bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling Neodymium Isotopes in the Ocean Component of the Community Earth System Model (CESM1)
Authors: Gu Sifan , Liu Zhengyu , Jahn Alexandra , Rempfer Johannes , Zhang Jiaxu , Joos Fortunat 
Published: February 2019

AbstractNeodymium (Nd) isotopic composition (εNd) is an important tracer for water mass mixing and the reconstruction of past ocean circulation. To allow for a direct model‐data comparison, we have implemented Nd isotopes in the ocean component of the Community Earth System Model (CESM1.3). The model is able to capture the major features of the observed modern distribution of both εNd and Nd concentrations. Our model provides a useful tool for the interpretation of εNd reconstructions. For example, we show that in an idealized North Atlantic freshwater hosing experiment, εNd changes in the Atlantic are documenting primarily the changes in water mass mixing and are hardly affected by the concomitant and large changes in the marine biological productivity and organic matter fluxes. However, the hosing experiment also shows that the end‐member changes due to the change of ocean circulation can influence the interpretation of εNd in the Atlantic, depending on the location. The implementation of Nd, together with other existing tracers, such as δ18O, 231Pa/230Th, δ13C, and radiocarbon in the same model, can improve our understanding of past ocean circulation significantly.
lncRNA ZEB1-AS1 promotes pulmonary fibrosis through ZEB1-mediated epithelial–mesenchymal transition by competitively binding miR-141-3p
Authors: Qian Weibin , Cai Xinrui , Qian Qiuhai , Peng Wei , Yu Jie , Zhang Xinying , Tian Li , Wang Can 
Published: February 2019

AbstractLong non-coding RNAs (lncRNAs) have been reported to be involved in various pathophysiological processes in many diseases. However, the role and mechanism of lncRNAs in pulmonary fibrosis have not been explicitly delineated. In the present study, we found that lncRNA ZEB1 antisense RNA 1 (ZEB1-AS1) is upregulated in the lungs of BLM-induced rats and TGF-β1-induced RLE-6TN cells, and positively correlated with the levels of ZEB1, an epithelial–mesenchymal transition (EMT) master regulator. Knockdown of ZEB1-AS1 alleviated BLM-induced fibrogenesis, in vivo, via inhibiting EMT progress. Mechanistically, we identified that ZEB1-AS1 promoted fibrogenesis in RLE-6TN cells and ZEB1-AS1 silencing inhibited TGF-β1-induced fibrogenesis through modulation of miR-141-3p. Further experiments revealed that ZEB1-AS1 acted as competing endogenous RNA (ceRNA) of miR-141-3p: forced expression of ZEB1-AS1 reduced the expression of miR-141-3p to activate Zinc-finger Ebox Binding Homeobox 1 (ZEB1) in RLE-6TN cells. In addition, we found that upregulation of miR-141-3p prevented fibrogenesis by targeting ZEB1. Therefore, our finding suggested lncRNA ZEB1-AS1 as a new profibrotic molecule that acts as a regulator of miR-141-3p/ZEB1 axis during lung fibrosis and demonstrated ZEB1-AS1 as a potential therapeutic target for the prevention and treatment of pulmonary fibrosis.
DJ-1 modulates the unfolded protein response and cell death via upregulation of ATF4 following ER stress
Authors: Yang Jungwoo , Kim Kwang Soo , Iyirhiaro Grace O. , Marcogliese Paul C. , Callaghan Steve M. , Qu Dianbo , Kim Woo Jae , Slack Ruth S. , Park David S. 
Published: February 2019

AbstractThe unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is a feature of many neurodegenerative diseases including Alzheimer’s disease, Huntington’s disease and Parkinson’s disease (PD). Although the vast majority of PD is sporadic, mutations in a number of genes including PARK7 which encodes the protein DJ-1 have been linked to early-onset, familial PD. In this regard, both PD of sporadic and genetic origins exhibit markers of ER stress-induced UPR. However, the relationship between pathogenic mutations in PARK7 and ER stress-induced UPR in PD pathogenesis remains unclear. In most contexts, DJ-1 has been shown to protect against neuronal injury. However, we find that DJ-1 deficiency ameliorates death in the context of acute ER stress in vitro and in vivo. DJ-1 loss decreases protein and transcript levels of ATF4, a transcription factor critical to the ER response and reduces the levels of CHOP and BiP, its downstream effectors. The converse is observed with DJ-1 over-expression. Importantly, we find that over-expression of wild-type and PD-associated mutant form of PARK7L166P, enhances ER stress-induced neuronal death by regulating ATF4 transcription and translation. Our results demonstrate a previously unreported role for wild-type and mutant DJ-1 in the regulation of UPR and provides a potential link to PD pathogenesis.
Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy
Authors: Friedman Jennifer , Smith Desiree E. , Issa Mahmoud Y. , Stanley Valentina , Wang Rengang , Mendes Marisa I. , Wright Meredith S. , Wigby Kristen , Hildreth Amber , Crawford John R. , Koehler Alanna E. , Chowdhury Shimul , Nahas Shareef , Zhai Liting , Xu Zhiwen , Lo Wing-Sze , James Kiely N. , Musaev Damir , Accogli Andrea , Guerrero Kether , Tran Luan T. , Omar Tarek E. I. , Ben-Omran Tawfeg , Dimmock David , Kingsmore Stephen F. , Salomons Gajja S. , Zaki Maha S. , Bernard Geneviève , Gleeson Joseph G. 
Published: February 2019

AbstractAminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes.
Biallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish
Authors: Siekierska Aleksandra , Stamberger Hannah , Deconinck Tine , Oprescu Stephanie N. , Partoens Michèle , Zhang Yifan , Sourbron Jo , Adriaenssens Elias , Mullen Patrick , Wiencek Patrick , Hardies Katia , Lee Jeong-Soo , Giong Hoi-Khoanh , Distelmaier Felix , Elpeleg Orly , Helbig Katherine L. , Hersh Joseph , Isikay Sedat , Jordan Elizabeth , Karaca Ender , Kecskes Angela , Lupski James R. , Kovacs-Nagy Reka , May Patrick , Narayanan Vinodh , Pendziwiat Manuela , Ramsey Keri , Rangasamy Sampathkumar , Shinde Deepali N. , Spiegel Ronen , Timmerman Vincent , von Spiczak Sarah , Helbig Ingo ,   C4RCD Research Group, Balak Chris , Belnap Newell , Claasen Ana , Courtright Amanda , de Both Matt , Huentelman Matthew J. , Naymik Marcus , Richholt Ryan , Siniard Ashley L. , Szelinger Szabolcs , Craig David W. , Schrauwen Isabelle ,   AR working group of the EuroEPINOMICS RES Consortium, Afawi Zaid , Balling Rudi , Baulac Stéphanie , Barišić Nina , Caglayan Hande S. , Craiu Dana , Guerrero-López Rosa , Guerrini Renzo , Hjalgrim Helle , Jähn Johanna , Klein Karl Martin , Leguern Eric , Lemke Johannes R. , Lerche Holger , Marini Carla , Møller Rikke S. , Muhle Hiltrud , Rosenow Felix , Serratosa Jose , Suls Arvid , Stephani Ulrich , Štěrbová Katalin , Striano Pasquale , Zara Federico , Weckhuysen Sarah , Francklyn Christopher , Antonellis Anthony , de Witte Peter , De Jonghe Peter 
Published: February 2019

AbstractAminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations in ARSs have emerged as a cause of recessive, often complex neurological disease traits. Here we report an allelic series consisting of seven novel and two previously reported biallelic variants in valyl-tRNA synthetase (VARS) in ten patients with a developmental encephalopathy with microcephaly, often associated with early-onset epilepsy. In silico, in vitro, and yeast complementation assays demonstrate that the underlying pathomechanism of these mutations is most likely a loss of protein function. Zebrafish modeling accurately recapitulated some of the key neurological disease traits. These results provide both genetic and biological insights into neurodevelopmental disease and pave the way for further in-depth research on ARS related recessive disorders and precision therapies.
Ferromagnetism above 1000 K in a highly cation-ordered double-perovskite insulator Sr3OsO6
Authors: Wakabayashi Yuki K. , Krockenberger Yoshiharu , Tsujimoto Naoto , Boykin Tommy , Tsuneyuki Shinji , Taniyasu Yoshitaka , Yamamoto Hideki 
Published: February 2019

AbstractMagnetic insulators have wide-ranging applications, including microwave devices, permanent magnets and future spintronic devices. However, the record Curie temperature (TC), which determines the temperature range in which any ferri/ferromagnetic system remains stable, has stood still for over eight decades. Here we report that a highly B-site ordered cubic double-perovskite insulator, Sr3OsO6, has the highest TC (of ~1060 K) among all insulators and oxides; also, this is the highest magnetic ordering temperature in any compound without 3d transition elements. The cubic B-site ordering is confirmed by atomic-resolution scanning transmission electron microscopy. The electronic structure calculations elucidate a ferromagnetic insulating state with Jeff = 3/2 driven by the large spin-orbit coupling of Os6+ 5d2 orbitals. Moreover, the Sr3OsO6 films are epitaxially grown on SrTiO3 substrates, suggesting that they are compatible with device fabrication processes and thus promising for spintronic applications.
Pathogenic function of bystander-activated memory-like CD4+ T cells in autoimmune encephalomyelitis
Authors: Lee Hong-Gyun , Lee Jae-Ung , Kim Do-Hyun , Lim Sangho , Kang Insoo , Choi Je-Min 
Published: February 2019

AbstractT cells generate antigen-specific immune responses to their cognate antigen as a hallmark of adaptive immunity. Despite the importance of antigen-specific T cells, here we show that antigen non-related, bystander memory-like CD4+ T cells also significantly contribute to autoimmune pathogenesis. Transcriptome analysis demonstrates that interleukin (IL)-1β- and IL-23-prime T cells that express pathogenic TΗ17 signature genes such as RORγt, CCR6, and granulocyte macrophage colony-stimulating factor (GM-CSF). Importantly, when co-transferred with myelin-specific 2D2 TCR-transgenic naive T cells, unrelated OT-II TCR-transgenic memory-like TH17 cells infiltrate the spinal cord and produce IL-17A, interferon (IFN)-γ, and GM-CSF, increasing the susceptibility of the recipients to experimental autoimmune encephalomyelitis in an IL-1 receptor-dependent manner. In humans, IL-1R1high memory CD4+ T cells are major producers of IL-17A and IFN-γ in response to IL-1β and IL-23. Collectively, our findings reveal the innate-like pathogenic function of antigen non-related memory CD4+ T cells, which contributes to the development of autoimmune diseases.
Designing chemical analogs to PbTe with intrinsic high band degeneracy and low lattice thermal conductivity
Authors: He Jiangang , Xia Yi , Naghavi S. Shahab , Ozoliņš Vidvuds , Wolverton Chris 
Published: February 2019

AbstractHigh-efficiency thermoelectric materials require simultaneously high power factors and low thermal conductivities. Aligning band extrema to achieve high band degeneracy, as realized in PbTe, is one of the most efficient approaches to enhance power factor. However, this approach usually relies on band structure engineering, e.g., via chemical doping or strain. By employing first-principles methods with explicit computation of phonon and carrier lifetimes, here we show two full-Heusler compounds Li2TlBi and Li2InBi have exceptionally high power factors and low lattice thermal conductivities at room temperature. The expanded rock-salt sublattice of these compounds shifts the valence band maximum to the middle of the Σ line, increasing the band degeneracy by a factor of three. Meanwhile, resonant bonding in the PbTe-like sublattice and soft Tl–Bi (In–Bi) bonding interaction is responsible for intrinsic low lattice thermal conductivities. Our results present an alternative strategy of designing high performance thermoelectric materials.
Significance of baseline neutrophil-to-lymphocyte ratio for progression-free survival of patients with HER2-positive breast cancer treated with trastuzumab emtansine
Authors: Imamura Michiko , Morimoto Takashi , Egawa Chiyomi , Fukui Reiko , Bun Ayako , Ozawa Hiromi , Miyagawa Yoshimasa , Fujimoto Yukie , Higuchi Tomoko , Miyoshi Yasuo 
Published: February 2019

AbstractThe efficacy of trastuzumab emtansine (T-DM1) is prolonged for some patients; however, the predictive factors remain unknown. We focused on a peripheral blood biomarker, the neutrophil-to-lymphocyte ratio (NLR), regarding T-DM1 treatment efficacy. Fifty-three advanced or metastatic breast cancers treated with T-DM1 were retrospectively recruited from three institutes. The NLR in the peripheral blood was measured at baseline and after one cycle. The cutoff value of the NLR was set at median value 2.56. The progression-free survival (PFS) of patients with NLR-low at baseline (n = 26; median, not reached) was significantly better than that of patients with NLR-high (n = 27; median, 4.13 months; hazard ratio [HR], 0.226; 95% confidence interval [CI], 0.112–0.493; p = 0.0001). Longer overall survival was significantly associated with a low NLR (HR, 0.384; 95% CI, 0.170–0.910; p = 0.0296). In the subgroup analysis, patients with NLR-low consistently had longer PFS compared to those with NLR-high irrespective of the number of prior chemotherapy regimens, prior trastuzumab, visceral metastasis, estrogen receptor status, and human epidermal growth factor receptor 2 (HER2) score. Although detailed mechanisms remain unknown, treatment efficacy of T-DM1 may be partly mediated by activation of the immune system. Low baseline NLR appears to be beneficial for treatment with T-DM1 in HER2-positive breast cancers.
Materials Selection and Mechanism of Non-linear Conduction in Chalcogenide Selector Devices
Authors: Li Huanglong , Robertson John 
Published: February 2019

AbstractThe electronic structure and conduction mechanism of chalcogenide-based Ovonic threshold switches (OTS) used as selectors in cross-point memory arrays is derived from density functional calculations and quasi-Fermi level models. The switching mechanism in OTS is primarily electronic. This uses a specific electronic structure, with a wide tail of localized states below the conduction band edge. In amorphous GeSe2−x the conduction band consists of Ge-Se σ*states with a low effective mass, and with a broad tail of localized Ge-Ge σ* states below this band edge. This leads to the OTS behavior. At high fields the electron quasi-EF moves up through these tail states, lowering the conductivity activation energy, and giving the non-linear switching process. The 4:2 coordinated GeSe2−x based alloys are the most favorable OTS material because they have the correct network connectivity to give a high electron mobility and lack of crystallization, a favorable band structure to produce the non-linear conduction, an optimum band gap, and with nitrogen or carbon alloying, a sufficiently low off-current.
Evaluation of vascular pain in patients with colorectal cancer receiving peripheral venous chemotherapy with or without oxaliplatin
Authors: Matsuoka Taisuke , Yoshida Yoichiro , Aisu Naoya , Yamada Teppei , Mogi Ai , Komono Akira , Sakamoto Ryohei , Kojima Daibo , Yoshimatsu Gumpei , Kiyomi Fumiaki , Kodama Shohta , Hasegawa Suguru 
Published: February 2019

AbstractOxaliplatin is a key chemotherapy drug in patients with colorectal cancer. Administration of oxaliplatin via a peripheral vein often causes vascular pain. However, no studies have evaluated vascular pain in patients with colorectal cancer in relation to peripheral venous administration of chemotherapy with or without oxaliplatin. We evaluated oxaliplatin-induced vascular pain using subjective and objective methods. We determined if oxaliplatin induced vascular pain in patients with colorectal cancer using a Visual Analog Scale (VAS) and a PainVision PS-2100 device. We compared VAS score between chemotherapy regimens with or without oxaliplatin, and between genders. We also examined the correlations of VAS score with pain intensity examined by the PainVision PS-2100, and with age and vessel diameter. A total of 98 patients with colorectal cancer were enrolled in this study, including 78 patients who received oxaliplatin via peripheral venous administration and 20 who received chemotherapy without oxaliplatin. The median VAS scores in patients with and without oxaliplatin were 36.5 (interquartile range 9.0–60.0) and 0 (0–4.0), respectively (P < 0.001), and the median pain intensities according to PainVision were 43.5 (14.3–98) and 36.5 (9.3–58.5), respectively (P < 0.001). There was a positive correlation between VAS and pain intensity (r = 0.584), but no correlation between VAS score and age (r = −0.174) or vessel diameter (r = −0.107). Peripheral venous administration of oxaliplatin induced vascular pain, measured both subjectively and objectively, in patients with colorectal cancer, regardless of vessel diameter.
Endocan as a marker of microvascular inflammation in kidney transplant recipients
Authors: Lee Yu Ho , Kim Se-Yun , Moon Haena , Seo Jung-Woo , Kim Dong-Jin , Park Seon Hwa , Kim Yang-Gyun , Moon Ju-Young , Kim Jin Sug , Jeong Kyung-Hwan , Lim Sung-Jig , Kim Chan-Duck , Park Jae Berm , Chung Byung Ha , Kim Yeong Hoon , Yang Jaeseok , Yang Hyung-In , Kim Kyoung Soo , Lee Sang-Ho 
Published: February 2019

AbstractEndocan is a water-soluble proteoglycan exclusively secreted by vascular endothelium. Endocan levels may be elevated in kidney transplant recipients experiencing antibody-mediated rejection (ABMR), which is characterized by vascular inflammation in transplanted kidney. We evaluated the clinical relevance of endocan as markers of microvascular inflammation in patients who underwent kidney transplantation. Plasma and urinary endocan levels were measured in 203 kidney transplant recipients and were compared across different etiologies of allograft dysfunction and various pathologic scores. Both plasma and urinary endocan levels were significantly higher in patients with acute ABMR than those in patients with normal pathology, acute tubular necrosis (ATN), acute pyelonephritis, BK virus associated nephropathy (BKVN), and T-cell mediated rejection (TCMR). Patients with chronic active ABMR also exhibited significantly higher plasma and urinary endocan levels than patients with long-term graft survival. Scores of glomerulitis and peritubular capillaritis, which are typical features of microvascular inflammation, were significantly elevated in patients with higher plasma and/or urinary endocan levels. Furthermore, plasma and urinary endocan levels could effectively discriminate ABMR from ATN, BKVN, and TCMR. Finally, patients exhibiting high urinary and plasma endocan levels in acute ABMR group showed significantly worse renal survival. Altogether, plasma and urinary endocan levels may serve as potential markers of microvascular inflammation in kidney transplant recipients.
A subtelomeric region affects telomerase-negative replicative senescence in Saccharomyces cerevisiae
Authors: Jolivet Pascale , Serhal Kamar , Graf Marco , Eberhard Stephan , Xu Zhou , Luke Brian , Teixeira Maria Teresa 
Published: February 2019

AbstractIn eukaryotes, telomeres determine cell proliferation potential by triggering replicative senescence in the absence of telomerase. In Saccharomyces cerevisiae, senescence is mainly dictated by the first telomere that reaches a critically short length, activating a DNA-damage-like response. How the corresponding signaling is modulated by the telomeric structure and context is largely unknown. Here we investigated how subtelomeric elements of the shortest telomere in a telomerase-negative cell influence the onset of senescence. We found that a 15 kb truncation of the 7L subtelomere widely used in studies of telomere biology affects cell growth when combined with telomerase inactivation. This effect is likely not explained by (i) elimination of sequence homology at chromosome ends that would compromise homology-directed DNA repair mechanisms; (ii) elimination of the conserved subtelomeric X-element; (iii) elimination of a gene that would become essential in the absence of telomerase; and (iv) heterochromatinization of inner genes, causing the silencing of an essential gene in replicative senescent cells. This works contributes to better delineate subtelomere functions and their impact on telomere biology.
Flexible controls of broadband electromagnetic wavefronts with a mechanically programmable metamaterial
Authors: Liu Shuo , Zhang Lei , Bai Guo Dong , Cui Tie Jun 
Published: February 2019

AbstractCoding and programmable metamaterials have experienced a rapid development since 2014, leading to many physical phenomena and engineering applications from microwave to terahertz frequencies, and even in the acoustic regime. The major challenge for current programmable metamaterials based on switching diodes is the experimental realization of a huge number of feeding lines for independent control of each digital unit. In this work, we provide an alternative approach for the experimental realization of the programmable metamaterial by developing a mechanical system, which consists of an array of metal blocks with adjustable height. The system supports the combination with conventional coding metamaterials to take full controls of both the phase and polarization of EM waves. As a theoretical byproduct of this work, we propose group delay code to achieve diffraction-limited achromatic redirection of linearly polarized broadband beam from 4 to 6 GHz by combining the group-delay code with the conventional phase code, a feat that traditionally requires complex structural design of unit cell. In view of the multifunctional performance afforded by the full-control of the phase, polarization and group delay, the mechanically controllable metamaterial in the microwave region may benefit different applications, such as imaging, communication, and radar detection.