooled CCDs. However, these tools may present a cost barrier for laboratories with limited resources. While the cost of high energy lasers and low-noise cameras continues to decline, new imaging technologies are being developed to address both cost and complexity. In this paper, we analyze the use of compressive sensing for flame diagnostics by reconstructing Raman images and calculating mole fractions as a function of radial depth for a highly strained, N2-H2 diffusion flame. We find good agreement with previous results, and discuss the benefits and drawbacks of this technique.
Surface ocean metabarcoding confirms limited diversity in planktonic foraminifera but reveals unknown hyper-abundant lineages
Authors: Morard Raphaël , Garet-Delmas Marie-José , Mahé Frédéric , Romac Sarah , Poulain Julie , Kucera Michal , de Vargas Colomban 
Published: February 2018

AbstractSince the advent of DNA metabarcoding surveys, the planktonic realm is considered a treasure trove of diversity, inhabited by a small number of abundant taxa, and a hugely diverse and taxonomically uncharacterized consortium of rare species. Here we assess if the apparent underestimation of plankton diversity applies universally. We target planktonic foraminifera, a group of protists whose known morphological diversity is limited, taxonomically resolved and linked to ribosomal DNA barcodes. We generated a pyrosequencing dataset of ~100,000 partial 18S rRNA foraminiferal sequences from 32 size fractioned photic-zone plankton samples collected at 8 stations in the Indian and Atlantic Oceans during the Tara Oceans expedition (2009–2012). We identified 69 genetic types belonging to 41 morphotaxa in our metabarcoding dataset. The diversity saturated at local and regional scale as well as in the three size fractions and the two depths sampled indicating that the diversity of foraminifera is modest and finite. The large majority of the newly discovered lineages occur in the small size fraction, neglected by classical taxonomy. These unknown lineages dominate the bulk [>0.8 µm] size fraction, implying that a considerable part of the planktonic foraminifera community biomass has its origin in unknown lineages.
Efficient non-cytotoxic fluorescent staining of halophiles
Authors: Maslov Ivan , Bogorodskiy Andrey , Mishin Alexey , Okhrimenko Ivan , Gushchin Ivan , Kalenov Sergei , Dencher Norbert A. , Fahlke Christoph , Büldt Georg , Gordeliy Valentin , Gensch Thomas , Borshchevskiy Valentin 
Published: February 2018

AbstractResearch on halophilic microorganisms is important due to their relation to fundamental questions of survival of living organisms in a hostile environment. Here we introduce a novel method to stain halophiles with MitoTracker fluorescent dyes in their growth medium. The method is based on membrane-potential sensitive dyes, which were originally used to label mitochondria in eukaryotic cells. We demonstrate that these fluorescent dyes provide high staining efficiency and are beneficial for multi-staining purposes due to the spectral range covered (from orange to deep red). In contrast with other fluorescent dyes used so far, MitoTracker does not affect growth rate, and remains in cells after several washing steps and several generations in cell culture. The suggested dyes were tested on three archaeal (Hbt. salinarum, Haloferax sp., Halorubrum sp.) and two bacterial (Salicola sp., Halomonas sp.) strains of halophilic microorganisms. The new staining approach provides new insights into biology of Hbt. salinarum. We demonstrated the interconversion of rod-shaped cells of Hbt. salinarium to spheroplasts and submicron-sized spheres, as well as the cytoplasmic integrity of giant rod Hbt. salinarum species. By expanding the variety of tools available for halophile detection, MitoTracker dyes overcome long-standing limitations in fluorescence microscopy studies of halophiles.
Mixing it up in the ocean carbon cycle and the removal of refractory dissolved organic carbon
Authors: Shen Yuan , Benner Ronald 
Published: February 2018

AbstractA large quantity of reduced carbon is sequestered in the ocean as refractory dissolved molecules that persist through several circuits of global overturning circulation. Key aspects of the cycling of refractory dissolved organic carbon (DOC) remain unknown, making it challenging to predict how this large carbon reservoir will respond to climate change. Herein we investigate mechanisms that remove refractory DOC using bioassay experiments with DOC isolated from surface, mesopelagic and deep waters of the Atlantic Ocean. The isolated DOC was refractory to degradation by native microbial communities, even at elevated concentrations. However, when the refractory DOC was introduced to a series of novel environmental conditions, including addition of a labile substrate, a microbial community from coastal waters and exposure to solar radiation, a substantial fraction (7–13%) was removed within 1.5 years. Our results suggest that while refractory molecules can persist in the ocean for millennia, removal is rapid when they encounter their fate. The observed and projected climate-induced slowdown of global overturning circulation could reduce the exposure of refractory molecules to disparate removal processes. Assuming a constant rate of production, the reservoir size of refractory DOC could increase as overturning circulation slows, providing a negative feedback to rising atmospheric CO2.
Prefrontal cortex modulates the correlations between brain-derived neurotrophic factor level, serotonin, and the autonomic nervous system
Authors: Chang Wei Hung , Lee I Hui , Chi Mei Hung , Lin Shih-Hsien , Chen Kao Chin , Chen Po See , Chiu Nan Tsing , Yao Wei Jen , Yang Yen Kuang 
Published: February 2018

AbstractTop-down regulation in the human brain and anatomical connections between the prefrontal cortex (PFC) and specific catecholamine-related regions have been well-studied. However, the way in which the PFC modulates downstream neuro-networks in terms of serotonin and the autonomic nervous system (ANS) by variation in the level of brain-derived neurotrophic factor (BDNF) is still unclear. We recruited sixty-seven healthy subjects. Serotonin transporter (SERT) availability was examined by SPECT with [123I]ADAM analysis; heart rate variability (HRV) testing was performed, and the BDNF level was measured. The Wisconsin card-sorting test (WCST), which assesses PFC activation, was also conducted. The interactions of BDNF level and SERT availability were significant in relation to the HRV indexes of low frequency, high frequency, total power, and mean heart rate range. Moderate to significant positive correlations between SERT availability and the above-mentioned HRV indexes existed only in subjects with a low BDNF level. Furthermore, in the low BDNF level group, only those with high WCST perseveration errors or low category completions exhibited significant positive correlations between SERT availability and HRV indexes. A lower BDNF level and poorer PFC function might modulate the synergistic effects of serotonergic and ANS systems in order to maintain brain physiological and psychological homeostasis.
Nuclear FAK and its kinase activity regulate VEGFR2 transcription in angiogenesis of adult mice
Authors: Sun Shaogang , Wu Hsin-Jung , Guan Jun-Lin 
Published: February 2018

AbstractFocal adhesion kinase (FAK) is essential in embryonic angiogenesis by regulating endothelial cell (EC) survival and barrier functions through its kinase-independent and –dependent activities. Here, we generated EC-specific tamoxifen-inducible FAK knockout and FAK kinase-defective (KD) mutant knockin mice to investigate the role of FAK and its kinase activity in angiogenesis of adult animals. Unlike previous observations of their differential defects in embryonic vascular development, both FAK ablation and inactivation of its kinase activity resulted in deficient angiogenesis in wound-healing as well as retinal angiogenesis models. Consistent with these phenotypes, loss of FAK or its kinase activity decreased EC proliferation and migration to similar extents, suggesting FAK primarily acts as a kinase for the regulation of adult EC-mediated angiogenesis. Further mechanistic analyses were carried out using an established mouse EC line MS1 cells. Interestingly, we found that FAK regulated the expression of VEGFR2, a central mediator of various EC functions and angiogenesis, which requires both FAK kinase activity and its translocation into the nucleus. Moreover, nuclear FAK was detected in the RNA polymerase II complex associated with VEGFR2 promoter, suggesting its direct participation in the transcriptional regulation of VEGFR2. Together, our results provide significant insights into the signaling mechanisms of FAK in angiogenesis that may contribute to future design of more effective angiogenesis related therapy.
Enhanced proton acceleration from an ultrathin target irradiated by laser pulses with plateau ASE
Authors: Wang Dahui , Shou Yinren , Wang Pengjie , Liu Jianbo , Li Chengcai , Gong Zheng , Hu Ronghao , Ma Wenjun , Yan Xueqing 
Published: February 2018

AbstractWe report a simulation study on proton acceleration driven by ultraintense laser pulses with normal contrast (107–109) containing nanosecond plateau amplified spontaneous emission (ASE). It’s found in hydrodynamic simulations that if the thickness of the targets lies in the range of hundreds nanometer matching the intensity and duration of ASE, the ablation pressure would push the whole target in the forward direction with speed exceeding the expansion velocity of plasma, resulting in a plasma density profile with a long extension at the target front and a sharp gradient at the target rear. When the main pulse irradiates the plasma, self-focusing happens at the target front, producing highly energetic electrons through direct laser acceleration(DLA) building the sheath field. The sharp plasma gradient at target rear ensures a strong sheath field. 2D particle-in-cell(PIC) simulations reveal that the proton energy can be enhanced by a factor of 2 compared to the case of using micrometer-thick targets.
IRE1α siRNA relieves endoplasmic reticulum stress-induced apoptosis and alleviates diabetic peripheral neuropathy in vivo and in vitro
Authors: Yao Weijie , Yang Xinwei , Zhu Jiayue , Gao Biane , Shi Haotian , Xu Liping 
Published: February 2018

AbstractDiabetic peripheral neuropathy (DPN) is mainly characterized by demyelination resulted from the apoptosis of the Schwann cell (SCs). Although the exact mechanisms underlying DPN remain unclear, endoplasmic reticulum (ER) stress is strongly implicated in the apoptosis. Under ER stress, activated inositol-requiring kinase 1α (IRE1α) unregulated CHOP, phosphorylated JNK and Caspase-12 to aggravate apoptosis-mediated damage of DPN. Therefore, we tested the hypothesis that inhibition of IRE1α could reduce the ER stress-related apoptosis to relieve DPN. Here, we show that IRE1α siRNA improved the neurological morphology and function of DPN rats and rescued ER stress-related apoptosis in the sciatic nerve. Additionally, RSC96 cells transfected with IRE1α siRNA were used as in vitro model of DPN. It was found that IRE1α siRNA also decreased high glucose-induced apoptosis and inhibited ER stress-related apoptosis in the cells. Altogether, our results suggest that IRE1α should be considered a potential therapeutic agent for DPN.
Pyrazines from bacteria and ants: convergent chemistry within an ecological niche
Authors: Silva-Junior Eduardo A. , Ruzzini Antonio C. , Paludo Camila R. , Nascimento Fabio S. , Currie Cameron R. , Clardy Jon , Pupo Mônica T. 
Published: February 2018

AbstractAnts use pheromones to coordinate their communal activity. Volatile pyrazines, for instance, mediate food resource gathering and alarm behaviors in different ant species. Here we report that leaf-cutter ant-associated bacteria produce a family of pyrazines that includes members previously identified as ant trail and alarm pheromones. We found that L-threonine induces the bacterial production of the trail pheromone pyrazines, which are common for the host leaf-cutter ants. Isotope feeding experiments revealed that L-threonine along with sodium acetate were the biosynthetic precursors of these natural products and a biosynthetic pathway was proposed.