bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repurposing endogenous immune pathways to tailor and control chimeric antigen receptor T cell functionality
Authors: Sachdeva Mohit , Busser Brian W. , Temburni Sonal , Jahangiri Billal , Gautron Anne-Sophie , Maréchal Alan , Juillerat Alexandre , Williams Alan , Depil Stéphane , Duchateau Philippe , Poirot Laurent , Valton Julien 
Published: November 2019

AbstractEndowing chimeric antigen receptor (CAR) T cells with additional potent functionalities holds strong potential for improving their antitumor activity. However, because potency could be deleterious without control, these additional features need to be tightly regulated. Immune pathways offer a wide array of tightly regulated genes that can be repurposed to express potent functionalities in a highly controlled manner. Here, we explore this concept by repurposing TCR, CD25 and PD1, three major players of the T cell activation pathway. We insert the CAR into the TCRα gene (TRACCAR), and IL-12P70 into either IL2Rα or PDCD1 genes. This process results in transient, antigen concentration-dependent IL-12P70 secretion, increases TRACCAR T cell cytotoxicity and extends survival of tumor-bearing mice. This gene network repurposing strategy can be extended to other cellular pathways, thus paving the way for generating smart CAR T cells able to integrate biological inputs and to translate them into therapeutic outputs in a highly regulated manner.
Picosecond to millisecond tracking of a photocatalytic decarboxylation reaction provides direct mechanistic insights
Authors: Bhattacherjee Aditi , Sneha Mahima , Lewis-Borrell Luke , Tau Omri , Clark Ian P. , Orr-Ewing Andrew J. 
Published: November 2019

AbstractThe photochemical decarboxylation of carboxylic acids is a versatile route to free radical intermediates for chemical synthesis. However, the sequential nature of this multi-step reaction renders the mechanism challenging to probe. Here, we employ a 100 kHz mid-infrared probe in a transient absorption spectroscopy experiment to track the decarboxylation of cyclohexanecarboxylic acid in acetonitrile-d3 over picosecond to millisecond timescales using a photooxidant pair (phenanthrene and 1,4-dicyanobenzene). Selective excitation of phenanthrene at 256 nm enables a diffusion-limited photoinduced electron transfer to 1,4-dicyanobenzene. A measured time offset in the rise of the CO2 byproduct reports on the lifetime (520 ± 120 ns) of a reactive carboxyl radical in solution, and spectroscopic observation of the carboxyl radical confirm its formation as a reaction intermediate. Precise clocking of the lifetimes of radicals generated in situ by an activated C-C bond fission will pave the way for improving the photocatalytic selectivity and turnover.
Room-temperature direct synthesis of semi-conductive PbS nanocrystal inks for optoelectronic applications
Authors: Wang Yongjie , Liu Zeke , Huo Nengjie , Li Fei , Gu Mengfan , Ling Xufeng , Zhang Yannan , Lu Kunyuan , Han Lu , Fang Honghua , Shulga Artem G. , Xue Ye , Zhou Sijie , Yang Fan , Tang Xun , Zheng Jiawei , Antonietta Loi Maria , Konstantatos Gerasimos , Ma Wanli 
Published: November 2019

AbstractLead sulphide (PbS) nanocrystals (NCs) are promising materials for low-cost, high-performance optoelectronic devices. So far, PbS NCs have to be first synthesized with long-alkyl chain organic surface ligands and then be ligand-exchanged with shorter ligands (two-steps) to enable charge transport. However, the initial synthesis of insulated PbS NCs show no necessity and the ligand-exchange process is tedious and extravagant. Herein, we have developed a direct one-step, scalable synthetic method for iodide capped PbS (PbS-I) NC inks. The estimated cost for PbS-I NC inks is decreased to less than 6 $·g−1, compared with 16 $·g−1 for conventional methods. Furthermore, based on these PbS-I NCs, photodetector devices show a high detectivity of 1.4 × 1011Jones and solar cells show an air-stable power conversion efficiency (PCE) up to 10%. This scalable and low-cost direct preparation of high-quality PbS-I NC inks may pave a path for the future commercialization of NC based optoelectronics.
Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers
Authors: Gopal Priyanka , Sarihan Elif Irem , Chie Eui Kyu , Kuzmishin Gwendolyn , Doken Semihcan , Pennell Nathan A. , Raymond Daniel P. , Murthy Sudish C. , Ahmad Usman , Raja Siva , Almeida Francisco , Sethi Sonali , Gildea Thomas R. , Peacock Craig D. , Adams Drew J. , Abazeed Mohamed E. 
Published: November 2019

AbstractMolecular determinants governing the evolution of tumor subclones toward phylogenetic branches or fixation remain unknown. Using sequencing data, we model the propagation and selection of clones expressing distinct categories ofBRAFmutations to estimate their evolutionary trajectories. We show that strongly activatingBRAFmutations demonstrate hard sweep dynamics, whereas mutations with less pronounced activation of the BRAF signaling pathway confer soft sweeps or are subclonal. We use clonal reconstructions to estimate the strength of “driver” selection in individual tumors. Using tumors cells and human-derived murine xenografts, we show that tumor sweep dynamics can significantly affect responses to targeted inhibitors of BRAF/MEK or DNA damaging agents. Our study uncovers patterns of distinctBRAFclonal evolutionary dynamics and nominates therapeutic strategies based on the identity of theBRAFmutation and its clonal composition.
Band splitting with vanishing spin polarizations in noncentrosymmetric crystals
Authors: Liu Kai , Luo Wei , Ji Junyi , Barone Paolo , Picozzi Silvia , Xiang Hongjun 
Published: November 2019

AbstractThe Dresselhaus and Rashba effects are well-known phenomena in solid-state physics, in which spin–orbit coupling splits spin-up and spin-down energy bands of nonmagnetic non-centrosymmetric crystals. Here, we discuss a phenomenon we dub band splitting with vanishing spin polarizations (BSVSP), in which, as usual, spin-orbit coupling splits the energy bands in nonmagnetic non-centrosymmetric systems. Surprisingly, however, both split bands show no net spin polarization along certain high-symmetry lines in the Brillouin zone. In order to rationalize this phenomenon, we propose a classification of point groups into pseudo-polar and non-pseudo-polar groups. By means of first-principles simulations, we demonstrate that BSVSP can take place in both symmorphic (e.g., bulk GaAs) and non-symmorphic systems (e.g., two dimensional ferroelectric SnTe). Furthermore, we identify a linear magnetoelectric coupling in reciprocal space, which could be employed to tune the spin polarization with an external electric field. The BSVSP effect and its manipulation could therefore form the basis for future spintronic devices.
Floodplain land cover affects biomass distribution of fish functional diversity in the Amazon River
Authors: Arantes Caroline C. , Winemiller Kirk O. , Asher Alex , Castello Leandro , Hess Laura L. , Petrere Miguel , Freitas Carlos E. C. 
Published: November 2019

AbstractLand-cover change often shifts the distribution of biomass in animal communities. However, the effects of land-cover changes on functional diversity remain poorly understood for many organisms and ecosystems, particularly, for floodplains. We hypothesize that the biomass distribution of fish functional diversity in floodplains is associated with land cover, which would imply that fish traits affect behavioral and/or demographic responses to gradients of land cover. Using data from surveys of 462 habitats covering a range of land-cover conditions in the Amazon River floodplain, we fitted statistical models to explain landscape-scale variation in functional diversity and biomass of all fish species as well as subsets of species possessing different functional traits. Forest cover was positively associated with fish biomass and the strength of this relationship varied according to functional groups defined by life history, trophic, migration, and swimming-performance/microhabitat-use traits. Forty-two percent of the functional groups, including those inferred to have enhanced feeding opportunities, growth, and/or reproductive success within forested habitats, had greater biomass where forest cover was greater. Conversely, the biomass of other functional groups, including habitat generalists and those that directly exploit autochthonous food resources, did not vary significantly in relation to forest cover. The niche space occupied by local assemblages (functional richness) and dispersion in trait abundances (functional dispersion) tended to increase with forest cover. Our study supports the expectation that deforestation in the Amazon River floodplain affects not only fish biomass but also functional diversity, with some functional groups being particularly vulnerable.
Quantitative PCR for leprosy diagnosis and monitoring in household contacts: A follow-up study, 2011–2018
Authors: Manta Fernanda S. N. , Barbieri Raquel R. , Moreira Suelen J. M. , Santos Paulo T. S. , Nery José A. C. , Duppre Nádia C. , Sales Anna M. , Pacheco Antônio G. , Hacker Mariana A. , Machado Alice M. , Sarno Euzenir N. , Moraes Milton O. 
Published: November 2019

AbstractHousehold contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6–290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.
Differences in alveolo-capillary equilibration in healthy subjects on facing O2 demand
Authors: Beretta Egidio , Grasso Gabriele Simone , Forcaia Greta , Sancini Giulio , Miserocchi Giuseppe 
Published: November 2019

AbstractOxygen diffusion across the air-blood barrier in the lung is commensurate with metabolic needs and ideally allows full equilibration between alveolar and blood partial oxygen pressures. We estimated the alveolo-capillary O2 equilibration in 18 healthy subjects at sea level at rest and after exposure to increased O2 demand, including work at sea level and on hypobaric hypoxia exposure at 3840 m (PA ~ 50 mmHg). For each subject we estimated O2 diffusion capacity (DO2), pulmonary capillary blood volume (Vc) and cardiac output ($$\dot{Q}$$Q̇). We derived blood capillary transit time $${\boldsymbol{(}}{\boldsymbol{T}}{\boldsymbol{t}}{\boldsymbol{=}}\frac{{\boldsymbol{V}}{\boldsymbol{c}}}{\dot{{\boldsymbol{Q}}}}{\boldsymbol{)}}$$(Tt=VcQ̇) and the time constant of the equilibration process ($${\boldsymbol{\tau }}{\boldsymbol{=}}\frac{{\boldsymbol{\beta }}{\boldsymbol{V}}{\boldsymbol{c}}}{{\boldsymbol{D}}{{\boldsymbol{O}}}_{{\boldsymbol{2}}}}$$τ=βVcDO2, β being the slope of the hemoglobin dissociation curve). O2 equilibration at the arterial end of the pulmonary capillary was defined as $${{\bf{L}}}_{{\bf{e}}{\bf{q}}}{\boldsymbol{=}}{{\bf{e}}}^{{\boldsymbol{-}}\frac{{\bf{T}}t}{{\boldsymbol{\tau }}}}$$Leq=e−Ttτ. Leq greately differed among subjects in the most demanding O2 condition (work in hypoxia): lack of full equilibration was found to range from 5 to 42% of the alveolo-capillary PO2 gradient at the venous end. The present analysis proves to be sensible enough to highlight inter-individual differences in alveolo-capillary equilibration among healthy subjects.
Quantitative description and classification of protein structures by a novel robust amino acid network: interaction selective network (ISN)
Authors: Konno Shohei , Namiki Takao , Ishimori Koichiro 
Published: November 2019

AbstractTo quantitatively categorize protein structures, we developed a quantitative coarse-grained model of protein structures with a novel amino acid network, the interaction selective network (ISN), characterized by the links based on interactions in both the main and side chains. We found that the ISN is a novel robust network model to show the higher classification probability in the plots of average vertex degree (k) versus average clustering coefficient (C), both of which are typical network parameters for protein structures, and successfully distinguished between “all-α” and “all-β” proteins. On the other hand, one of the typical conventional networks, the α-carbon network (CAN), was found to be less robust than the ISN, and another typical network, atomic distance network (ADN), failed to distinguish between these two protein structures. Considering that the links in the CAN and ADN are defined by the interactions only between the main chain atoms and by the distance of the closest atom pair between the two amino acid residues, respectively, we can conclude that reflecting structural information from both secondary and tertiary structures in the network parameters improves the quantitative evaluation and robustness in network models, resulting in a quantitative and more robust description of three-dimensional protein structures in the ISN.
Optimal efficiency of the Q-cycle mechanism around physiological temperatures from an open quantum systems approach
Authors: Tacchino Francesco , Succurro Antonella , Ebenhöh Oliver , Gerace Dario 
Published: November 2019

AbstractThe Q-cycle mechanism entering the electron and proton transport chain in oxygenic photosynthesis is an example of how biological processes can be efficiently investigated with elementary microscopic models. Here we address the problem of energy transport across the cellular membrane from an open quantum system theoretical perspective. We model the cytochrome $${b}_{6}\,f$$

b

6

f
protein complex under cyclic electron flow conditions starting from a simplified kinetic model, which is hereby revisited in terms of a Markovian quantum master equation formulation and spin-boson Hamiltonian treatment. We apply this model to theoretically demonstrate an optimal thermodynamic efficiency of the Q-cycle around ambient and physiologically relevant temperature conditions. Furthermore, we determine the quantum yield of this complex biochemical process after setting the electrochemical potentials to values well established in the literature. The present work suggests that the theory of quantum open systems can successfully push forward our theoretical understanding of complex biological systems working close to the quantum/classical boundary.
Multiplex analysis of 40 cytokines do not allow separation between endometriosis patients and controls
Authors: Knific Tamara , Fishman Dmytro , Vogler Andrej , Gstöttner Manuela , Wenzl René , Peterson Hedi , Rižner Tea Lanišnik 
Published: November 2019

AbstractEndometriosis is a common gynaecological condition characterized by severe pelvic pain and/or infertility. The combination of nonspecific symptoms and invasive laparoscopic diagnostics have prompted researchers to evaluate potential biomarkers that would enable a non-invasive diagnosis of endometriosis. Endometriosis is an inflammatory disease thus different cytokines represent potential diagnostic biomarkers. As panels of biomarkers are expected to enable better separation between patients and controls we evaluated 40 different cytokines in plasma samples of 210 patients (116 patients with endometriosis; 94 controls) from two medical centres (Slovenian, Austrian). Results of the univariate statistical analysis showed no differences in concentrations of the measured cytokines between patients and controls, confirmed by principal component analysis showing no clear separation amongst these two groups. In order to validate the hypothesis of a more profound (non-linear) differentiating dependency between features, machine learning methods were used. We trained four common machine learning algorithms (decision tree, linear model, k-nearest neighbour, random forest) on data from plasma levels of proteins and patients’ clinical data. The constructed models, however, did not separate patients with endometriosis from the controls with sufficient sensitivity and specificity. This study thus indicates that plasma levels of the selected cytokines have limited potential for diagnosis of endometriosis.
Clinicopathological values of PD-L1 expression in HER2-positive breast cancer
Authors: Kurozumi Sasagu , Inoue Kenichi , Matsumoto Hiroshi , Fujii Takaaki , Horiguchi Jun , Oyama Tetsunari , Kurosumi Masafumi , Shirabe Ken 
Published: November 2019

AbstractSeveral ongoing clinical trials are investigating the use of immuno-targeting therapy with programmed cell death protein-1 and programmed death-ligand 1 (PD-L1) inhibitors for triple-negative breast cancer. However, the role of PD-L1 expression in HER2-positive breast cancer remains unclear. We investigated the clinicopathological utility of PD-L1 expression in HER2-positive breast cancer. Cohort A included 248 patients with invasive breast cancer (all subtypes). Cohort B included 126 HER2-positive patients who received neoadjuvant chemotherapy (NAC) concomitant with trastuzumab. The relationship of PD-L1 expression on the cancer cells with clinicopathological factors including pathological complete response (pCR) and prognosis was investigated. In cohort A, 8.1% patients were PD-L1-positive; PD-L1 positivity showed a correlation with high degree of tumor-infiltrating lymphocytes (TILs), estrogen receptor negativity, progesterone receptor negativity, and high histological grade. In cohort B, 17.5% patients were PD-L1-positive; PD-L1 positivity showed a significant correlation with high degree of TILs and high abundance of CD8-positive TILs. The pCR rates were related to TILs and PD-L1 expression. Among PD-L1-negative patients, high CD8-positive TILs were associated with significantly better prognosis. In conclusion, 17.5% of HER2-positive type patients were PD-L1-positive. PD-L1 expression was associated with response to NAC with trastuzumab in patients with HER2-positive breast cancer.
Characterization of Matricellular Protein Expression Signatures in Mechanistically Diverse Mouse Models of Kidney Injury
Authors: Feng Daniel , Ngov Cindy , Henley Nathalie , Boufaied Nadia , Gerarduzzi Casimiro 
Published: November 2019

AbstractFibrosis is the most common pathophysiological manifestation of Chronic Kidney Disease (CKD). It is defined as excessive deposition of extracellular matrix (ECM) proteins. Embedded within the ECM are a family of proteins called Matricellular Proteins (MCPs), which are typically expressed during chronic pathologies for ECM processing. As such, identifying potential MCPs in the pathological secretome of a damaged kidney could serve as diagnostic/therapeutic targets of fibrosis. Using published RNA-Seq data from two kidney injury mouse models of different etiologies, Folic Acid (FA) and Unilateral Ureteral Obstruction (UUO), we compared and contrasted the expression profile of various members from well-known MCP families during the Acute and Fibrotic injury phases. As a result, we identified common and distinct MCP expression signatures between both injury models. Bioinformatic analysis of their differentially expressed MCP genes revealed similar top annotation clusters from Molecular Function and Biological Process networks, which are those commonly involved in fibrosis. Using kidney lysates from FA- and UUO-injured mice, we selected MCP genes from our candidate list to confirm mRNA expression by Western Blot, which correlated with injury progression. Understanding the expressions of MCPs will provide important insight into the processes of kidney repair, and may validate MCPs as biomarkers and/or therapeutic targets of CKD.
A strategy for quality evaluation of salt-treated Apocyni Veneti Folium and discovery of efficacy-associated markers by fingerprint-activity relationship modeling
Authors: Chen Cuihua , Chen Jiali , Shi Jingjing , Chen Shuyu , Zhao Hui , Yan Ying , Jiang Yucui , Gu Ling , Chen Feiyan , Liu Xunhong 
Published: November 2019

AbstractIn this study, a fingerprint-activity relationship between chemical fingerprints and hepatoprotective activity was established to evaluate the quality of salt-treated Apocyni Veneti Folium (AVF). Characteristic fingerprints of AVF samples exposed to different concentrations of salt were generated by ultrafast liquid chromatography tandem triple time-of-flight mass/mass spectrometry (UFLC-Triple TOF-MS/MS), and a similarity analysis was performed based on common characteristic peaks by hierarchical clustering analysis (HCA). Then, the hepatoprotective activity of AVF against CCl4-induced acute liver damage in mice was investigated by assessing biochemical markers and histopathology, which showed that a high dose of AVF exposed to low levels of salt stress produced a marked amelioration of hepatic damage compared with the other salt-treated AVF. Finally, fingerprint-activity relationship modeling, which was capable of discovering the bioactive markers used in the quality evaluation, was investigated by the chemical fingerprints and the hepatoprotective activities utilizing multivariate statistical analysis, gray correlation analysis (GCA) and bivariate correlation analysis (BCA). The results showed that the accumulation of polyphenols, such as flavonoids and phenolic acids, in AVF subjected to low levels of salt stress could result in the effective scavenging of free radicals. Therefore, the present study may provide a powerful strategy to holistically evaluate the quality of salt-treated AVF in combination with chemical fingerprint and bioactivity evaluation.
Standardised Framework for Quantitative Analysis of Fibrillation Dynamics
Authors: Li Xinyang , Roney Caroline H. , Handa Balvinder S. , Chowdhury Rasheda A. , Niederer Steven A. , Peters Nicholas S. , Ng Fu Siong 
Published: November 2019

AbstractThe analysis of complex mechanisms underlying ventricular fibrillation (VF) and atrial fibrillation (AF) requires sophisticated tools for studying spatio-temporal action potential (AP) propagation dynamics. However, fibrillation analysis tools are often custom-made or proprietary, and vary between research groups. With no optimal standardised framework for analysis, results from different studies have led to disparate findings. Given the technical gap, here we present a comprehensive framework and set of principles for quantifying properties of wavefront dynamics in phase-processed data recorded during myocardial fibrillation with potentiometric dyes. Phase transformation of the fibrillatory data is particularly useful for identifying self-perpetuating spiral waves or rotational drivers (RDs) rotating around a phase singularity (PS). RDs have been implicated in sustaining fibrillation, and thus accurate localisation and quantification of RDs is crucial for understanding specific fibrillatory mechanisms. In this work, we assess how variation of analysis parameters and thresholds in the tracking of PSs and quantification of RDs could result in different interpretations of the underlying fibrillation mechanism. These techniques have been described and applied to experimental AF and VF data, and AF simulations, and examples are provided from each of these data sets to demonstrate the range of fibrillatory behaviours and adaptability of these tools. The presented methodologies are available as an open source software and offer an off-the-shelf research toolkit for quantifying and analysing fibrillatory mechanisms.