bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors in patients with non-small cell lung cancer
Authors: Karayama M. , Masuda J. , Mori K. , Yasui H. , Hozumi H. , Suzuki Y. , Furuhashi K. , Fujisawa T. , Enomoto N. , Nakamura Y. , Inui N. , Suda T. , Maekawa M. , Sugimura H. , Takada A. 
Published: June 2020

Abstract
Purpose
Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity.

Methods
Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC).

Results
The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022).

Conclusions
Tryptophan metabolites may have a potential for predicting the efficacy of ICIs.

Registration number
University Hospital Medical Information Network Clinical Trial Registry 000026140.
A method for constructing sliding windows leak from noisy cache timing information
Authors: Ueno Rei , Takahashi Junko , Hayashi Yu-ichi , Homma Naofumi 
Published: June 2020

AbstractThis paper presents a method for constructing an operation sequence of sliding window exponentiation from the noisy cache information of RSA, which can be used for a cache attack using sliding windows leak (SWL). An SWL attack can retrieve the secret keys of RSA with non-negligible probability if the SWL is correctly captured. However, in practice, it is not always possible for an attacker to acquire a complete and correct operation sequence from cache information observation. In this paper, we first show that the capture errors in an operation sequence can be evaluated based on the Levenshtein distance between correct and estimated sequences. The dynamic time warping algorithm is employed for quantitative evaluation. Then, we present a method of accurately estimating a complete and correct operation sequence from noisy sequences obtained through multiple observations. Furthermore, we show the effectiveness of the proposed method through a set of experiments performed using RSA software in Libgcrypt. As a result, we can identify the correct operation sequence from approximately 100 observations of cache traces.
Corpus literacy instruction in language teacher education: Investigating Arab EFL student teachers’ immediate beliefs and long-term practices
Authors: Abdel Latif Muhammad M. M. 
Published: June 2020

AbstractWith the increasing recognition of the pedagogical applications of corpus linguistics, there has been a growing interest in developing teachers’ corpus literacy to popularize the use of corpora in language education. This longitudinal study investigated Arab Gulf EFL student teachers’ immediate and long-term responses to corpus literacy instruction. After teaching a corpus literacy component to two classes of student teachers in a graduate computer-assisted language learning course they attended, the author collected focus group data about their views on this instruction and their own expected future uses of corpora in language learning, teaching and research. Two years later, a group of these student teachers (n= 19) responded to a follow-up questionnaire exploring their beliefs about corpus literacy integration and their multiple uses of corpora. The student teachers reported very positive immediate and long-term perceptions of corpus literacy instruction, but it was found that such instruction has not brought about all the desired changes in their long-term uses of online corpora as a linguistic and pedagogical resource, or their attitudes towards doing corpus-based TESOL research. However, it is expected that the popularization benefits gained from corpus literacy integration could lead to better future developments in using corpora for language education and research purposes in the target context.
The Erber: tracing global trade through a London building
Authors: Milne Sarah A. 
Published: June 2020

AbstractThrough a case-study of one significant courtyard house owned by the Drapers’ Company and known as ‘The Erber’, this article argues that mercantile livery companies supported London's growing centrality within an expanding network of trade through the use and development of corporate properties. The micro-history at the heart of this article reveals that the ‘everyday’ built environment of sixteenth- and seventeenth-century London was shaped not just by the city elite. Also relevant to that process were the different sorts of tenants of the Drapers’ Company, who benefited from the expansion at all levels of London's mercantile activity. The trickle-down effects of global mercantilism affected spaces small and large. The investigation of the Erber highlights the domestic implications of global commercial expansion.
Soil Greenhouse Gas Fluxes From Maize Production Under Different Soil Fertility Management Practices in East Africa
Authors: Macharia Joseph M. , Pelster David E. , Ngetich Felix K. , Shisanya Chris A. , Mucheru‐Muna Monicah , Mugendi Daniel N. 
Published: June 2020

AbstractIn sub‐Saharan Africa (SSA), few studies have quantified greenhouse gas (GHG) emissions following application of soil amendments, for development of accurate national GHG inventories. Therefore, this study quantified soil GHG emissions using static chambers for two maize cropping seasons (one full year) of four different soil amendments in the central highlands of Kenya. The four treatments were (i) animal manure, (ii) inorganic fertilizer, (iii) combined animal manure and inorganic fertilizer, and (iv) a no‐N control (no amendment) laid out in a randomized complete block design. Cumulative annual soil fluxes (February 2017 to February 2018) ranged from −1.03 ± 0.19 kg CH4‐C ha−1 yr−1 from the manure inorganic fertilizer treatment to −0.09 ± 0.03 kg CH4‐C ha−1 yr−1 from the manure treatment, 1,391 ± 74 kg CO2‐C ha−1 yr−1 from the control treatment to 3,574 ± 113 kg CO2‐C ha−1 yr−1 from the manure treatment, and 0.13 ± 0.08 to 1.22 ± 0.12 kg N2O‐N ha−1 yr−1 in the control and manure treatments, respectively. Animal manure amendment produced the highest cumulative CO2 emissions (P < 0.001), N2O emissions (P < 0.001), and maize yields (P = 0.002) but the lowest N2O yield‐scaled emission (YSE) (0.5 g N2O–N kg−1 grain yield). Manure combined with inorganic fertilizer had the highest cumulative CH4 uptake (P < 0.001) and N2O YSE (2.2 g N2O–N kg−1 grain yield). Our results indicate that while the use of animal manure may increase total GHG emissions, the concurrent increase in maize yields results in reduced yield‐scaled GHG emissions.
Different Peak Response Time of Daytime Thermospheric Neutral Species to the 27‐Day Solar EUV Flux Variations
Authors: Ren Dexin , Lei Jiuhou , Wang Wenbin , Burns Alan , Luan Xiaoli , Dou Xiankang 
Published: June 2020

AbstractPrevious work suggested that the peak response time of the mass densities of atomic oxygen (O) and molecular nitrogen (N2) in the thermosphere had more than a 1‐day difference relative to the peak of the 27‐day periodic variation of solar extreme ultraviolet (EUV) flux. In this study, we used the Thermosphere Ionosphere Electrodynamic General Circulation Model (TIEGCM) to explore the physical mechanisms responsible for the different peak response times of the daytime thermospheric neutral species. It was found that the peak response time of O or N2 mass density corresponds to the time of equilibrium between the contributions from the barometric effect and the change in its abundance. The peak response time of O is shorter than that of thermospheric temperature Tn, due to a dynamic change in the circulation that acts to cancel out the contribution from the barometric process prior to the peak of Tn. On the contrary, the change of N2 abundance contributes further to a decrease of N2 mass density on a constant pressure surface when the thermosphere is expanding. The change of chemical loss leads to a longer peak response time of N2 abundance than that due to barometric motion. Therefore, an equilibrium is reached after the barometric effect turns from expansion (contraction) to contraction (expansion), so that the peak response time of N2 is longer than that of Tn. Moreover, the meridional circulation in the thermosphere modulates the latitudinal dependence of the peak response time of thermospheric neutral species.
Biochemical activity of RAGs is impeded by Dolutegravir, an HIV integrase inhibitor
Authors: Nilavar Namrata M. , Paranjape Amita M. , Raghavan Sathees C. 
Published: June 2020

AbstractHIV is a retrovirus that infects CD4+ T lymphocytes in human beings and causes immunodeficiency. In the recent years, various therapies have been developed against HIV, including targeting the HIV specific protein, integrase, responsible for integration of HIV cDNA into host DNA. Although, integrase is specific to HIV, it has functional and structural similarity with RAG1, one of the partner proteins associated with V(D)J recombination, a process by which immune diversity is generated in humans. Currently, there are three HIV integrase inhibitors: Elvitegravir, Dolutegravir, and Raltegravir, in the market which have been approved by the FDA (USA). All three drugs are used in anti-retroviral therapy (ART). Previously, we showed that amongst the HIV inhibitors, Elvitegravir could significantly decrease B cell maturation in vivo and inhibit the physiological activities of RAGs in vitro, unlike Raltegravir. In the present study, we address the effect of second-generation integrase inhibitor, Dolutegravir on RAG activities. Binding and nicking studies showed that, Dolutegravir could decrease the binding efficiency of RAG1 domains and cleavage on DNA substrates, but not as considerably as Elvitegravir. Thus, we show that although the integrase inhibitors such as Elvitegravir show an affinity towards RAG1, the newer molecules may have lesser side-effects.
Nuclear interacting SET domain protein 1 inactivation impairs GATA1-regulated erythroid differentiation and causes erythroleukemia
Authors: Leonards Katharina , Almosailleakh Marwa , Tauchmann Samantha , Bagger Frederik Otzen , Thirant Cécile , Juge Sabine , Bock Thomas , Méreau Hélène , Bezerra Matheus F. , Tzankov Alexandar , Ivanek Robert , Losson Régine , Peters Antoine H. F. M. , Mercher Thomas , Schwaller Juerg 
Published: June 2020

AbstractThe nuclear receptor binding SET domain protein 1 (NSD1) is recurrently mutated in human cancers including acute leukemia. We show that NSD1 knockdown alters erythroid clonogenic growth of human CD34+hematopoietic cells. Ablation ofNsd1in the hematopoietic system of mice induces a transplantable erythroleukemia. In vitro differentiation ofNsd1−/−erythroblasts is majorly impaired despite abundant expression of GATA1, the transcriptional master regulator of erythropoiesis, and associated with an impaired activation of GATA1-induced targets. Retroviral expression of wildtype NSD1, but not a catalytically-inactive NSD1N1918QSET-domain mutant induces terminal maturation ofNsd1−/−erythroblasts. Despite similar GATA1 protein levels, exogenous NSD1 but not NSDN1918Qsignificantly increases the occupancy of GATA1 at target genes and their expression. Notably, exogenous NSD1 reduces the association of GATA1 with the co-repressor SKI, and knockdown of SKI induces differentiation ofNsd1−/−erythroblasts. Collectively, we identify the NSD1 methyltransferase as a regulator of GATA1-controlled erythroid differentiation and leukemogenesis.
Water stable molecular n-doping produces organic electrochemical transistors with high transconductance and record stability
Authors: Paterson Alexandra F. , Savva Achilleas , Wustoni Shofarul , Tsetseris Leonidas , Paulsen Bryan D. , Faber Hendrik , Emwas Abdul Hamid , Chen Xingxing , Nikiforidis Georgios , Hidalgo Tania C. , Moser Maximillian , Maria Iuliana Petruta , Rivnay Jonathan , McCulloch Iain , Anthopoulos Thomas D. , Inal Sahika 
Published: June 2020

AbstractFrom established to emergent technologies, doping plays a crucial role in all semiconducting devices. Doping could, theoretically, be an excellent technique for improving repressively low transconductances in n-type organic electrochemical transistors – critical for advancing logic circuits for bioelectronic and neuromorphic technologies. However, the technical challenge is extreme: n-doped polymers are unstable in electrochemical transistor operating environments, air and water (electrolyte). Here, the first demonstration of doping in electron transporting organic electrochemical transistors is reported. The ammonium salt tetra-n-butylammonium fluoride is simply admixed with the conjugated polymer poly(N,N’-bis(7-glycol)-naphthalene-1,4,5,8-bis(dicarboximide)-co-2,2’-bithiophene-co-N,N’-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide), and found to act as a simultaneous molecular dopant and morphology-additive. The combined effects enhance the n-type transconductance with improved channel capacitance and mobility. Furthermore, operational and shelf-life stability measurements showcase the first example of water-stable n-doping in a polymer. Overall, the results set a precedent for doping/additives to impact organic electrochemical transistors as powerfully as they have in other semiconducting devices.
Functional annotation of rare structural variation in the human brain
Authors: Han Lide , Zhao Xuefang , Benton Mary Lauren , Perumal Thaneer , Collins Ryan L. , Hoffman Gabriel E. , Johnson Jessica S. , Sloofman Laura , Wang Harold Z. , Stone Matthew R. ,   CommonMind Consortium, Akbarian Schahram , Bendl Jaroslav , Breen Michael , Brennand Kristen J. , Brown Leanne , Browne Andrew , Buxbaum Joseph D. , Charney Alexander , Chess Andrew , Couto Lizette , Crawford Greg , Devillers Olivia , Devlin Bernie , Dobbyn Amanda , Domenici Enrico , Filosi Michele , Flatow Elie , Francoeur Nancy , Fullard John , Gil Sergio Espeso , Girdhar Kiran , Gulyás-Kovács Attila , Gur Raquel , Hahn Chang-Gyu , Haroutunian Vahram , Hauberg Mads Engel , Huckins Laura , Jacobov Rivky , Jiang Yan , Johnson Jessica S. , Kassim Bibi , Kim Yungil , Klei Lambertus , Kramer Robin , Lauria Mario , Lehner Thomas , Lewis David A. , Lipska Barbara K. , Montgomery Kelsey , Park Royce , Rosenbluh Chaggai , Roussos Panos , Ruderfer Douglas M. , Senthil Geetha , Shah Hardik R. , Sloofman Laura , Song Lingyun , Stahl Eli , Sullivan Patrick , Visintainer Roberto , Wang Jiebiao , Wang Ying-Chih , Wiseman Jennifer , Xia Eva , Zhang Wen , Zharovsky Elizabeth , Brennand Kristen J. , Brand Harrison , Sieberts Solveig K. , Marenco Stefano , Peters Mette A. , Lipska Barbara K. , Roussos Panos , Capra John A. , Talkowski Michael , Ruderfer Douglas M. 
Published: June 2020

AbstractStructural variants (SVs) contribute to many disorders, yet, functionally annotating them remains a major challenge. Here, we integrate SVs with RNA-sequencing from human post-mortem brains to quantify their dosage and regulatory effects. We show that genic and regulatory SVs exist at significantly lower frequencies than intergenic SVs. Functional impact of copy number variants (CNVs) stems from both the proportion of genic and regulatory content altered and loss-of-function intolerance of the gene. We train a linear model to predict expression effects of rare CNVs and use it to annotate regulatory disruption of CNVs from 14,891 independent genome-sequenced individuals. Pathogenic deletions implicated in neurodevelopmental disorders show significantly more extreme regulatory disruption scores and if rank ordered would be prioritized higher than using frequency or length alone. This work shows the deleteriousness of regulatory SVs, particularly those altering CTCF sites and provides a simple approach for functionally annotating the regulatory consequences of CNVs.
Heavy N+ ion transfer in doubly charged N2Ar van der Waals cluster
Authors: Zhu XiaoLong , Hu XiaoQing , Yan ShunCheng , Peng YiGeng , Feng WenTian , Guo DaLong , Gao Yong , Zhang ShaoFeng , Cassimi Amine , Xu JiaWei , Zhao DongMei , Dong DaPu , Hai Bang , Wu Yong , Wang JianGuo , Ma X. 
Published: June 2020

AbstractVan der Waals clusters are weakly bound atomic/molecular systems and are an important medium for understanding micro-environmental chemical phenomena in bio-systems. The presence of neighboring atoms may open channels otherwise forbidden in isolated atoms/molecules. In hydrogen-bond clusters, proton transfer plays a crucial role, which involves mass and charge migration over large distances within the cluster and results in its fragmentation. Here we report an exotic transfer channel involving a heavy N+ ion observed in a doubly charged cluster produced by 1 MeV Ne8+ ions: (N2Ar)2+→N++NAr+. The neighboring Ar atom decreases the $${\mathrm{N}}_2^{2 + }$$

N

2

2
+

barrier height and width, resulting in significant shorter lifetimes of the metastable molecular ion state $${\mathrm{N}}_2^{2 + }$$

N

2

2
+

($${{\mathrm{X}}^{1}}{\Sigma _{{\mathrm{g}}}^{+}}$$

X

1

Σ

g

+

). Consequently, the breakup of the covalent N+−N+ bond, the tunneling out of the N+ ion from the $${\mathrm{N}}_2^{2 + }$$

N

2

2
+

potential well, as well as the formation of an N−Ar+ bound system take place almost simultaneously, resulting in a Coulomb explosion of N+ and NAr+ ion pairs.
ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages
Authors: Yin Jinlong , Kim Sung Soo , Choi Eunji , Oh Young Taek , Lin Weiwei , Kim Tae-Hoon , Sa Jason K. , Hong Jun Hee , Park Se Hwan , Kwon Hyung Joon , Jin Xiong , You Yeonhee , Kim Ji Hye , Kim Hyunggee , Son Jaekyoung , Lee Jeongwu , Nam Do-Hyun , Choi Kui Son , Shi Bingyang , Gwak Ho-Shin , Yoo Heon , Iavarone Antonio , Kim Jong Heon , Park Jong Bae 
Published: June 2020

AbstractThe interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E2 (PGE2), which stimulates β-catenin activation of GSC and M2-like TAM polarization. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE2 production. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.
Autophagy controls the induction and developmental decline of NMDAR-LTD through endocytic recycling
Authors: Shen Hongmei , Zhu Huiwen , Panja Debabrata , Gu Qinhua , Li Zheng 
Published: June 2020

AbstractNMDA receptor-dependent long-term depression (NMDAR-LTD) is a long-lasting form of synaptic plasticity. Its expression is mediated by the removal of AMPA receptors from postsynaptic membranes. Under basal conditions, endocytosed AMPA receptors are rapidly recycled back to the plasma membrane. In NMDAR-LTD, however, they are diverted to late endosomes for degradation. The mechanism for this switch is largely unclear. Additionally, the inducibility of NMDAR-LTD is greatly reduced in adulthood. The underlying mechanism and physiological significance of this phenomenon are elusive. Here, we report that autophagy inhibition is essential for the induction and developmental dampening of NMDAR-LTD. Autophagy is inhibited during NMDAR-LTD to decrease endocytic recycling. Autophagy inhibition is both necessary and sufficient for LTD induction. In adulthood, autophagy is up-regulated to make LTD induction harder, thereby preventing the adverse effect of excessive LTD on memory consolidation. These findings reveal the unrecognized functions of autophagy in synaptic plasticity, endocytic recycling, and memory.
Angiopoietin-2–integrin α5β1 signaling enhances vascular fatty acid transport and prevents ectopic lipid-induced insulin resistance
Authors: Bae Hosung , Hong Ki Yong , Lee Choong-kun , Jang Cholsoon , Lee Seung-Jun , Choe Kibaek , Offermanns Stefan , He Yulong , Lee Hyuek Jong , Koh Gou Young 
Published: June 2020

AbstractProper storage of excessive dietary fat into subcutaneous adipose tissue (SAT) prevents ectopic lipid deposition-induced insulin resistance, yet the underlying mechanism remains unclear. Here, we identify angiopoietin-2 (Angpt2)–integrin α5β1 signaling as an inducer of fat uptake specifically in SAT. Adipocyte-specific deletion of Angpt2 markedly reduced fatty acid uptake and storage in SAT, leading to ectopic lipid accumulation in glucose-consuming organs including skeletal muscle and liver and to systemic insulin resistance. Mechanistically, Angpt2 activated integrin α5β1 signaling in the endothelium and triggered fatty acid transport via CD36 and FATP3 into SAT. Genetic or pharmacological inhibition of the endothelial integrin α5β1 recapitulated adipocyte-specific Angpt2 knockout phenotypes. Our findings demonstrate the critical roles of Angpt2–integrin α5β1 signaling in SAT endothelium in regulating whole-body fat distribution for metabolic health and highlight adipocyte–endothelial crosstalk as a potential target for prevention of ectopic lipid deposition-induced lipotoxicity and insulin resistance.
Robust leaf trait relationships across species under global environmental changes
Authors: Cui Erqian , Weng Ensheng , Yan Enrong , Xia Jianyang 
Published: June 2020

AbstractRecent studies show coordinated relationships between plant leaf traits and their capacity to predict ecosystem functions. However, how leaf traits will change within species and whether interspecific trait relationships will shift under future environmental changes both remain unclear. Here, we examine the bivariate correlations between leaf economic traits of 515 species in 210 experiments which mimic climate warming, drought, elevated CO2, and nitrogen deposition. We find divergent directions of changes in trait-pairs between species, and the directions mostly do not follow the interspecific trait relationships. However, the slopes in the logarithmic transformed interspecific trait relationships hold stable under environmental changes, while only their elevations vary. The elevation changes of trait relationship are mainly driven by asymmetrically interspecific responses contrary to the direction of the leaf economic spectrum. These findings suggest robust interspecific trait relationships under global changes, and call for linking within-species responses to interspecific coordination of plant traits.