bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal Stromal Cell Delivery via an Ex Vivo Bioreactor Preclinical Test System Attenuates Clot Formation for Intravascular Application
Authors: O’Rourke Brian , Nguyen Sunny , Tilles Arno W. , Bynum James A. , Cap Andrew P , Parekkadan Biju , Barcia Rita N. 
Published: November 2020

AbstractWhile mesenchymal stromal cells (MSCs) are an appealing therapeutic option for a range of clinical applications, their potential to induce clotting when used systemically remains a safety concern, particularly in hypercoagulable conditions, such as in patients with severe COVID-19, trauma, or cancers. Here, we tested a novelex vivoapproach aimed at improving the safety of MSC systemic administration by use of a bioreactor. In this device, MSCs are seeded on the outside of a hollow-fiber filter, sequestering them behind a hemocompatible membrane, while still maintaining cross talk with blood cells and circulating signaling molecules. The potential for these bioreactor MSCs to induce clots in coagulable plasma was compared against “free” MSCs, as a model of systemic administration, which were directly injected into the circuit. Our results showed that physical isolation of the MSCs via a bioreactor extends the time necessary for clot formation to occur when compared to “free” MSCs. Measurement of cell surface data indicates the presence of known clot inducing factors, namely tissue factor and phosphatidylserine. Results also showed that recovering cells and flushing the bioreactor prior to use further prolonged clot formation time. Further, application of this technology in twoin vivomodels did not require additional heparin to maintain target ACT levels relative to the acellular device. Taken together, the use of hollow fiber filters to house MSCs, if adopted clinically, could offer a novel method to control systemic MSC exposure and prolong clot formation time.
Clinical positioning of the IAP antagonist tolinapant (ASTX660) in colorectal cancer
Authors: Crawford Nyree , Stott Katie , Sessler Tamas , McCann Christopher , McDaid William , Latimer Cheryl , Fox Jennifer , Munck Joanne M , Smyth Tomoko , Shah Alpesh , Martins Vanessa , Lawler Mark , Dunne Philip , Kerr Emma , McDade Simon S , Coyle Vicky , Longley Daniel B 
Published: November 2020

AbstractCancer cells frequently express elevated levels of Inhibitor of Apoptosis Proteins (IAPs): cIAPI, cIAP2 and XIAP. Elevated expression of cIAP1 and cIAP2 (but not XIAP) significantly correlated with poor prognosis in microsatellite stable (MSS) stage-III colorectal cancer (CRC) patients treated with adjuvant chemotherapy, suggesting their involvement in promoting resistance. Preclinical analysis of the IAP inhibitor tolinapant in CRC cell lines demonstrated robust on-target effects and caspase-8-dependent apoptosis that was inhibited by the caspase-8 paralogs FLIP and, unexpectedly, caspase-10. Importantly, tolinipant-induced apoptosis was augmented by standard-of-care chemotherapy (FOLFOX) in CRC disease models, due (at least in part) to FOLFOX-induced downregulation of Class-I histone deacetylases, leading to acetylation of the FLIP-binding partner Ku70 and downregulation of FLIP. Moreover, this effect could be phenocopied using a Class-I HDAC inhibitor. Further analyses revealed that caspase-8-knockout RIPK3-positive CRC models were sensitive to tolinostat-induced necroptosis, an effect that could be exploited with the FDA-approved caspase inhibitor emricasan. Our study provides evidence for immediate clinical exploration of tolinapant in combination with FOLFOX chemotherapy in poor prognosis MSS CRC with elevated cIAP1/2 expression.
Three-dimensional interrelationship between osteocyte network and forming mineral during human bone remodeling
Authors: Ayoubi Mahdi , van Tol Alexander F. , Weinkamer Richard , Roschger Paul , Brugger Peter C. , Berzlanovich Andrea , Bertinetti Luca , Roschger Andreas , Fratzl Peter 
Published: November 2020

AbstractDuring bone remodeling, osteoblasts are known to deposit unmineralized collagenous tissue (osteoid), which mineralizes after some time lag. Some of the osteoblasts differentiate into osteocytes, forming a cell network within the lacunocanalicular network (LCN) of bone. To get more insight into the potential role of osteocytes in the mineralization process of osteoid, sites of bone formation were three-dimensionally imaged in nine forming human osteons using focused ion beam-scanning electron microscopy (FIB-SEM). In agreement with previous observations, the mineral concentration was found to gradually increase from the central Haversian canal towards preexisting mineralized bone. Most interestingly, a similar feature was discovered on a length scale more than 100-times smaller, whereby mineral concentration increased from the LCN, leaving around the canaliculi a zone virtually free of mineral, the size of which decreases with progressing mineralization. This suggests that the LCN controls mineral formation but not just by diffusion of mineralization precursors, which would lead to a continuous decrease of mineral concentration from the LCN. Our observation is, however, compatible with the codiffusion and reaction of precursors and inhibitors from the LCN into the bone matrix.
Highly multiplexed spatially resolved gene expression profiling of mouse organogenesis
Authors: Lohoff T. , Ghazanfar S. , Missarova A. , Koulena N. , Pierson N. , Griffiths J.A. , Bardot E.S. , Eng C.-H.L. , Tyser R.C.V. , Argelaguet R. , Guibentif C. , Srinivas S. , Briscoe J. , Simons B.D. , Hadjantonakis A.-K. , Göttgens B. , Reik W. , Nichols J. , Cai L. , Marioni J.C. 
Published: November 2020

AbstractTranscriptional and epigenetic profiling of single-cells has advanced our knowledge of the molecular bases of gastrulation and early organogenesis. However, current approaches rely on dissociating cells from tissues, thereby losing the crucial spatial context that is necessary for understanding cell and tissue interactions during development. Here, we apply an image-based single-cell transcriptomics method, seqFISH, to simultaneously and precisely detect mRNA molecules for 387 selected target genes in 8-12 somite stage mouse embryo tissue sections. By integrating spatial context and highly multiplexed transcriptional measurements with two single-cell transcriptome atlases we accurately characterize cell types across the embryo and demonstrate how spatially-resolved expression of genes not profiled by seqFISH can be imputed. We use this high-resolution spatial map to characterize fundamental steps in the patterning of the midbrain-hindbrain boundary and the developing gut tube. Our spatial atlas uncovers axes of resolution that are not apparent from single-cell RNA sequencing data – for example, in the gut tube we observe early dorsal-ventral separation of esophageal and tracheal progenitor populations. In sum, by computationally integrating high-resolution spatially-resolved gene expression maps with single-cell genomics data, we provide a powerful new approach for studying how and when cell fate decisions are made during early mammalian development.
MetENP/MetENPWeb: An R package and web application for metabolomics enrichment and pathway analysis in Metabolomics Workbench
Authors: Choudhary Kumari Sonal , Fahy Eoin , Coakley Kevin , Sud Manish , Maurya Mano R , Subramaniam Shankar 
Published: November 2020

ABSTRACTWith the advent of high throughput mass spectrometric methods, metabolomics has emerged as an essential area of research in biomedicine with the potential to provide deep biological insights into normal and diseased functions in physiology. However, to achieve the potential offered by metabolomics measures, there is a need for biologist-friendly integrative analysis tools that can transform data into mechanisms that relate to phenotypes. Here, we describe MetENP, an R package, and a user-friendly web application deployed at the Metabolomics Workbench site extending the metabolomics enrichment analysis to include species-specific pathway analysis, pathway enrichment scores, gene-enzyme information, and enzymatic activities of the significantly altered metabolites. MetENP provides a highly customizable workflow through various user-specified options and includes support for all metabolite species with available KEGG pathways. MetENPweb is a web application for calculating metabolite and pathway enrichment analysis.Availability and ImplementationThe MetENP package is freely available from Metabolomics Workbench GitHub: (https://github.com/metabolomicsworkbench/MetENP), the web application, is freely available at (https://www.metabolomicsworkbench.org/data/analyze.php)
Accurate Genomic Variant Detection in Single Cells with Primary Template-Directed Amplification
Authors: Gonzalez Veronica , Natarajan Sivaraman , Xia Yuntao , Klein David , Carter Robert , Pang Yakun , Shaner Bridget , Annu Kavya , Putnam Daniel , Chen Wenan , Connelly Jon , Pruett-Miller Shondra , Chen Xiang , Easton John , Gawad Charles 
Published: November 2020

AbstractImprovements in whole genome amplification (WGA) would enable new types of basic and applied biomedical research, including studies of intratissue genetic diversity that require more accurate single-cell genotyping. Here we present primary template-directed amplification (PTA), a new isothermal WGA method that reproducibly captures >95% of the genomes of single cells in a more uniform and accurate manner than existing approaches, resulting in significantly improved variant calling sensitivity and precision. To illustrate the new types of studies that are enabled by PTA, we developed direct measurement of environmental mutagenicity (DMEM), a new tool for mapping genome-wide interactions of mutagens with single living human cells at base pair resolution. In addition, we utilized PTA for genome-wide off-target indel and structural variant detection in cells that had undergone CRISPR-mediated genome editing, establishing the feasibility for performing single-cell evaluations of biopsies from edited tissues. The improved precision and accuracy of variant detection with PTA overcomes the current limitations of accurate whole genome amplification, which is the major obstacle to studying genetic diversity and evolution at cellular resolution.
The role of advective transport mechanism in continental-scale transport of fungal plant epidemics
Authors: Elauria Nolan , Truong Taeah , Upadhyay Kush , Kogan Oleg 
Published: November 2020

AbstractIn examining the continental-scale plant pathogen spread, we focus on the competition between the short-range stochastic hopping within the atmospheric boundary layer, and the laminar advection by the currents in the free troposphere. The latter is typically ignored, since it is assumed that the population of spores which have reached the troposphere is small, and the fraction of the remaining spores that survived the subsequent journey is negligible due to ultraviolet light and frigid temperatures. However, we claim that it is in fact a crucial mechanism for continental-scale spread. We argue that free tropospheric currents can not be ignored, even as the probability for spores to reach them and to survive within them approaches zero. In other words, models that neglect tropospheric advection are fragile – their predictions change qualitatively if this alternative transport channel becomes accessible – even when the rate at which spores actually make use of this transport channel approaches zero.
BoxCarmax: a high-selectivity data-independent acquisition mass spectrometry method for the analysis of protein turnover and complex samples
Authors: Salovska Barbora , Li Wenxue , Di Yi , Liu Yansheng 
Published: November 2020

ABSTRACTThe data-independent acquisition (DIA) performed in the latest high-resolution, high-speed mass spectrometers offers a powerful analytical tool for biological investigations. The DIA mass spectrometry (MS) combined with the isotopic labeling approach holds a particular promise for increasing the multiplexity of DIA-MS analysis, which could assist the relative protein quantification and the proteome-wide turnover profiling. However, the wide isolation windows employed in conventional DIA methods lead to a limited efficiency in identifying and quantifying isotope-labelled peptide pairs. Here, we optimized a high-selectivity DIA-MS namedBoxCarmaxthat supports the analysis of complex samples, such as those generated from Stable isotope labeling by amino acids in cell culture (SILAC) and pulse SILAC (pSILAC) experiments.BoxCarmaxenables multiplexed acquisition at both MS1- and MS2-levels, through the integration of BoxCar and MSX features, as well as a gas-phase separation strategy. We found BoxCarmax modestly increased the identification rate for label-free and labeled samples but significantly improved the quantitative accuracy in SILAC and pSILAC samples. We further applied BoxCarmax in studying the protein degradation regulation during serum starvation stress in cultured cells, revealing valuable biological insights. Our study offered an alternative and accurate approach for the MS analysis of protein turnover and complex samples.
A coarse-grained NADH redox model enables inference of subcellular metabolic fluxes from fluorescence lifetime imaging
Authors: Yang Xingbo , Ha Gloria , Needleman Daniel J. 
Published: November 2020

AbstractMitochondrial metabolism is of central importance to diverse aspects of cell and developmental biology. Defects in mitochondria are associated with many diseases, including cancer, neuropathology, and infertility. Our understanding of mitochondrial metabolismin situand dysfunction in diseases are limited by the lack of techniques to measure mitochondrial metabolic fluxes with sufficient spatiotemporal resolution. Herein, we developed a new method to infer mitochondrial metabolic fluxes in living cells with subcellular resolution from fluorescence lifetime imaging of NADH. This result is based on the use of a generic coarse-grained NADH redox model. We tested the model in mouse oocytes and human tissue culture cells subject to a wide variety of perturbations by comparing predicted fluxes through the electron transport chain (ETC) to direct measurements of oxygen consumption rate. Interpreting the FLIM measurements of NADH using this model, we discovered a homeostasis of ETC flux in mouse oocytes: perturbations of nutrient supply and energy demand do not change ETC flux despite significantly impacting NADH metabolic state. Furthermore, we observed a subcellular spatial gradient of ETC flux in mouse oocytes and found that this gradient is primarily a result of heterogeneous mitochondrial proton leak. We concluded from these observations that ETC flux in mouse oocytes is not controlled by energy demand or supply, but by the intrinsic rates of mitochondrial respiration.
Integrative/ distributive negotiations in Latin America: latent class analysis
Authors: Ogliastri Enrique , Ickis John , Casó Ramiro 
Published: November 2020

PurposeThe purpose of this study is to test the universality of the behavioral theory of negotiation developed in the United States, particularly the integrative/distributive models, and to find negotiators' prototypes in international negotiations conducted in a Latin American country.Design/methodology/approachAn open questionnaire was administered to a convenience sample of 104 resident foreigners (expatriates) who reported the negotiation patterns of Costa Ricans. The qualitative data were coded in 52 variables (inte-rater reliability Fleiss' KappaK= 0.65). A total of ten variables were selected to measure distributive/integrative patterns of negotiations. Latent class analysis (LCA) uncovered the latent structure of negotiations.Findings(1) The distributive (70% found in the sample) and integrative (30%) negotiation models hold in this culture. (2) The incorporation of handling emotions and interpersonal orientation in the integrative model seem to be an important theoretical and practical trend.Research limitations/implications(1) A larger sample size is needed to compare with data from other countries of the region and the world. (2) The use of emotions and interpersonal orientation in the integrative negotiation paradigm require further investigation. As practical implications, detailed negotiation advice is offered to Costa Ricans as well as to expatriates working there.Originality/valueTo identify negotiation patterns in an understudied region of the world, the distributive/integrative models of the behavioral theory of negotiations are a key focus with which to extend the literature. There are important elements of culture within the negotiation patterns, in line with trends of an evolving paradigm of integrative crosscultural negotiations.
The emergence and evolution of reliability theory for water distribution networks
Authors: Zarghami Seyed Ashkan , Gunawan Indra 
Published: November 2020

PurposeAs a response to the growing operational and disruptive threats to water distribution networks (WDNs), researchers have developed a vast array of methods for the reliability analysis of WDNs. In order to follow this growing number of methods, this paper reviews and documents in one place the historical developments in the reliability analysis of WDN.Design/methodology/approachA systematic literature review (SLR) is carried out to summarize the state-of-the-art research on reliability analysis of WDNs. In conducting this systemic literature review, the authors adopted an iterative approach to define appropriate keywords, analyze and synthesize data and finalizing the classification results.FindingsFirst, the hydraulic approach to reliability analysis is currently pervasive, and relatively little academic research has addressed the topological reliability analysis of WDNs. Second, in order to provide a comprehensive picture of the network reliability, a different approach that integrates topological and hydraulic attributes seems a more effective method. Third, the conventional reliability analysis methods are only effective for demonstrating a snapshot of these networks at a given point in time. The availability of methods that enable researchers to evaluate the reliability in response to changes in its variables is still a major challenge.Originality/valueThe present paper facilitates future research in the reliability analysis of WDNs by providing a source of references for researchers and water utilities. Further, this article makes a contribution to the literature by offering a roadmap for future reliability analysis of WDNs by reviewing the evolution of the current reliability analysis methods throughout history.
Under construction: action research in innovation measurement
Authors: Svensson de Jong Ilse 
Published: November 2020

PurposeThis paper has chosen a participatory action design (PAD) to approach the construction of KPIs in a novel way. A PAD will assist the researcher to encourage involvement, engagement of multiple stakeholders in the KPIs construction process.Design/methodology/approachA workshop series based on participatory action design was developed together with the researcher and stakeholders at the innovation department of a large international organization. PAD facilitated interaction between the researcher, stakeholders, and KPIs under construction.FindingsThe findings show that the PAD workshops created interlevel collaboration and group dynamics in constructing the KPI. The knowledge that was shared during the PAD workshops enabled an understanding of the process of constructing a KPI in innovation, where stakeholders design and implement simultaneously. In the end, it was a challenge to construct a KPI using the PAD, as certain conditions seemed not to be.Research limitations/implicationsThis paper enhances our empirical understanding of applying PAD to construct KPIs in innovation. This study adds to the growing interest in literature to implement novel methods such as PAD to construct a KPI in innovation.Practical implicationsPractically, the findings of this study will inform managers in innovation (projects) to use a method such as PAD to construct KPIs in innovation. This study shows the implication of using a PAD for a KPI and what opportunities and challenges it can bring.Originality/valueThis paper is one of the few papers that address using the participatory action design methodology for the construction of KPIs in innovation. To date, PAD is rarely used to construct KPIs in innovation.
Monetary policy shock and industrial production: industry-level evidence from the US
Authors: Ahmad Nazneen , Rangaraju Sandeep Kumar 
Published: November 2020

PurposeThis paper investigates the impact of a monetary policy shock on the production of a sample of 312 industries in manufacturing, mining and utilities in the United States using a factor-augmented vector autoregression (FAVAR) model.Design/methodology/approachThe authors use a FAVAR model that builds on Bernanke et al. (2005) and Boivin et al. (2009). The main assumption in this model is that the dynamics of a large set of macro variables are captured by some observed and unobserved common factors. The unobserved factors are extracted from a large set of macroeconomic data. The key advantage of using this model is that it allows extracting the impulse responses of a wide range of macroeconomic variables to structural shocks in the federal funds rate.FindingsThe results indicate that industries exhibit differential responses to an unanticipated monetary policy tightening. In general, manufacturing industries appear to be more sensitive compared to mining, and utility industries and durable manufacturing industries are found to be more sensitive than those within nondurable and other manufacturing industries to a monetary policy shock. While all industries respond to the policy shock, most of the responses are reversed between 12 and 22 months.Research limitations/implicationsThe implication of our results is that monetary policy can be used to impact most US industries for four years and beyond. The existence of disparate responses across industries underscores the difficulty of implementing a monetary policy that will generate the same impact across industries. As the effects of the policy are distinct, policymakers may want to attend to the unique impacts and implement industry-specific policy.Practical implicationsThe study is important in the context of the current challenges in the US economy caused by the spread of coronavirus. For example, to tackle the current pandemic, the researchers are trying to come up with cures for COVID-19. A considerable response of the chemical industry that provides materials to pharmaceutical and medicine manufacturing to the monetary policy shock implies that an expansionary monetary policy may facilitate an invention and adequate supply of the cure later on. The same policy may not effectively stimulate production in apparel or leather product industries that are being hard hit by the pandemic.Originality/valueThe study contributes to the literature in broadly two aspects. First, to the best of our knowledge, this is the first paper that investigates the impact of a monetary policy shock on a sample of 312 industries in manufacturing, mining and utilities in the US. Second, to identify structural shocks and investigate the effects of monetary policy shocks on economic activity, the authors diverge from the literature's traditional approach, i.e. the vector autoregression (VAR) method and use a FAVAR method. The FAVAR provides a comprehensive description of the impact of a monetary policy innovation on different industries.