bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective Effects of Human Liver Stem Cell-Derived Extracellular Vesicles in a Mouse Model of Hepatic Ischemia-Reperfusion Injury
Authors: Calleri Alberto , Roggio Dorotea , Navarro-Tableros Victor , De Stefano Nicola , Pasquino Chiara , David Ezio , Frigatti Giada , Rigo Federica , Antico Federica , Caropreso Paola , Patrono Damiano , Bruno Stefania , Romagnoli Renato 
Published: December 2020

AbstractHepatic ischemia-reperfusion injury (IRI) is observed in liver transplantation and hepato-biliary surgery and is associated with an inflammatory response. Human liver stem cell-derived extracellular vesicles (HLSC-EV) have been demonstrated to reduce liver damage in different experimental settings by accelerating regeneration and by modulating inflammation. The aim of the present study was to investigate whether HLSC-EV may protect liver from IRI in a mouse experimental model. Segmental IRI was obtained by selective clamping of intrahepatic pedicles for 90 min followed by 6 h of reperfusion. HLSC-EV were administered intravenously at the end of the ischemic period and histopathological and biochemical alterations were evaluated in comparison with controls injected with vehicle alone. Intra liver localization of labeled HLSC-EV was assessed by in in vivo Imaging System (IVIS) and the internalization into hepatocytes was confirmed by fluorescence analyses. As compared to the control group, administration of 3 × 109 particles (EV1 group) significantly reduced alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) release, necrosis extension and cytokines expression (TNF-α, CCL-2 and CXCL-10). However, the administration of an increased dose of HLSC-EV (7.5 × 109 particles, EV2 group) showed no significant improvement in respect to controls at enzyme and histology levels, despite a significantly lower cytokine expression. In conclusion, this study demonstrated that 3 × 109 HLSC-EV were able to modulate hepatic IRI by preserving tissue integrity and by reducing transaminases release and inflammatory cytokines expression. By contrast, a higher dose was ineffective suggesting a restricted window of biological activity.
High temperature tribological behaviour of PVD coated tool steel and aluminium under dry and lubricated conditions
Authors: Decrozant-Triquenaux Justine , Pelcastre Leonardo , Courbon Cédric , Prakash Braham , Hardell Jens 
Published: December 2020

AbstractAluminium alloys are commonly used as lightweight materials in the automotive industry. This non-ferrous family of metallic alloys offers a high versatility of properties and designs. To reduce weight and improve safety, high strength-to-weight ratio alloys (e.g. 6XXX and 7XXX), are increasingly implemented in vehicles. However, these alloys exhibit low formability and experience considerable springback during cold forming, and are therefore hot formed. During forming, severe adhesion (i.e. galling) of aluminium onto the die surface takes place. This phenomenon has a detrimental effect on the surface properties, geometrical tolerances of the formed parts and maintenance of the dies. The effect of surface engineering as well as lubricant chemistry on galling has not been sufficiently investigated. Diamond-like carbon (DLC) and CrN physical vapour deposition (PVD) coated steel have been studied to reduce aluminium transfer. However, the interaction between lubricants and PVD coatings during hot forming of aluminium alloys is not yet fully understood. The present study thus aims to characterise the high temperature tribological behaviour of selected PVD coatings and lubricants during sliding against aluminium alloy. The objectives are to first select promising lubricant-coating combinations and then to study their tribological response in a high-temperature reciprocating friction and wear tester. Dry and lubricated tests were carried out at 300 °C using a commercial polymer lubricant. Tests using DLC, CrN, CrTiN, and CrAlN coated tool steel were compared to uncoated tool steel reference tests. The initial and worn test specimen surfaces were analysed with a 3-dimensional (3D) optical profiler, scanning electron microscope (SEM) and energy dispersive X-ray spectroscope (EDS) as to understand the wear mechanisms. The results showed formation of tribolayers in the contact zone, reducing both friction and wear. The stability of these layers highly depends on both the coatings’ roughness and chemical affinity towards aluminium. The DLC and CrN coatings combined with the polymer lubricant were the most effective in reducing aluminium transfer.
Stability analysis of long hydrodynamic journal bearings based on the journal center trajectory
Authors: Huang Yu , Cao Haiyin , Tian Zhuxin 
Published: December 2020

AbstractIn this study, we observe that there are two threshold speeds (stability threshold speed and second threshold speed) for the long journal bearing, which is different for the short bearing. When the rotating speed is below the stability threshold speed, the stability boundary nearly coincides with the clearance circle, and the journal center gradually returns to the equilibrium point after being released at an initial point. If the rotating speed is between the stability threshold speed and the second threshold speed, after being released at an initial point, the journal center converges to a contour containing the equilibrium point. In this situation, for a higher rotating speed, the corresponding contour is also larger. When the rotating speed exceeds the second threshold speed, the journal gradually moves towards the bearing surface after being released at an initial point.
Can We Make the European Fundamental Freedoms Less Constraining? A Literature Review
Authors: HÖPNER Martin , SCHMIDT Susanne K. 
Published: December 2020

AbstractThis article reviews the legal and political science literatures on the extensive interpretation of the European fundamental freedoms and on possible ways out. The common market rules were originally laid down in an international treaty, the Treaty of Rome. In functional terms, this treaty became ade factoconstitution, implying that its content, including the fundamental freedoms, were constitutionalised. We review how this constitutionalisation constrains legislators at the Member State and European levels. In order to identify possible ways out, we also review several reform options: institutional reforms of the European judicial system; the de-constitutionalisation of the fundamental freedoms; counterbalancing these freedoms with further strengthened social rights; and contestation of over-constitutionalisation within the given primary law framework. We conclude that reform options are available that could gradually free the legislators from the over-constitutionalisation of the common market rules. Such options should become part of the ‘Conference on the Future of Europe’ process and debates about EU reforms in general, as more flexibility is warranted in a heterogeneous EU.
-MINIMUM SPANNING LENGTHS AND AN EXTENSION TO BURNSIDE’S THEOREM ON IRREDUCIBILITY
Authors: LONGSTAFF W. E. 
Published: December 2020

AbstractWe introduce the

$\textbf{h}$
-minimum spanning length of a family

${\mathcal A}$
of

$n\times n$
matrices over a field

$\mathbb F$
, where

$\textbf{h}$
is a p-tuple of positive integers, each no more than n. For an algebraically closed field

$\mathbb F$
, Burnside’s theorem on irreducibility is essentially that the

$(n,n,\ldots ,n)$
-minimum spanning length of

${\mathcal A}$
exists if

${\mathcal A}$
is irreducible. We show that the

$\textbf{h}$
-minimum spanning length of

${\mathcal A}$
exists for every

$\textbf{h}=(h_1,h_2,\ldots , h_p)$
if

${\mathcal A}$
is an irreducible family of invertible matrices with at least three elements. The

$(1,1, \ldots ,1)$
-minimum spanning length is at most

$4n\log _{2} 2n+8n-3$
. Several examples are given, including one giving a complete calculation of the

$(p,q)$
-minimum spanning length of the ordered pair

$(J^*,J)$
, where J is the Jordan matrix.
Shaping of the 3D genome by the ATPase machine cohesin
Authors: Kim Yoori , Yu Hongtao 
Published: December 2020

AbstractThe spatial organization of the genome is critical for fundamental biological processes, including transcription, genome replication, and segregation. Chromatin is compacted and organized with defined patterns and proper dynamics during the cell cycle. Aided by direct visualization and indirect genome reconstruction tools, recent discoveries have advanced our understanding of how interphase chromatin is dynamically folded at the molecular level. Here, we review the current understanding of interphase genome organization with a focus on the major regulator of genome structure, the cohesin complex. We further discuss how cohesin harnesses the energy of ATP hydrolysis to shape the genome by extruding chromatin loops.
Emerging immunotherapies for metastasis
Authors: Edwards Sarah C. , Hoevenaar Wilma H. M. , Coffelt Seth B. 
Published: December 2020

AbstractMajor advances in cancer immunotherapy have dramatically expanded the potential to manipulate immune cells in cancer patients with metastatic disease to counteract cancer spread and extend patient lifespan. One of the most successful types of immunotherapy is the immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1, that keep anti-tumour T cells active. However, not every patient with metastatic disease benefits from this class of drugs and patients often develop resistance to these therapies over time. Tremendous research effort is now underway to uncover new immunotherapeutic targets that can be used in patients who are refractory to anti-CTLA-4 or anti-PD-1 treatment. Here, we discuss results from experimental model systems demonstrating that modulating the immune response can negatively affect metastasis formation. We focus on molecules that boost anti-tumour immune cells and opportunities to block immunosuppression, as well as cell-based therapies with enhanced tumour recognition properties for solid tumours. We also present a list of challenges in treating metastatic disease with immunotherapy that must be considered in order to move laboratory observations into clinical practice and maximise patient benefit.
Endocytosis: a pivotal pathway for regulating metastasis
Authors: Khan Imran , Steeg Patricia S. 
Published: December 2020

AbstractA potentially important aspect in the regulation of tumour metastasis is endocytosis. This process consists of internalisation of cell-surface receptors via pinocytosis, phagocytosis or receptor-mediated endocytosis, the latter of which includes clathrin-, caveolae- and non-clathrin or caveolae-mediated mechanisms. Endocytosis then progresses through several intracellular compartments for sorting and routing of cargo, ending in lysosomal degradation, recycling back to the cell surface or secretion. Multiple endocytic proteins are dysregulated in cancer and regulate tumour metastasis, particularly migration and invasion. Importantly, four metastasis suppressor genes function in part by regulating endocytosis, namely, the NME, KAI, MTSS1 and KISS1 pathways. Data on metastasis suppressors identify a new point of dysregulation operative in tumour metastasis, alterations in signalling through endocytosis. This review will focus on the multicomponent process of endocytosis affecting different steps of metastasis and how metastatic-suppressor genes use endocytosis to suppress metastasis.
The stress-responsive kinase DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress
Authors: Moreno Rita , Banerjee Sourav , Jackson Angus W. , Quinn Jean , Baillie Gregg , Dixon Jack E. , Dinkova-Kostova Albena T. , Edwards Joanne , de la Vega Laureano 
Published: December 2020

AbstractTo survive proteotoxic stress, cancer cells activate the proteotoxic-stress response pathway, which is controlled by the transcription factor heat shock factor 1 (HSF1). This pathway supports cancer initiation, cancer progression and chemoresistance and thus is an attractive therapeutic target. As developing inhibitors against transcriptional regulators, such as HSF1 is challenging, the identification and targeting of upstream regulators of HSF1 present a tractable alternative strategy. Here we demonstrate that in triple-negative breast cancer (TNBC) cells, the dual specificity tyrosine-regulated kinase 2 (DYRK2) phosphorylates HSF1, promoting its nuclear stability and transcriptional activity. DYRK2 depletion reduces HSF1 activity and sensitises TNBC cells to proteotoxic stress. Importantly, in tumours from TNBC patients, DYRK2 levels positively correlate with active HSF1 and associates with poor prognosis, suggesting that DYRK2 could be promoting TNBC. These findings identify DYRK2 as a key modulator of the HSF1 transcriptional programme and a potential therapeutic target.
Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity
Authors: Agarwal Vineet , Venkatakrishnan A. J. , Puranik Arjun , Kirkup Christian , Lopez-Marquez Agustin , Challener Douglas W. , Theel Elitza S. , O’Horo John C. , Binnicker Matthew J. , Kremers Walter K. , Faubion William A. , Badley Andrew D. , Williams Amy W. , Gores Gregory J. , Halamka John D. , Morice William G. , Soundararajan Venky 
Published: December 2020

AbstractLongitudinal characterization of SARS-CoV-2 PCR testing from COVID-19 patient’s nasopharynx and its juxtaposition with blood-based IgG-seroconversion diagnostic assays is critical to understanding SARS-CoV-2 infection durations. Here, we retrospectively analyze 851 SARS-CoV-2-positive patients with at least two positive PCR tests and find that 99 of these patients remain SARS-CoV-2-positive after 4 weeks from their initial diagnosis date. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95% CI: 34.3–41.3). Our findings from juxtaposing IgG and PCR tests thus reveal that some SARS-CoV-2-positive patients are non-hospitalized and seropositive, yet actively shed viral RNA (14 of 90 patients). This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term non-hospitalized shedders as a means of characterizing the SARS-CoV-2 infection lifecycle.
Laser-driven x-ray and proton micro-source and application to simultaneous single-shot bi-modal radiographic imaging
Authors: Ostermayr T. M. , Kreuzer C. , Englbrecht F. S. , Gebhard J. , Hartmann J. , Huebl A. , Haffa D. , Hilz P. , Parodi K. , Wenz J. , Donovan M. E. , Dyer G. , Gaul E. , Gordon J. , Martinez M. , Mccary E. , Spinks M. , Tiwari G. , Hegelich B. M. , Schreiber J. 
Published: December 2020

AbstractRadiographic imaging with x-rays and protons is an omnipresent tool in basic research and applications in industry, material science and medical diagnostics. The information contained in both modalities can often be valuable in principle, but difficult to access simultaneously. Laser-driven solid-density plasma-sources deliver both kinds of radiation, but mostly single modalities have been explored for applications. Their potential for bi-modal radiographic imaging has never been fully realized, due to problems in generating appropriate sources and separating image modalities. Here, we report on the generation of proton and x-ray micro-sources in laser-plasma interactions of the focused Texas Petawatt laser with solid-density, micrometer-sized tungsten needles. We apply them for bi-modal radiographic imaging of biological and technological objects in a single laser shot. Thereby, advantages of laser-driven sources could be enriched beyond their small footprint by embracing their additional unique properties, including the spectral bandwidth, small source size and multi-mode emission.
A nanobody suite for yeast scaffold nucleoporins provides details of the nuclear pore complex structure
Authors: Nordeen Sarah A. , Andersen Kasper R. , Knockenhauer Kevin E. , Ingram Jessica R. , Ploegh Hidde L. , Schwartz Thomas U. 
Published: December 2020

AbstractNuclear pore complexes (NPCs) are the main conduits for molecular exchange across the nuclear envelope. The NPC is a modular assembly of ~500 individual proteins, called nucleoporins or nups. Most scaffolding nups are organized in two multimeric subcomplexes, the Nup84 or Y complex and the Nic96 or inner ring complex. Working in S. cerevisiae, and to study the assembly of these two essential subcomplexes, we here develop a set of twelve nanobodies that recognize seven constituent nucleoporins of the Y and Nic96 complexes. These nanobodies all bind specifically and with high affinity. We present structures of several nup-nanobody complexes, revealing their binding sites. Additionally, constitutive expression of the nanobody suite in S. cerevisiae detect accessible and obstructed surfaces of the Y complex and Nic96 within the NPC. Overall, this suite of nanobodies provides a unique and versatile toolkit for the study of the NPC.
Identification and characterization of constrained non-exonic bases lacking predictive epigenomic and transcription factor binding annotations
Authors: Grujic Olivera , Phung Tanya N. , Kwon Soo Bin , Arneson Adriana , Lee Yuju , Lohmueller Kirk E. , Ernst Jason 
Published: December 2020

AbstractAnnotations of evolutionary sequence constraint based on multi-species genome alignments and genome-wide maps of epigenomic marks and transcription factor binding provide important complementary information for understanding the human genome and genetic variation. Here we developed the Constrained Non-Exonic Predictor (CNEP) to quantify the evidence of each base in the genome being in an evolutionarily constrained non-exonic element from an input of over 60,000 epigenomic and transcription factor binding features. We find that the CNEP score outperforms baseline and related existing scores at predicting evolutionarily constrained non-exonic bases from such data. However, a subset of them are still not well predicted by CNEP. We developed a complementary Conservation Signature Score by CNEP (CSS-CNEP) that is predictive of those bases. We further characterize the nature of constrained non-exonic bases with low CNEP scores using additional types of information. CNEP and CSS-CNEP are resources for analyzing constrained non-exonic bases in the genome.
The CCR4–NOT deadenylase complex safeguards thymic positive selection by down-regulating aberrant pro-apoptotic gene expression
Authors: Ito-Kureha Taku , Miyao Takahisa , Nishijima Saori , Suzuki Toru , Koizumi Shin-ichi , Villar-Briones Alejandro , Takahashi Akinori , Akiyama Nobuko , Morita Masahiro , Naguro Isao , Ishikawa Hiroki , Ichijo Hidenori , Akiyama Taishin , Yamamoto Tadashi 
Published: December 2020

AbstractA repertoire of T cells with diverse antigen receptors is selected in the thymus. However, detailed mechanisms underlying this thymic positive selection are not clear. Here we show that the CCR4-NOT complex limits expression of specific genes through deadenylation of mRNA poly(A) tails, enabling positive selection. Specifically, the CCR4-NOT complex is up-regulated in thymocytes before initiation of positive selection, where in turn, it inhibits up-regulation of pro-apoptotic Bbc3 and Dab2ip. Elimination of the CCR4-NOT complex permits up-regulation of Bbc3 during a later stage of positive selection, inducing thymocyte apoptosis. In addition, CCR4-NOT elimination up-regulates Dab2ip at an early stage of positive selection. Thus, CCR4-NOT might control thymocyte survival during two-distinct stages of positive selection by suppressing expression levels of pro-apoptotic molecules. Taken together, we propose a link between CCR4-NOT-mediated mRNA decay and T cell selection in the thymus.
Structural modularity of the XIST ribonucleoprotein complex
Authors: Lu Zhipeng , Guo Jimmy K. , Wei Yuning , Dou Diana R. , Zarnegar Brian , Ma Qing , Li Rui , Zhao Yang , Liu Fan , Choudhry Hani , Khavari Paul A. , Chang Howard Y. 
Published: December 2020

AbstractLong noncoding RNAs are thought to regulate gene expression by organizing protein complexes through unclear mechanisms. XIST controls the inactivation of an entire X chromosome in female placental mammals. Here we develop and integrate several orthogonal structure-interaction methods to demonstrate that XIST RNA-protein complex folds into an evolutionarily conserved modular architecture. Chimeric RNAs and clustered protein binding in fRIP and eCLIP experiments align with long-range RNA secondary structure, revealing discrete XIST domains that interact with distinct sets of effector proteins. CRISPR-Cas9-mediated permutation of the Xist A-repeat location shows that A-repeat serves as a nucleation center for multiple Xist-associated proteins and m6A modification. Thus modular architecture plays an essential role, in addition to sequence motifs, in determining the specificity of RBP binding and m6A modification. Together, this work builds a comprehensive structure-function model for the XIST RNA-protein complex, and suggests a general strategy for mechanistic studies of large ribonucleoprotein assemblies.
Analysis of microbial compositions: a review of normalization and differential abundance analysis
Authors: Lin Huang , Peddada Shyamal Das 
Published: December 2020

AbstractIncreasingly, researchers are discovering associations between microbiome and a wide range of human diseases such as obesity, inflammatory bowel diseases, HIV, and so on. The first step towards microbiome wide association studies is the characterization of the composition of human microbiome under different conditions. Determination of differentially abundant microbes between two or more environments, known as differential abundance (DA) analysis, is a challenging and an important problem that has received considerable interest during the past decade. It is well documented in the literature that the observed microbiome data (OTU/SV table) are relative abundances with an excess of zeros. Since relative abundances sum to a constant, these data are necessarily compositional. In this article we review some recent methods for DA analysis and describe their strengths and weaknesses.