bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding mAb aggregation during low pH viral inactivation and subsequent neutralization
Authors: Wälchli Ruben , Ressurreição Mariana , Vogg Sebastian , Feidl Fabian , Angelo James , Xu Xuankuo , Ghose Sanchayita , Jian Li Zheng , Le Saoût Xavier , Souquet Jonathan , Broly Hervé , Morbidelli Massimo 
Published: December 2019

AbstractMonoclonal antibodies (mAbs) and related recombinant proteins continue to gain importance in the treatment of a great variety of diseases. Despite significant advances, their manufacturing can still present challenges owing to their molecular complexity and stringent regulations with respect to product purity, stability, safety, and so forth. In this context, protein aggregates are of particular concern due to their immunogenic potential. During manufacturing, mAbs routinely undergo acidic treatment to inactivate viral contamination, which can lead to their aggregation and thereby to product loss. To better understand the underlying mechanism so as to propose strategies to mitigate the issue, we systematically investigated the denaturation and aggregation of two mAbs at low pH as well as after neutralization. We observed that at low pH and low ionic strength, mAb surface hydrophobicity increased whereas molecular size remained constant. After neutralization of acidic mAb solutions, the fraction of monomeric mAb started to decrease accompanied by an increase on average mAb size. This indicates that electrostatic repulsion prevents denatured mAb molecules from aggregation under acidic pH and low ionic strength, whereas neutralization reduces this repulsion and coagulation initiates. Limiting denaturation at low pH by d‐sorbitol addition or temperature reduction effectively improved monomer recovery after neutralization. Our findings might be used to develop innovative viral inactivation procedures during mAb manufacturing that result in higher product yields.
Computational fluid dynamic analysis of bioprinted self‐supporting perfused tissue models
Authors: Sego T. J. , Prideaux Matthew , Sterner Jane , McCarthy Brian Paul , Li Ping , Bonewald Lynda F. , Ekser Burcin , Tovar Andres , Jeshua Smith Lester 
Published: December 2019

AbstractNatural tissues are incorporated with vasculature, which is further integrated with a cardiovascular system responsible for driving perfusion of nutrient‐rich oxygenated blood through the vasculature to support cell metabolism within most cell‐dense tissues. Since scaffold‐free biofabricated tissues being developed into clinical implants, research models, and pharmaceutical testing platforms should similarly exhibit perfused tissue‐like structures, we generated a generalizable biofabrication method resulting in self‐supporting perfused (SSuPer) tissue constructs incorporated with perfusible microchannels and integrated with the modular FABRICA perfusion bioreactor. As proof of concept, we perfused an MLO‐A5 osteoblast‐based SSuPer tissue in the FABRICA. Although our resulting SSuPer tissue replicated vascularization and perfusion observed in situ, supported its own weight, and stained positively for mineral using Von Kossa staining, our in vitro results indicated that computational fluid dynamics (CFD) should be used to drive future construct design and flow application before further tissue biofabrication and perfusion. We built a CFD model of the SSuPer tissue integrated in the FABRICA and analyzed flow characteristics (net force, pressure distribution, shear stress, and oxygen distribution) through five SSuPer tissue microchannel patterns in two flow directions and at increasing flow rates. Important flow parameters include flow direction, fully developed flow, and tissue microchannel diameters matched and aligned with bioreactor flow channels. We observed that the SSuPer tissue platform is capable of providing direct perfusion to tissue constructs and proper culture conditions (oxygenation, with controllable shear and flow rates), indicating that our approach can be used to biofabricate tissue representing primary tissues and that we can model the system in silico.
Construction of hypervesiculation Escherichia coli strains and application for secretory protein production
Authors: Ojima Yoshihiro , Sawabe Tomomi , Konami Katsuya , Azuma Masayuki 
Published: December 2019

AbstractOuter membrane vesicles (OMVs) are extracellular vesicles released from the surface of Gram‐negative bacteria, including Escherichia coli. Several gene‐deficient mutants relating to envelope stress (nlpI and degP) and phospholipid accumulation in the outer leaflet of the outer membrane (mlaA and mlaE) increase OMV production. This study examined the combinatorial deletion of these genes in E. coli and its effect on OMV production. The nlpI and mlaE double‐gene‐knockout mutant (ΔmlaEΔnlpI) showed the highest OMV production. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis‐based quantitative analysis showed that OMV production by strain ΔmlaEΔnlpI was ~30 times that by the wild‐type (WT). In addition, to evaluate the protein secretion capacity of OMVs, a green fluorescent protein (GFP) fused with outer membrane protein W (OmpW) was expressed in OMVs. Western blot analysis showed that GFP secretion through OMVs reached 3.3 mg/L in the culture medium of strain ΔmlaEΔnlpI/gfp, 500 times that for the WT. Our approach using OMVs for extracellular protein secretion in E. coli is an entirely new concept compared with existing secretion systems.
When companies improve the sustainability of the natural environment: A study of large U.S. companies
Authors: De Mendonca Taryn , Zhou Yan 
Published: December 2019

AbstractIn light of the call for companies to abandon current approaches to environmental management, this study adds to the environmental strategy literature and uses the evidence of competitive dynamics among companies to identify a mechanism by which companies invest in proactive environmental strategies and thereby improve the sustainability of the natural environment. An examination utilizing fixed effects regressions on a sample of large U.S.‐based companies reveal that even after controlling the number, environmental and financial performance of leading (environmental) companies, laggard (environmental) companies are more likely to invest in proactive environmental strategies when their leading peers display higher sustainability orientations. Neither the expectation of government regulation nor social movement pressure was found to be influential in this relationship. Therefore, the future dominance of companies' investments in the sustainability of the natural environment will be driven by companies themselves as long as competitive advantages are expected.
Origin of Regio‐ and Stereoselectivity in the NHC‐catalyzed Reaction of Alkyl Pyridinium with Aliphatic Enal
Authors: Wang Yang , Qu Ling‐Bo , Lan Yu , Wei Donghui 
Published: December 2019

AbstractThe mechanisms of N‐heterocyclic carbene (NHC)‐catalyzed dearomatization reaction of alkyl pyridinium have been intensively studied using the density functional theory (DFT) method. The chemoselectivity and stereoselectivity were both analyzed based on the established mechanisms. The computational results showed that the chemoselective C4‐addition occurred before the C2‐addition, which is mainly because the C4 atom was more reactive according to the local reactivity analysis. The stereoselectivity was also investigated, and the C−C bond formation step was identified as the stereoselectivity‐determining step. The C−H⋅⋅⋅F and O−H⋅⋅⋅N interactions are identified as the main factors that govern the stereoselectivity by NCI analysis, and the preferred product was the RS‐configuration. This theoretical investigation would provide a case for understanding and predicting the selectivity of the organocatalytic dearomatization reactions of alkyl pyridinium.
Activation of α‐Fe2O3 for Photoelectrochemical Water Splitting Strongly Enhanced by Low Temperature Annealing in Low Oxygen Containing Ambient
Authors: Makimizu Yoichi , Nguyen Nhat Truong , Tucek Jiri , Ahn Hyo‐Jin , Yoo JeongEun , Poornajar Mahshid , Hwang Imgon , Kment Stepan , Schmuki Patrik 
Published: December 2019

AbstractPhotoelectrochemical (PEC) water splitting is a promising method for the conversion of solar energy into chemical energy stored in the form of hydrogen. Nanostructured hematite (α‐Fe2O3) is one of the most attractive materials for a highly efficient charge carrier generation and collection due to its large specific surface area and the short minority carrier diffusion length. In the present work, the PEC water splitting performance of nanostructured α‐Fe2O3 is investigated which was prepared by anodization followed by annealing in a low oxygen ambient (0.03 % O2 in Ar). It was found that low oxygen annealing can activate a significant PEC response of α‐Fe2O3 even at a low temperature of 400 °C and provide an excellent PEC performance compared with classic air annealing. The photocurrent of the α‐Fe2O3 annealed in the low oxygen at 1.5 V vs. RHE results as 0.5 mA cm−2, being 20 times higher than that of annealing in air. The obtained results show that the α‐Fe2O3 annealed in low oxygen contains beneficial defects and promotes the transport of holes; it can be attributed to the improvement of conductivity due to the introduction of suitable oxygen vacancies in the α‐Fe2O3. Additionally, we demonstrate the photocurrent of α‐Fe2O3 annealed in low oxygen ambient can be further enhanced by Zn‐Co LDH, which is a co‐catalyst of oxygen evolution reaction. This indicates low oxygen annealing generates a promising method to obtain an excellent PEC water splitting performance from α‐Fe2O3 photoanodes.
Kinetische Parameteridentifikation und Modelldiskriminierung am Beispiel der nassen Oxidation von Thiosulfat
Authors: Holz Stephan , Stewers Lennart , Thielert Holger , Guetta Zion , Repke Jens‐Uwe 
Published: December 2019

AbstractIn der Kokereitechnik fallen belastete Abwässer an, die effizient behandelt werden müssen, um die Umwelt nicht zu belasten und den gesetzlichen Verordnungen gerecht zu werden. Hierzu ist ein genaues Prozessverständnis notwendig. Aufgrund der Vielzahl an möglichen Modifikationen nehmen Schwefelverbindungen eine Sonderstellung ein, weswegen die Kenntnis der verschiedenen Reaktionspfade und ‐kinetiken für die Auslegung der Apparate essenziell ist. Mittels Parameterschätzung und Modeldiskriminierung werden in diesem Beitrag Kinetiken anhand von Experimentaldaten ermittelt und Reaktionsschemata der Nassoxidation von Thiosulfat bewertet, um den Konzentrationsverlauf aller Spezies hinreichend genau beschreiben zu können.
Analysing the use of tools, initiatives, and approaches to promote sustainability in corporations
Authors: Lozano Rodrigo 
Published: December 2019

AbstractInterest in sustainability from the corporate sector is evidenced by over 13,000 companies in 160 countries that have signed the United Nations Global Compact. In this context, a number of tools, initiatives, and approaches (TIAs), e.g., circular economy, corporate social responsibility, eco‐efficiency, life cycle assessment, and sustainability reporting have been developed by and for corporations to engage and promote sustainability within their systems. Each of the TIAs has advantages when addressing sustainability issues and the company system's elements, but it has disadvantages in dealing with their complexities and interactions. Relying only on one TIA results in a limited contribution to sustainability, whereas using too many TIAs wastes resources and energy. The Corporate and Industrial Voluntary Initiatives for Sustainability (CIVIS) has been proposed to better combine the TIAs. A survey was developed to investigate the use of 24 TIAs. The survey was sent to a database of 5,299 organisations (of which 3,603 were companies), from which 202 responses were obtained. The responses were analysed using ratio analysis, principal component analysis, and cluster analysis. The responses show that some TIAs are well known and provide good results when used, for example, corporate social responsibility, corporate sustainability, and Global Reporting Initiative reports. The analyses show a number of groups of the TIAs that can help to better combine them. The paper updates the CIVIS framework in order to provide clearer guidance on how to combine the TIAs. A combination of between four and six initiatives appears to be most effective way to promote sustainability. The TIAs can help to promote sustainability in corporations, but they need to be combined correctly in order to address holistically the four dimensions of sustainability, the system elements, and stakeholders, while avoiding duplication of tasks and wasting resources.
EUS‐FNA diagnosis of pancreatic serous cystadenoma with the aid of cell blocks and α‐inhibin immunochemistry: A case series
Authors: Sydney Guy I. , Ioakim Kalliopi J. , Michaelides Constantinos , Sepsa Athanasia , Sopaki‐Valalaki Anastasia , Tsiotos Gregory G. , Theocharis Stamatios , Salla Charitini , Nikas Ilias 
Published: December 2019

AbstractSerous cystadenoma (SCA) is an uncommon benign pancreatic neoplasm that is most often managed conservatively with follow‐up rather than surgical excision. Therefore, to avoid the serious complications of pancreatic surgery, SCA should be diagnosed accurately at the preoperative level. Preoperative SCA diagnosis requires a multimodal diagnostic approach that includes imaging, cystic fluid biochemical analysis and/or endoscopic ultrasound fine‐needle aspiration (EUS‐FNA). In this brief report, we describe six EUS‐FNA cases from five patients that were reported as “benign, consistent with serous cystadenoma”. Samples were hypocellular, composed of loose clusters and single cuboidal, bland‐looking cells among epithelial sheets representing gastrointestinal contamination. Cell blocks were prepared and all six FNA cases revealed cuboidal cells with a positive α‐inhibin immunophenotype, consistent with a diagnosis of SCA. As EUS‐FNAs of SCA commonly result in non‐diagnostic interpretations, cell block preparations with subsequent immunochemistry can increase their diagnostic accuracy and guide patient management.
Potential effects of climate change on NRCS Wetland Restoration Easements: An ecohydrological assessment
Authors: Cassatt Molly Stetz , Wilcox Douglas A. 
Published: December 2019

AbstractWater cycles are expected to change globally with predicted climate warming. Yet predicted shifts in hydrological regimes are rarely incorporated into wetland restoration planning, despite large investments in projects very susceptible to hydrological changes. We assessed potential effects of climate change on previously restored wetlands to identify siting and design issues for use in guiding adaptive management or planning future restoration projects. Five United States Department of Agriculture Natural Resources Conservation Service Wetland Reserve Easements in Genesee County, New York, were studied from 2013 through 2014. Elevations of surface water and groundwater were monitored, piezometric measurements made, and water chemistry and plant community data collected. Precipitation, surface water, and groundwater hydrologic data were used to relate each restored wetland to vulnerability of climate change. Although all five sites were functioning as planned, three sites had less vulnerability to climate change due to their connection to more stable sources of groundwater, position within the hydrological landscape, or design features that mimic the natural landscape. Suggestions for adaptive management on already implemented projects include actively managing water‐control structures, enhancing microtopography, and increasing plant diversity by planting or seeding. Potential sites for future restoration projects should be ranked based on location in the watershed, presence of hydric soils, past and potential hydrological connections, and sustainability of hydrology, especially groundwater sourcing. Design options should attempt to mimic natural landscape features, refrain from overengineering, and allow for flexible management of hydroperiods.
Comparative study of the fire protection performance and thermal stability of intumescent fire‐retardant coatings filled with three types of clay nano‐fillers
Authors: Xu Zhisheng , Zhou Huan , Yan Long , Jia Hongyu 
Published: December 2019

SummaryThe fire protection and thermal stability properties of intumescent fire‐retardant coatings filled with three various clay nano‐fillers (layer double hydroxide [LDH], montmorillonite [MMT], and sepiolite) were compared by fire protection tests and thermo‐gravimetric analysis. The fire protection tests show that the incorporation of three fillers improves the fire protection properties of the intumescent fire‐retardant coatings and the addition of 1 wt% sepiolite exhibits the lowest flame spread rating of 9.9 and equilibrium backside temperature of 164.5°C at 900 seconds. TG analysis shows that the incorporation of nano‐fillers imparts a considerable enhancement of thermal stability and char formation to the intumescent coatings. Especially, the coating with 1 wt% sepiolite acquires the highest residual weight of 34.2% among the samples. Char residue analysis presents that the introduction of clay nano‐fillers plays a positive role in enhancing the compactness and anti‐oxidation ability of the char residues, and this positive effect as well as the flame‐retardant efficiency depends on the types of clay nano‐fillers. The three types of layered clay nano‐fillers exhibit synergistic flame‐retardant effectiveness in the order of sepiolite > MMT > LDH.
Longitudinal brain atrophy distribution in advanced Parkinson's disease: What makes the difference in “cognitive status” converters?
Authors: Gorges Martin , Kunz Martin S. , Müller Hans‐Peter , Liepelt‐Scarfone Inga , Storch Alexander , Dodel Richard , Hilker‐Roggendorf Rüdiger ,   LANDSCAPE Consortium, Berg Daniela , Kalbe Elke , Braak Heiko , Del Tredici Kelly , Baudrexel Simon , Huppertz Hans‐Jürgen , Kassubek Jan 
Published: December 2019

AbstractWe investigated the brain atrophy distribution pattern and rate of regional atrophy change in Parkinson's disease (PD) in association with the cognitive status to identify the morphological characteristics of conversion to mild cognitive impairment (MCI) and dementia (PDD). T1‐weighted longitudinal 3T MRI data (up to four follow‐up assessments) from neuropsychologically well‐characterized advanced PD patients (n = 172, 8.9 years disease duration) and healthy elderly controls (n = 85) enrolled in the LANDSCAPE study were longitudinally analyzed using a linear mixed effect model and atlas‐based volumetry and cortical thickness measures. At baseline, PD patients presented with cerebral atrophy and cortical thinning including striatum, temporoparietal regions, and primary/premotor cortex. The atrophy was already observed in “cognitively normal” PD patients (PD‐N) and was considerably more pronounced in cognitively impaired PD patients. Linear mixed effect modeling revealed almost similar rates of atrophy change in PD and controls. The group comparison at baseline between those PD‐N whose cognitive performance remained stable (n = 42) and those PD‐N patients who converted to MCI/PDD (“converter” cPD‐N, n = 26) indicated suggested cortical thinning in the anterior cingulate cortex in cPD‐N patients which was correlated with cognitive performance. Our results suggest that cortical brain atrophy has been already expanded in advanced PD patients without overt cognitive deficits while atrophy progression in late disease did not differ from “normal” aging regardless of the cognitive status. It appears that cortical atrophy begins early and progresses already in the initial disease stages emphasizing the need for therapeutic interventions already at disease onset.
Long‐term opioid use in curative‐intent radiotherapy: One‐Year outcomes in head/neck cancer patients
Authors: Schumacher Leif‐Erik D. , Sargi Zoukaa B. , Masforroll Melissa , Kwon Deukwoo , Zhao Wei , Rueda‐Lara Maria A. , Freedman Laura M. , Elsayyad Nagy , Samuels Stuart E. , Abramowitz Matthew C. , Samuels Michael A. 
Published: December 2019

AbstractBackgroundNo study has determined the incidence of long‐term opioid use, or risk factors for long‐term use, ≥1 year after radiotherapy.MethodsMedical records of 276 head/neck cancer patients were retrospectively assessed for persistent opioid use 1‐year after curative‐intent radiotherapy. Numerous potential risk factors were assessed and the physicians' documented reasons for continued use were qualitatively categorized as suspected opioid use disorder (OUD) or as medically indicated for control of ongoing pain.ResultsOf note, 20 of 276 patients continued using opioids long‐term. High maximum opioid dose and the use of opioids and/or psychotropics/non‐opioid analgesics at the radiation oncology intake visit were associated with this outcome. Three patients continued due to suspected OUD and 17 due to medical indications.ConclusionOf note, 7.2% of patients developed long‐term opioid use, which was associated with high maximum opioid dose and early initiation of opioids and/or psychotropics/non‐opioid analgesics. Physicians cited medical indications as the primary reason for continued use.
Insights From Liver‐Humanized Mice on Cholesterol Lipoprotein Metabolism and LXR‐Agonist Pharmacodynamics in Humans
Authors: Minniti Mirko E. , Pedrelli Matteo , Vedin Lise‐Lotte , Delbès Anne‐Sophie , Denis Raphaël G.P. , Öörni Katariina , Sala Claudia , Pirazzini Chiara , Thiagarajan Divya , Nurmi Harri J. , Grompe Markus , Mills Kevin , Garagnani Paolo , Ellis Ewa C.S. , Strom Stephen C. , Luquet Serge H. , Wilson Elizabeth M. , Bial John , Steffensen Knut R. , Parini Paolo 
Published: December 2019

Background and Aims
Genetically modified mice have been used extensively to study human disease. However, the data gained are not always translatable to humans because of major species differences. Liver‐humanized mice (LHM) are considered a promising model to study human hepatic and systemic metabolism. Therefore, we aimed to further explore their lipoprotein metabolism and to characterize key hepatic species‐related, physiological differences.

Approach and Results

Fah−/−
, Rag2−/−
, and Il2rg−/−
knockout mice on the nonobese diabetic (FRGN) background were repopulated with primary human hepatocytes from different donors. Cholesterol lipoprotein profiles of LHM showed a human‐like pattern, characterized by a high ratio of low‐density lipoprotein to high‐density lipoprotein, and dependency on the human donor. This pattern was determined by a higher level of apolipoprotein B100 in circulation, as a result of lower hepatic mRNA editing and low‐density lipoprotein receptor expression, and higher levels of circulating proprotein convertase subtilisin/kexin type 9. As a consequence, LHM lipoproteins bind to human aortic proteoglycans in a pattern similar to human lipoproteins. Unexpectedly, cholesteryl ester transfer protein was not required to determine the human‐like cholesterol lipoprotein profile. Moreover, LHM treated with GW3965 mimicked the negative lipid outcomes of the first human trial of liver X receptor stimulation (i.e., a dramatic increase of cholesterol and triglycerides in circulation). Innovatively, LHM allowed the characterization of these effects at a molecular level.

Conclusions
LHM represent an interesting translatable model of human hepatic and lipoprotein metabolism. Because several metabolic parameters displayed donor dependency, LHM may also be used in studies for personalized medicine.