bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barren plateaus in quantum neural network training landscapes
Authors: McClean Jarrod R. , Boixo Sergio , Smelyanskiy Vadim N. , Babbush Ryan , Neven Hartmut 
Published: November 2018

AbstractMany experimental proposals for noisy intermediate scale quantum devices involve training a parameterized quantum circuit with a classical optimization loop. Such hybrid quantum-classical algorithms are popular for applications in quantum simulation, optimization, and machine learning. Due to its simplicity and hardware efficiency, random circuits are often proposed as initial guesses for exploring the space of quantum states. We show that the exponential dimension of Hilbert space and the gradient estimation complexity make this choice unsuitable for hybrid quantum-classical algorithms run on more than a few qubits. Specifically, we show that for a wide class of reasonable parameterized quantum circuits, the probability that the gradient along any reasonable direction is non-zero to some fixed precision is exponentially small as a function of the number of qubits. We argue that this is related to the 2-design characteristic of random circuits, and that solutions to this problem must be studied.
Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility
Authors: Angulo-Urarte Ana , Casado Pedro , Castillo Sandra D. , Kobialka Piotr , Kotini Maria Paraskevi , Figueiredo Ana M. , Castel Pau , Rajeeve Vinothini , Milà-Guasch Maria , Millan Jaime , Wiesner Cora , Serra Helena , Muixi Laia , Casanovas Oriol , Viñals Francesc , Affolter Markus , Gerhardt Holger , Huveneers Stephan , Belting Heinz-Georg , Cutillas Pedro R. , Graupera Mariona 
Published: November 2018

AbstractAngiogenesis is a dynamic process relying on endothelial cell rearrangements within vascular tubes, yet the underlying mechanisms and functional relevance are poorly understood. Here we show that PI3Kα regulates endothelial cell rearrangements using a combination of a PI3Kα-selective inhibitor and endothelial-specific genetic deletion to abrogate PI3Kα activity during vessel development. Quantitative phosphoproteomics together with detailed cell biology analyses in vivo and in vitro reveal that PI3K signalling prevents NUAK1-dependent phosphorylation of the myosin phosphatase targeting-1 (MYPT1) protein, thereby allowing myosin light chain phosphatase (MLCP) activity and ultimately downregulating actomyosin contractility. Decreased PI3K activity enhances actomyosin contractility and impairs junctional remodelling and stabilization. This leads to overstretched endothelial cells that fail to anastomose properly and form aberrant superimposed layers within the vasculature. Our findings define the PI3K/NUAK1/MYPT1/MLCP axis as a critical pathway to regulate actomyosin contractility in endothelial cells, supporting vascular patterning and expansion through the control of cell rearrangement.
Water assisted biomimetic synergistic process and its application in water-jet rewritable paper
Authors: Xi Guan , Sheng Lan , Du Jiahui , Zhang Jinyan , Li Minjie , Wang Hongze , Ma Yufei , Zhang Sean Xiao-An 
Published: November 2018

AbstractThe colour of water-jet rewritable paper (WJRP) is difficult to be expanded via single hydrochromic molecule, especially black. Here, inspired by the amazing phenomenon of bound-water in cells enabling various biological transformations via facilitating synergistic inter-/intra-molecular proton transfer, we present a simple strategy toward WJRP based on binary systems containing less-sensitive acidochromic dyes and mild proton donors (or developers). With such a binary system containing commercial black dye as the colouring agent, benzyl 4-hydroxybenzoate as the developer, and biomimetic bound-water as proton-transferring medium, we successfully achieve the long-awaited black WJRP. Printed images on such WJRP have excellent performances and long retaining time (>1 month). In addition, the robustness, durability and reversibility of WJRP could be increased distinctly by using polyethylene terephthalate as substrate. This strategy significantly expands hydrochromic colours to entire visible range in an eco-friendly way, which opens an avenue of smart materials for practical needs and industrialization.
Warming assessment of the bottom-up Paris Agreement emissions pledges
Authors: Robiou du Pont Yann , Meinshausen Malte 
Published: November 2018

AbstractUnder the bottom-up architecture of the Paris Agreement, countries pledge Nationally Determined Contributions (NDCs). Current NDCs individually align, at best, with divergent concepts of equity and are collectively inconsistent with the Paris Agreement. We show that the global 2030-emissions of NDCs match the sum of each country adopting the least-stringent of five effort-sharing allocations of a well-below 2 °C-scenario. Extending such a self-interested bottom-up aggregation of equity might lead to a median 2100-warming of 2.3 °C. Tightening the warming goal of each country’s effort-sharing approach to aspirational levels of 1.1 °C and 1.3 °C could achieve the 1.5 °C and well-below 2 °C-thresholds, respectively. This new hybrid allocation reconciles the bottom-up nature of the Paris Agreement with its top-down warming thresholds and provides a temperature metric to assess NDCs. When taken as benchmark by other countries, the NDCs of India, the EU, the USA and China lead to 2.6 °C, 3.2 °C, 4 °C and over 5.1 °C warmings, respectively.
Coherent multidimensional spectroscopy of dilute gas-phase nanosystems
Authors: Bruder Lukas , Bangert Ulrich , Binz Marcel , Uhl Daniel , Vexiau Romain , Bouloufa-Maafa Nadia , Dulieu Olivier , Stienkemeier Frank 
Published: November 2018

AbstractTwo-dimensional electronic spectroscopy (2DES) is one of the most powerful spectroscopic techniques with unique sensitivity to couplings, coherence properties and real-time dynamics of a quantum system. While successfully applied to a variety of condensed phase samples, high precision experiments on isolated systems in the gas phase have been so far precluded by insufficient sensitivity. However, such experiments are essential for a precise understanding of fundamental mechanisms and to avoid misinterpretations. Here, we solve this issue by extending 2DES to isolated nanosystems in the gas phase prepared by helium nanodroplet isolation in a molecular beam-type experiment. This approach uniquely provides high flexibility in synthesizing tailored, quantum state-selected model systems of single and many-body character. In a model study of weakly-bound Rb2 and Rb3 molecules we demonstrate the method’s unique capacity to elucidate interactions and dynamics in tailored quantum systems, thereby also bridging the gap to experiments in ultracold quantum science.
Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression
Authors: Calcinotto Arianna , Brevi Arianna , Chesi Marta , Ferrarese Roberto , Garcia Perez Laura , Grioni Matteo , Kumar Shaji , Garbitt Victoria M. , Sharik Meaghen E. , Henderson Kimberly J. , Tonon Giovanni , Tomura Michio , Miwa Yoshihiro , Esplugues Enric , Flavell Richard A. , Huber Samuel , Canducci Filippo , Rajkumar Vincent S. , Bergsagel P. Leif , Bellone Matteo 
Published: November 2018

AbstractThe gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying thatPrevotella heparinolyticapromotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies.
Glucose metabolism induced by Bmp signaling is essential for murine skeletal development
Authors: Lee Seung-Yon , Abel E. Dale , Long Fanxin 
Published: November 2018

AbstractMuch of the mammalian skeleton originates from a cartilage template eventually replaced by bone via endochondral ossification. Despite much knowledge about growth factors and nuclear proteins in skeletal development, little is understood about the role of metabolic regulation. Here we report that genetic deletion of the glucose transporter Glut1 (Slc2a1), either before or after the onset of chondrogenesis in the limb, severely impairs chondrocyte proliferation and hypertrophy, resulting in dramatic shortening of the limbs. The cartilage defects are reminiscent to those caused by deficiency in Bmp signaling. Importantly, deletion of Bmpr1a in chondrocytes markedly reduces Glut1 levels in vivo, whereas recombinant BMP2 increases Glut1 mRNA and protein levels, boosting glucose metabolism in primary chondrocytes. Biochemical studies identify a Bmp-mTORC1-Hif1a signaling cascade resulting in upregulation of Glut1 in chondrocytes. The results therefore uncover a hitherto unknown connection between Bmp signaling and glucose metabolism in the regulation of cartilage development.
RET rearrangements are actionable alterations in breast cancer
Authors: Paratala Bhavna S. , Chung Jon H. , Williams Casey B. , Yilmazel Bahar , Petrosky Whitney , Williams Kirstin , Schrock Alexa B. , Gay Laurie M. , Lee Ellen , Dolfi Sonia C. , Pham Kien , Lin Stephanie , Yao Ming , Kulkarni Atul , DiClemente Frances , Liu Chen , Rodriguez-Rodriguez Lorna , Ganesan Shridar , Ross Jeffrey S. , Ali Siraj M. , Leyland-Jones Brian , Hirshfield Kim M. 
Published: November 2018

AbstractFusions involving the oncogenic gene RET have been observed in thyroid and lung cancers. Here we report RET gene alterations, including amplification, missense mutations, known fusions, novel fusions, and rearrangements in breast cancer. Their frequency, oncogenic potential, and actionability in breast cancer are described. Two out of eight RET fusions (NCOA4-RET and a novel RASGEF1A-RET fusion) and RET amplification were functionally characterized and shown to activate RET kinase and drive signaling through MAPK and PI3K pathways. These fusions and RET amplification can induce transformation of non-tumorigenic cells, support xenograft tumor formation, and render sensitivity to RET inhibition. An index case of metastatic breast cancer progressing on HER2-targeted therapy was found to have the NCOA4-RET fusion. Subsequent treatment with the RET inhibitor cabozantinib led to a rapid clinical and radiographic response. RET alterations, identified by genomic profiling, are promising therapeutic targets and are present in a subset of breast cancers.
Reward regulation in plant–frugivore networks requires only weak cues
Authors: Albrecht Jörg , Hagge Jonas , Schabo Dana G. , Schaefer H. Martin , Farwig Nina 
Published: November 2018

AbstractTheory assumes that fair trade among mutualists requires highly reliable communication. In plant–animal mutualisms the reliability of cues that indicate reward quality is often low. Therefore, it is controversial whether communication allows animal mutualists to regulate their reward intake. Here we show that even loose relationships between fruit brightness and nutritional rewards (r2 = 0.11–0.35) allow birds to regulate their nutrient intake across distinct European plant–frugivore networks. Resident, over-wintering generalist frugivores that interact with diverse plant species select bright, lipid-rich fruits, whereas migratory birds select dark, sugar- and antioxidant-rich fruits. Both nutritional strategies are consistent with previous physiological experiments suggesting that over-wintering generalists aim to maximize their energy intake, whereas migrants aim to enhance the build-up of body fat, their immune response and oxidative status during migration. Our results suggest that animal mutualists require only weak cues to regulate their reward intake according to specific nutritional strategies.
Dna2 processes behind the fork long ssDNA flaps generated by Pif1 and replication-dependent strand displacement
Authors: Rossi Silvia Emma , Foiani Marco , Giannattasio Michele 
Published: November 2018

AbstractDna2 is a DNA helicase-endonuclease mediating DSB resection and Okazaki fragment processing. Dna2 ablation is lethal and rescued by inactivation of Pif1, a helicase assisting Okazaki fragment maturation, Pol32, a DNA polymerase δ subunit, and Rad9, a DNA damage response (DDR) factor. Dna2 counteracts fork reversal and promotes fork restart. Here we show that Dna2 depletion generates lethal DNA structures activating the DDR. While PIF1 deletion rescues the lethality of Dna2 depletion, RAD9 ablation relieves the first cell cycle arrest causing genotoxicity after few cell divisions. Slow fork speed attenuates DDR in Dna2 deprived cells. Electron microscopy shows that Dna2-ablated cells accumulate long ssDNA flaps behind the forks through Pif1 and fork speed. We suggest that Dna2 offsets the strand displacement activity mediated by the lagging strand polymerase and Pif1, processing long ssDNA flaps to prevent DDR activation. We propose that this Dna2 function has been hijacked by Break Induced Replication in DSB processing.
NUAK2 is a critical YAP target in liver cancer
Authors: Yuan Wei-Chien , Pepe-Mooney Brian , Galli Giorgio G. , Dill Michael T. , Huang Hai-Tsang , Hao Mingfeng , Wang Yumeng , Liang Han , Calogero Raffaele A. , Camargo Fernando D. 
Published: November 2018

AbstractThe Hippo-YAP signaling pathway is a critical regulator of proliferation, apoptosis, and cell fate. The main downstream effector of this pathway, YAP, has been shown to be misregulated in human cancer and has emerged as an attractive target for therapeutics. A significant insufficiency in our understanding of the pathway is the identity of transcriptional targets of YAP that drive its potent growth phenotypes. Here, using liver cancer as a model, we identify NUAK2 as an essential mediator of YAP-driven hepatomegaly and tumorigenesis in vivo. By evaluating several human cancer cell lines we determine that NUAK2 is selectively required for YAP-driven growth. Mechanistically, we found that NUAK2 participates in a feedback loop to maximize YAP activity via promotion of actin polymerization and myosin activity. Additionally, pharmacological inactivation of NUAK2 suppresses YAP-dependent cancer cell proliferation and liver overgrowth. Importantly, our work here identifies a specific, potent, and actionable target for YAP-driven malignancies.
Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells
Authors: Al-Hrout Ala’a , Chaiboonchoe Amphun , Khraiwesh Basel , Murali Chandraprabha , Baig Badriya , El-Awady Raafat , Tarazi Hamadeh , Alzahmi Amnah , Nelson David R. , Greish Yaser E. , Ramadan Wafaa , Salehi-Ashtiani Kourosh , Amin Amr 
Published: November 2018

AbstractPoor prognoses remain the most challenging aspect of hepatocellular carcinoma (HCC) therapy. Consequently, alternative therapeutics are essential to control HCC. This study investigated the anticancer effects of safranal against HCC using in vitro, in silico, and network analyses. Cell cycle and immunoblot analyses of key regulators of cell cycle, DNA damage repair and apoptosis demonstrated unique safranal-mediated cell cycle arrest at G2/M phase at 6 and 12 h, and at S-phase at 24 h, and a pronounced effect on DNA damage machinery. Safranal also showed pro-apoptotic effect through activation of both intrinsic and extrinsic initiator caspases; indicating ER stress-mediated apoptosis. Gene set enrichment analysis provided consistent findings where UPR is among the top terms of up-regulated genes in response to safranal treatment. Thus, proteins involved in ER stress were regulated through safranal treatment to induce UPR in HepG2 cells.
Construction and characterization of a Saccharomyces cerevisiae strain able to grow on glucosamine as sole carbon and nitrogen source
Authors: Flores Carmen-Lisset , Gancedo Carlos 
Published: November 2018

AbstractSaccharomyces cerevisiae can transport and phosphorylate glucosamine, but cannot grow on this amino sugar. While an enzyme catalyzing the reaction from glucosamine-6-phosphate to fructose-6-phosphate, necessary for glucosamine catabolism, is present in yeasts using N-acetylglucosamine as carbon source, a sequence homology search suggested that such an enzyme is absent from Saccharomyces cerevisiae. The gene YlNAG1 encoding glucosamine-6-phosphate deaminase from Yarrowia lipolytica was introduced into S. cerevisiae and growth in glucosamine tested. The constructed strain grew in glucosamine as only carbon and nitrogen source. Growth on the amino sugar required respiration and caused an important ammonium excretion. Strains overexpressing YlNAG1 and one of the S. cerevisiae glucose transporters HXT1, 2, 3, 4, 6 or 7 grew in glucosamine. The amino sugar caused catabolite repression of different enzymes to a lower extent than that produced by glucose. The availability of a strain of S. cerevisiae able to grow on glucosamine opens new possibilities to investigate or manipulate pathways related with glucosamine metabolism in a well-studied organism.
Simultaneous Blood Flow Measurement and Dermoscopy of Skin Lesions Using Dual-Mode Dermascope
Authors: White Sean M. , Valdebran Manuel , Kelly Kristen M. , Choi Bernard 
Published: November 2018

AbstractDermascopes are commonly utilized for the qualitative visual inspection of skin lesions. While automated image processing techniques and varied illumination strategies have been used to aid in structural analysis of lesions, robust quantification of functional information is largely unknown. To address this knowledge gap, we have developed a compact, handheld dermascope that enables real-time blood flow measurements of skin during conventional visual inspection. In-vitro characterization demonstrated that the dermascope is capable of quantifying changes in flow across a physiologically relevant range even when used in a handheld manner with clinic lighting and dermascope LEDs on. In a small pilot clinical study, we demonstrated the dermascope’s ability to detect flow differences between two distinct lesion types.
Unique, Intersecting, and Overlapping Roles of C/EBP β and CREB in Cells of the Innate Immune System
Authors: Larabee Jason L. , Hauck Garrett , Ballard Jimmy D. 
Published: November 2018

AbstractCREB and C/EBP β signaling pathways are modulated during inflammation and also targeted by Bacillus anthracis edema toxin (ET), but how these factors individually and jointly contribute to changes in immune cell function is poorly understood. Using CRISPR/Cas9 gene editing, macrophage cell lines lacking CREB and isoforms of C/EBP β were generated and analyzed for changes in responses to LPS, ET, and IL-4. Macrophages lacking C/EBP β suppressed induction of IL-10 and Arg1, while IL-6 was increased in these cells following exposure to LPS. Examination of C/EBP β isoforms indicated the 38 kDa isoform was necessary for the expression of IL-10 and Arg1. ChIP-Seq analysis of CREB and C/EBP β binding to targets on the chromosome of human PBMC identified several regions where both factors overlapped in their binding, suggesting similar gene targeting or cooperative effects. Based on the ChIP-Seq data, a panel of previously unknown targets of CREB and C/EBP β was identified and includes genes such as VNN2, GINS4, CTNNBL1, and SULF2. Isoforms of a transcriptional corepressor, transducin-like enhancer of Split (TLE), were also found to have CREB and C/EBP β binding their promoter and were up regulated by ET. Finally, we explore a possible layer of C/EBP β regulation by a protein complex consisting of adenomatous polyposis coli (APC) and PKA. Collectively, these data provide new insights into the role of CREB and C/EBP β as immunosignaling regulators and targets of an important bacterial virulence factor.
Low-level light therapy reduces platelet destruction during extracorporeal circulation
Authors: Drohomirecka Anna , Iwaszko Alicja , Walski Tomasz , Pliszczak-Król Aleksandra , Wąż Grzegorz , Graczyk Stanisław , Gałecka Katarzyna , Czerski Albert , Bujok Jolanta , Komorowska Małgorzata 
Published: November 2018

AbstractExtracorporeal circulation causes many deleterious effects on blood cells. Low-level light therapy (LLLT) in the red/near-infrared spectral range is known for its cytoprotective properties but its use during cardiopulmonary bypass (CPB) has not yet been studied. We aimed to assess whether LLLT protects platelets during CPB. 24 pigs were connected to 1-hour-CPB and observed for the next 23 hours. In 12 animals, blood circulating through the oxygenator was treated with LLLT. Platelet count and function were monitored throughout the experiment. The decrease in platelet count was greater in the control group, especially during CPB and after 24 hours. In LLLT group CD62P expression remained quite stable up to the 12th hour of the experiment, whereas in the control group it continuously decreased till the end of observation. Platelets in the control group were more prone to aggregation in the postoperative period than at the beginning of the experiment, whereas platelets in the LLLT group aggregated similarly or less intense. Limitation of platelet loss, pattern of aggregation and CD62P expression suggest that LLLT may stabilize platelet function during CPB and diminish the negative effects associated with the interaction of cells with an artificial surface.
Mechanistic Interaction Study of Bromo-Noscapine with Bovine Serum Albumin employing Spectroscopic and Chemoinformatics Approaches
Authors: Sood Damini , Kumar Neeraj , Rathee Garima , Singh Anju , Tomar Vartika , Chandra Ramesh 
Published: November 2018

AbstractBromo-Noscapine (BrNs) is a tubulin-binding cytotoxic agent with significant activity against breast and lung cancer. The mechanistic interaction insight into the binding of bovine serum albumin (BSA) with BrNs can provide critical information about the pharmacodynamics and pharmacokinetics properties. Here, various spectroscopic techniques and computational methods were employed to understand the dynamics of BrNs and BSA interaction. The intrinsic fluorescence of BSA was quenched by BrNs through a static quenching procedure. The stoichiometry of BrNs-BSA complex was 1:1 and binding constant of the complex was in the order of 103 M−1at 298 K. Based on thermodynamic analysis, it was deduced that binding process of the BrNs with BSA was spontaneous and exothermic, and the major forces between BrNs and BSA were van der waals forces and hydrogen bonding. Moreover, results of FT-IR, CD, UV spectra concluded significant conformational change in BSA on binding with BrNs. Thein vitrofindings were further confirmed byin silicoassays. Molecular docking showed strong interactions with score of −8.08 kcal/mol. Molecular dynamics simulation analysis also suggested the stable binding with lower deviation in RMSD and RMSF values through persistent long simulation run. This study suggests optimal efficiency of diffusion of the BrNs into the bloodstream for the treatment of cancer.