bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do Chimeras Have Minds?
Authors: CAPPS BENJAMIN 
Published: September 2017

Abstract:Suppose that a colleague proposed a fantastic experiment: to introduce human stem cells into a neonatal mouse so that its entire brain developed into “human-like” neuronal structures. The colleague claimed it would still be a mouse, and that its chimeric brain would be nothing like a “human” one. It would not, as a result, have a moral status beyond its nonhuman animal origins. Thus, the “human neuron mouse” would allow scientists to tinker with human-like neurology in ways that would be precluded if it were a human being, and that would promise to lead to substantial understanding of the destructive and incurable brain diseases that befall humanity. The colleague does admit, however, that for reasons of comparative fidelity, experiments in human patients would be scientifically preferable, although in this case, neither ethically justified nor legally permitted. For that reason, it might be desirable to create a human brain in a nonhuman primate, where it would be more likely that significant human-like neuronal development would occur, but still could not become a person. This article explores the significance of a “human neuron chimpanzee,” and suggests that contradictions in the design of the experiment make it unethical to proceed in either murine or primate models.
Deep Brain Stimulation, Authenticity and Value
Authors: PUGH JONATHAN , MASLEN HANNAH , SAVULESCU JULIAN 
Published: September 2017

Abstract:Deep brain stimulation has been of considerable interest to bioethicists, in large part because of the effects that the intervention can occasionally have on central features of the recipient’s personality. These effects raise questions regarding the philosophical concept of authenticity. In this article, we expand on our earlier work on the concept of authenticity in the context of deep brain stimulation by developing a diachronic, value-based account of authenticity. Our account draws on both existentialist and essentialist approaches to authenticity, and Laura Waddell Ekstrom’s coherentist approach to personal autonomy. In developing our account, we respond to Sven Nyholm and Elizabeth O’Neill’s synchronic approach to authenticity, and explain how the diachronic approach we defend can have practical utility, contrary to Alexandre Erler and Tony Hope’s criticism of autonomy-based approaches to authenticity. Having drawn a distinction between the authenticity of an individual’s traits and the authenticity of that person’s values, we consider how our conception of authenticity applies to the context of anorexia nervosa in comparison to other prominent accounts of authenticity. We conclude with some reflections on the prudential value of authenticity, and by highlighting how the language of authenticity can be invoked to justify covert forms of paternalism that run contrary to the value of individuality that seems to be at the heart of authenticity.
High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma
Authors: Miller A , Asmann Y , Cattaneo L , Braggio E , Keats J , Auclair D , Lonial S ,   The MMRF CoMMpass Network, Russell S J , Stewart A K 
Published: September 2017

AbstractTumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients. In this population, the mean somatic and missense mutation loads were 405.84(s=608.55) and 63.90(s=95.88) mutations per patient, respectively. There was a positive linear relationship between mutation and neoantigen burdens (R2=0.862). The average predicted neoantigen load was 23.52(s=52.14) neoantigens with an average of 9.40(s=26.97) expressed neoantigens. Survival analysis revealed significantly shorter progression-free survival (PFS) in patients with greater than average somatic missense mutation load (N=163, 0.493 vs 0.726 2-year PFS, P=0.0023) and predicted expressed neoantigen load (N=214, 0.555 vs 0.729 2-year PFS, P=0.0028). This pattern is maintained when stratified by disease stage and cytogenetic abnormalities. Therefore, high mutation and neoantigen load are clinically relevant risk factors that negatively impact survival of MM patients under current standards of care.
High-throughput RNA structure probing reveals critical folding events during early 60S ribosome assembly in yeast
Authors: Burlacu Elena , Lackmann Fredrik , Aguilar Lisbeth-Carolina , Belikov Sergey , Nues Rob van , Trahan Christian , Hector Ralph D. , Dominelli-Whiteley Nicholas , Cockroft Scott L. , Wieslander Lars , Oeffinger Marlene , Granneman Sander 
Published: September 2017

AbstractWhile the protein composition of various yeast 60S ribosomal subunit assembly intermediates has been studied in detail, little is known about ribosomal RNA (rRNA) structural rearrangements that take place during early 60S assembly steps. Using a high-throughput RNA structure probing method, we provide nucleotide resolution insights into rRNA structural rearrangements during nucleolar 60S assembly. Our results suggest that many rRNA-folding steps, such as folding of 5.8S rRNA, occur at a very specific stage of assembly, and propose that downstream nuclear assembly events can only continue once 5.8S folding has been completed. Our maps of nucleotide flexibility enable making predictions about the establishment of protein–rRNA interactions, providing intriguing insights into the temporal order of protein–rRNA as well as long-range inter-domain rRNA interactions. These data argue that many distant domains in the rRNA can assemble simultaneously during early 60S assembly and underscore the enormous complexity of 60S synthesis.
Establishing and storing of deterministic quantum entanglement among three distant atomic ensembles
Authors: Yan Zhihui , Wu Liang , Jia Xiaojun , Liu Yanhong , Deng Ruijie , Li Shujing , Wang Hai , Xie Changde , Peng Kunchi 
Published: September 2017

AbstractIt is crucial for the physical realization of quantum information networks to first establish entanglement among multiple space-separated quantum memories and then, at a user-controlled moment, to transfer the stored entanglement to quantum channels for distribution and conveyance of information. Here we present an experimental demonstration on generation, storage, and transfer of deterministic quantum entanglement among three spatially separated atomic ensembles. The off-line prepared multipartite entanglement of optical modes is mapped into three distant atomic ensembles to establish entanglement of atomic spin waves via electromagnetically induced transparency light–matter interaction. Then the stored atomic entanglement is transferred into a tripartite quadrature entangled state of light, which is space-separated and can be dynamically allocated to three quantum channels for conveying quantum information. The existence of entanglement among three released optical modes verifies that the system has the capacity to preserve multipartite entanglement. The presented protocol can be directly extended to larger quantum networks with more nodes.
Springtime winds drive Ross Sea ice variability and change in the following autumn
Authors: Holland Marika M. , Landrum Laura , Raphael Marilyn , Stammerjohn Sharon 
Published: September 2017

AbstractAutumn sea ice trends in the western Ross Sea dominate increases in Antarctic sea ice and are outside the range simulated by climate models. Here we use a number of independent data sets to show that variability in western Ross Sea autumn ice conditions is largely driven by springtime zonal winds in the high latitude South Pacific, with a lead-time of 5 months. Enhanced zonal winds dynamically thin the ice, allowing an earlier melt out, enhanced solar absorption, and reduced ice cover the next autumn. This seasonal lag relationship has implications for sea ice prediction. Given a weakening trend in springtime zonal winds, this lagged relationship can also explain an important fraction of the observed sea ice increase. An analysis of climate models indicates that they simulate weaker relationships and wind trends than observed. This contributes to weak western Ross Sea ice trends in climate model simulations.
Large three-dimensional photonic crystals based on monocrystalline liquid crystal blue phases
Authors: Chen Chun-Wei , Hou Chien-Tsung , Li Cheng-Chang , Jau Hung-Chang , Wang Chun-Ta , Hong Ching-Lang , Guo Duan-Yi , Wang Cheng-Yu , Chiang Sheng-Ping , Bunning Timothy J. , Khoo Iam-Choon , Lin Tsung-Hsien 
Published: September 2017

AbstractAlthough there have been intense efforts to fabricate large three-dimensional photonic crystals in order to realize their full potential, the technologies developed so far are still beset with various material processing and cost issues. Conventional top-down fabrications are costly and time-consuming, whereas natural self-assembly and bottom-up fabrications often result in high defect density and limited dimensions. Here we report the fabrication of extraordinarily large monocrystalline photonic crystals by controlling the self-assembly processes which occur in unique phases of liquid crystals that exhibit three-dimensional photonic-crystalline properties called liquid-crystal blue phases. In particular, we have developed a gradient-temperature technique that enables three-dimensional photonic crystals to grow to lateral dimensions of ~1 cm (~30,000 of unit cells) and thickness of ~100 μm (~ 300 unit cells). These giant single crystals exhibit extraordinarily sharp photonic bandgaps with high reflectivity, long-range periodicity in all dimensions and well-defined lattice orientation.
IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease
Authors: Dambuza Ivy M. , He Chang , Choi Jin Kyeong , Yu Cheng-Rong , Wang Renxi , Mattapallil Mary J. , Wingfield Paul T. , Caspi Rachel R. , Egwuagu Charles E. 
Published: September 2017

AbstractInterleukin 35 (IL-35) is a heterodimeric cytokine composed of IL-12p35 and Ebi3 subunits. IL-35 suppresses autoimmune diseases while preventing host defense to infection and promoting tumor growth and metastasis by converting resting B and T cells into IL-10-producing and IL-35-producing regulatory B (Breg) and T (Treg) cells. Despite sharing the IL-12p35 subunit, IL-12 (IL-12p35/IL-12p40) promotes inflammatory responses whereas IL-35 (IL-12p35/Ebi3) induces regulatory responses, suggesting that IL-12p35 may have unknown intrinsic immune-regulatory functions regulated by its heterodimeric partner. Here we show that the IL-12p35 subunit has immunoregulatory functions hitherto attributed to IL-35. IL-12p35 suppresses lymphocyte proliferation, induces expansion of IL-10-expressing and IL-35-expressing B cells and ameliorates autoimmune uveitis in mice by antagonizing pathogenic Th17 responses. Recapitulation of essential immunosuppressive activities of IL-35 indicates that IL-12p35 may be utilized for in vivo expansion of Breg cells and autologous Breg cell immunotherapy. Furthermore, our uveitis data suggest that intrinsic immunoregulatory activities of other single chain IL-12 subunits might be exploited to treat other autoimmune diseases.
Continual reproduction of self-assembling oligotriazole peptide nanomaterials
Authors: Brea Roberto J. , Devaraj Neal K. 
Published: September 2017

AbstractAutocatalytic chemical reactions, whereby a molecule is able to catalyze its own formation from a set of precursors, mimic nature’s ability to generate identical copies of relevant biomolecules, and are thought to have been crucial for the origin of life. While several molecular autocatalysts have been previously reported, coupling autocatalytic behavior to macromolecular self-assembly has been challenging. Here, we report a non-enzymatic and chemoselective methodology capable of autocatalytically producing triskelion peptides that self-associate into spherical bioinspired nanostructures. Serial transfer experiments demonstrate that oligotriazole autocatalysis successfully leads to continual self-assembly of three-dimensional nanospheres. Triskelion-based spherical architectures offer an opportunity to organize biomolecules and chemical reactions in unique, nanoscale compartments. The use of peptide-based autocatalysts that are capable of self-assembly represents a promising method for the development of self-synthesizing biomaterials, and may shed light on understanding life’s chemical origins.
A coordination polymer for the site-specific integration of semiconducting sequences into DNA-based materials
Authors: Al-Mahamad Lamia L. G. , El-Zubir Osama , Smith David G. , Horrocks Benjamin R. , Houlton Andrew 
Published: September 2017

AbstractAdvances in bottom-up material design have been significantly progressed through DNA-based approaches. However, the routine integration of semiconducting properties, particularly long-range electrical conduction, into the basic topological motif of DNA remains challenging. Here, we demonstrate this with a coordination polymer derived from 6-thioguanosine (6-TG-H), a sulfur-containing analog of a natural nucleoside. The complexation reaction with Au(I) ions spontaneously assembles luminescent one-dimensional helical chains, characterized as {AuI(μ-6-TG)}n, extending many μm in length that are structurally analogous to natural DNA. Uniquely, for such a material, this gold-thiolate can be transformed into a wire-like conducting form by oxidative doping. We also show that this self-assembly reaction is compatible with a 6-TG-modified DNA duplex and provides a straightforward method by which to integrate semiconducting sequences, site-specifically, into the framework of DNA materials, transforming their properties in a fundamental and technologically useful manner.
Atomistic computer simulations of water interactions and dissolution of inorganic glasses
Authors: Du Jincheng , Rimsza Jessica M. 
Published: September 2017

AbstractComputer simulations at the atomistic scale play an increasing important role in understanding the structure features, and the structure–property relationships of glass and amorphous materials. In this paper, we reviewed atomistic simulation methods ranging from first principles calculations and ab initio molecular dynamics (AIMD) simulations, to classical molecular dynamics (MD), and meso-scale kinetic Monte Carlo (KMC) simulations and their applications to study the reactions and interactions of inorganic glasses with water and the dissolution behaviors of ﻿inorganic glasses. Particularly, the use of these simulation methods in understanding the reaction mechanisms of water with oxide glasses, water–glass interfaces, hydrated porous silica gels formation, the structure and properties of multicomponent glasses, and microstructure evolution are reviewed. The advantages and disadvantageous of these simulation methods are discussed and the current challenges and future direction of atomistic simulations in glass dissolution presented.
Onset of static and dynamic universality among molecular models of polymers
Authors: Takahashi Kazuaki Z. , Nishimura Ryuto , Yamato Nobuyoshi , Yasuoka Kenji , Masubuchi Yuichi 
Published: September 2017

AbstractA quantitatively accurate prediction of properties for entangled polymers is a long-standing challenge that must be addressed to enable efficient development of these materials. The complex nature of polymers is the fundamental origin of this challenge. Specifically, the chemistry, structure, and dynamics at the atomistic scale affect properties at the meso and macro scales. Therefore, quantitative predictions must start from atomistic molecular dynamics (AMD) simulations. Combined use of atomistic and coarse-grained (CG) models is a promising approach to estimate long-timescale behavior of entangled polymers. However, a systematic coarse-graining is still to be done for bridging the gap of length and time scales while retaining atomistic characteristics. Here we examine the gaps among models, using a generic mapping scheme based on power laws that are closely related to universality in polymer structure and dynamics. The scheme reveals the characteristic length and time for the onset of universality between the vastly different scales of an atomistic model of polyethylene and the bead-spring Kremer–Grest (KG) model. The mapping between CG model of polystyrene and the KG model demonstrates the fast onset of universality, and polymer dynamics up to the subsecond time scale are observed. Thus, quantitatively traceable timescales of polymer MD simulations can be significantly increased.
Endoplasmic reticulum stress preconditioning modifies intracellular mercury content by upregulating membrane transporters
Authors: Usuki Fusako , Fujimura Masatake , Yamashita Akio 
Published: September 2017

AbstractEndoplasmic reticulum (ER) stress preconditioning protects cells against methylmercury (MeHg) cytotoxicity by inducing integrated stress responses such as eIF2α phosphorylation, ATF4 accumulation, and nonsense-mediated mRNA decay (NMD) suppression. Here we demonstrated that ER stress preconditioning results in the upregulation of membrane transporters, leading to a decrease in intracellular mercury content. Our analyses showed that ER stress preconditioning upregulated the expression of methionine transporters that affect the cellular influx of MeHg, LAT1, LAT3, and SNAT2; and a membrane transporter that affects the efflux of MeHg, ABCC4, in MeHg-susceptible myogenic cells. Among these, ABCC4 transporter expression exhibited the greatest elevation. The functional significance of ABCC4 transporter in the efflux of MeHg was shown by the ABCC4 inhibition study. Additionally, we identified the role of phospho-eIF2α/ATF4 pathway in the upregulation of LAT1, SNAT2, and ABCC4 and the role of NMD suppression in LAT3 upregulation. Further, we detected that ER stress preconditioning amplified membrane transporter expression most likely through the translation of the upregulated mRNAs caused by ATF4-dependent transcription and NMD suppression. Taken together, these results suggested that the phospho-eIF2α/ATF4 pathway activation and NMD suppression may represent therapeutic targets for the alleviation of MeHg cytotoxicity by enhancing mercury efflux besides inducing protective stress responses.
Direct exciton emission from atomically thin transition metal dichalcogenide heterostructures near the lifetime limit
Authors: Wierzbowski Jakob , Klein Julian , Sigger Florian , Straubinger Christian , Kremser Malte , Taniguchi Takashi , Watanabe Kenji , Wurstbauer Ursula , Holleitner Alexander W. , Kaniber Michael , Müller Kai , Finley Jonathan J. 
Published: September 2017

AbstractWe demonstrate the reduction of the inhomogeneous linewidth of the free excitons in atomically thin transition metal dichalcogenides (TMDCs) MoSe2, WSe2 and MoS2 by encapsulation within few nanometre thick hBN. Encapsulation is shown to result in a significant reduction of the 10 K excitonic linewidths down to ∼3.5 meV for n-MoSe2, ∼5.0  meV for p-WSe2 and ∼4.8 meV for n-MoS2. Evidence is obtained that the hBN environment effectively lowers the Fermi level since the relative spectral weight shifts towards the neutral exciton emission in n-doped TMDCs and towards charged exciton emission in p-doped TMDCs. Moreover, we find that fully encapsulated MoS2 shows resolvable exciton and trion emission even after high power density excitation in contrast to non-encapsulated materials. Our findings suggest that encapsulation of mechanically exfoliated few-monolayer TMDCs within nanometre thick hBN dramatically enhances optical quality, producing ultra-narrow linewidths that approach the homogeneous limit.
Up-regulation of chemokine receptor CCR4 is associated with Human Hepatocellular Carcinoma malignant behavior
Authors: Cheng Xi , Wu Huo , Jin Zhi-Jian , Ma Ding , Yuen Stanley , Jing Xiao-Qian , Shi Min-Min , Shen Bai-Yong , Peng Cheng-Hong , Zhao Ren , Qiu Wei-Hua 
Published: September 2017

AbstractStudies indicate that the chemokine receptor is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, we initially demonstrated that CCR4 is overexpressed in HCC specimens, and its elevation in HCC tissues positively correlates with tumor capsule breakthrough and vascular invasion. Although overexpression of CCR4 failed to influent proliferation of HCC cells in vitro apparently, the prominent acceleration on HCC tumor growth in vivo was remarkable. The underlying mechanism may be involved in neovascularization. Interestingly, different from effect on proliferation, CCR4 overexpression could trigger HCC metastasis both in vitro and in vivo also induced HCC cell epithelial-mesenchymal transition (EMT) as well. Then we identified matrix metalloproteinase 2 (MMP2) as a direct target of CCR4 which plays an important role in CCR4-mediated HCC cell invasion, which was up-regulated by ERK/AKT signaling. Positive correlation between CCR4 and MMP2 expression was also observed in HCC tissues. In conclusion, our study suggested that chemokine receptor CCR4 promotes HCC malignancy and facilitated HCC cell metastases via ERK/AKT/MMP2 pathway. These findings suggest that CCR4 may be a potential new diagnostic and prognostic marker in HCC, and targeting CCR4 may be a potential therapeutic option for blocking HCC metastasis.
CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma
Authors: Hoe Susan Ling Ling , Tan Lu Ping , Abdul Aziz Norazlin , Liew Kitson , Teow Sin-Yeang , Abdul Razak Fazlyn Reeny , Chin Yoon Ming , Mohamed Shahrehan Nurul Ashikin , Chu Tai Lin , Mohd Kornain Noor Kaslina , Peh Suat-Cheng , Koay Cheng Eng , Lo Kwok-Wai , Ahmad Munirah , Ng Ching-Ching , Khoo Alan Soo-Beng 
Published: September 2017

AbstractSubpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.