bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coping with coopetition—Facing dilemmas in cooperation for sustainable development: The case of the Dutch smart grid industry
Authors: Planko Julia , Chappin Maryse M.H. , Cramer Jacqueline , Hekkert Marko P. 
Published: January 2019

AbstractThis paper is amongst the first to examine coopetition strategy for sustainable development at the network level. Companies who want to successfully implement complex innovative technologies that support sustainable development need to collaborate with other actors of the innovation ecosystem, including their competitors, so that they can develop standards, interoperable products, pool knowledge, and resources and bundle forces to compete against other technologies. Collaboration with competitors brings benefits, but also many risks. We investigated how firms cope with these risks when establishing an innovation ecosystem to implement a new technology in society. We conducted research in the Dutch smart grids sector and explored how these firms minimize inherent risks of coopetition. We found that system‐building actors in the Dutch smart grid field not only minimize inherent risks, but from the start of their collaboration they implement so‐called enablers to prevent these risks upfront.
The identity of Brexit: A cultural psychology analysis
Authors: Veltri Giuseppe A. , Redd Rozlyn , Mannarini Terri , Salvatore Sergio 
Published: January 2019

AbstractIn this paper, we propose a culturalist interpretation of the outcome of the Brexit referendum. This interpretation is grounded on the analysis of the U.K.'s cultural milieu, which is part of a more general study of the cultural milieus of several European countries. Specific to the United Kingdom, our analysis is based on a questionnaire carried out on a representative sample of U.K. respondents stratified by sociodemographic variables and geographic region (NUTS1). Responses to the questionnaire were subjected to multidimensional analysis—a combination of multiple correspondence analysis and cluster analysis.Findings about the multicountry analysis show how cultural milieus are characterized by five basic, embodied, affect‐laden, generalized worldviews (defined as “Symbolic Universes”). Four out of five symbolic universes consist of a way of interpreting reality by a specific anchorage (i.e., the ethical norm, the institutional order, the emotional experience interpersonal bond, and the belongingness). One symbolic universe can be viewed as the anomic reaction to the failure of those anchorages. Focusing on Brexit, by means of a discriminant analysis, it is showed how the incidence of the symbolic universes (and of the underpinning basic dimensions of meaning within the 12 U.K. macroregions') enables to identify differentially the macroregions with high proportion of “leave” at the Brexit referendum against those with low proportion. More specifically, the high “leave” macroregion are characterized by higher relevance of cultural forms anchored on local identity/belongingness. Findings are discussed within the wider aims of the project and its implications for a cultural psychology informed policymaking.
Synthesis and Application of Methyl N,O‐Hydroxylamine Muramyl Peptides
Authors: Lazor Klare M. , Zhou Junhui , DeMeester Kristen E. , D'Ambrosio Elizabeth A. , Grimes Catherine L. 
Published: January 2019

AbstractThe innate immune system's interaction with bacterial cells plays a pivotal role in a variety of human diseases. Carbohydrate units derived from a component of bacterial cell wall, peptidoglycan (PG), are known to stimulate an immune response. Nonetheless, access to modified late‐stage peptidoglycan intermediates is limited due to their synthetic complexity. A method to rapidly functionalize PG fragments is needed to better understand the natural host–PG interactions. Here methyl N,O‐hydroxylamine linkers are incorporated onto a synthetic PG derivative, muramyl dipeptide (MDP). The modification of MDP maintained the ability to stimulate a nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) immune response dependent on the expression of nucleotide‐binding oligomerization domain‐containing protein 2 (Nod2). Intrigued by this modification's maintenance of biological activity, several applications were explored. Methyl N,O‐hydroxylamine MDP was amendable to N‐hydroxylsuccinimide (NHS) chemistry for bioconjugation to fluorophores as well as a self‐assembled monolayer for Nod2 surface plasmon resonance analysis. Finally, linker incorporation was applicable to larger PG fragments, both enzymatically generated from Escherichia coli or chemically synthesized. This methodology provides rapid access to PG probes in one step and allows for the installation of a variety of chemical handles to advance the molecular understanding of PG and the innate immune system.
Silencing of MEG3 inhibited ox‐LDL‐induced inflammation and apoptosis in macrophages via modulation of the MEG3/miR‐204/CDKN2A regulatory axis
Authors: Yan Long , Liu Zhanchuan , Yin Haoyuan , Guo Zhenjie , Luo Qi 
Published: January 2019

AbstractAtherosclerosis (AS) is one of the most common chronic inflammatory diseases and a major cause of morbidity and mortality. However, the underlying molecular mechanisms of the progression of AS are still largely unknown. Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) play important roles in a variety of biological processes and the physiological and pathological progression of human diseases. In this study, we aimed to explore the role and underlying molecular mechanism of lncRNA MEG3 in Raw264.7 cells treated with oxidized low‐density lipoprotein (ox‐LDL). First, we found that ox‐LDL inhibited the cell viability and proliferation, increased TNFα and IL1β secretion and induced the apoptosis of Raw264.7 cells. Second, we demonstrated that ox‐LDL upregulated MEG3 expression and that knockdown of MEG3 inhibited the action of ox‐LDL in Raw264.7 cells. Third, we showed that MEG3 sponged miR‐204 in Raw264.7 cells treated with ox‐LDL. Fourth, we demonstrated that miR‐204 regulated the expression of cyclin‐dependent kinase inhibitor 2A (CDKN2A) in Raw264.7 cells treated with ox‐LDL. Finally, we revealed that MEG3 exerted its function via the regulation of the MEG3/miR‐204/CDKN2A regulatory axis in Raw264.7 cells treated with ox‐LDL. In summary, our study identified the role of the MEG3/miR‐204/CDKN2A pathway in Raw264.7 cells treated with ox‐LDL, revealed a novel regulatory pathway in AS and indicated potential novel characteristic biomarkers and therapeutic targets for AS.
Functional prediction and characterization of Dip2 gene in mice
Authors: Ma Jun , Chen Li , He Xiao‐Xiao , Wang Ya‐Jun , Yu Hua‐Li , He Zi‐Xuan , Zhang Lu‐Qing , Zheng Yao‐Wu , Zhu Xiao‐Juan 
Published: January 2019

AbstractDisconnected interacting protein 2 (DIP2) is a highly conserved protein family among invertebrates and vertebrates, but its function remains unclear. In this paper, we summarized the conservation of gene sequences and protein domains of DIP2 family members and predicted that they may have a similar functional role in acetyl‐coenzyme A (acetyl‐CoA) synthesis. We then used the most characterized member, disconnected interacting protein 2 homolog A (DIP2A), for further study. DIP2A is a cytoplasmic protein that is preferentially localized to mitochondria, and its acetyl‐CoA synthetase activity has been demonstrated in vitro. Furthermore, the level of acetyl‐CoA in HEK293 cells overexpressing DIP2A was increased, which is consistent with its metabolically related function. Together, these data enrich the evolutionary and functional characterization of dip2 genes and provide significant insights into the identification and application of other homologs of DIP2.
Simulation of Post‐Combustion CO2 Capture, a Comparison among Absorption, Adsorption and Membranes
Authors: Anselmi Hélène , Mirgaux Olivier , Bounaceur Roda , Patisson Fabrice 
Published: January 2019

AbstractPost‐combustion CO2 capture was studied in the favorable context where the captured CO2 can be reused in a neighboring industrial process. Three technologies for CO2 capture, absorption by amines, adsorption on activated carbon, and separation using polymer membranes, were considered, modeled and compared. The three capture processes were designed for achieving the same performances. The models were integrated in a commercial flowsheeting software. The results show that, for a targeted CO2 purity of 95 %, the membrane process appears to be the least energy consuming. A next step will be to quantify the environmental benefits using life cycle assessment.
Double Cu‐Catalyzed Direct Csp3−H Azidation/CuAAC Reaction: A Direct Approach towards Demanding Triazole Conjugates
Authors: Brandhofer Tobias , Özdemir Aysegül , Gini Andrea , Mancheño Olga García 
Published: January 2019

AbstractThe first one‐pot procedure for the double copper(I)‐catalyzed oxidative Csp3−H azidation–CuAAC process, implying unstable azide intermediates and easy‐to‐remove reagents under water‐tolerant conditions, is presented. The combination of tert‐butyl hydroperoxide as oxidant and TMSN3 as azide source for the C−H bond azidation, which produces harmless side‐products such as tBuOH and H2O, probed to be perfectly compatible with the following cycloaddition step. Highly demanding 1,2,3‐triazoles could be then directly obtained in good overall yields by extraction or simple crystallization, thus avoiding chromatography purifications. The potential of this methodology, has also being highlighted by the successful reaction of alkynes presenting interesting complex biological moieties based for example on biotin, DNA base or cinchona alkaloid units.
Effective sapphire repellency treatment to reduce fouling of a focused beam reflectance measurement (FBRM) probe in bituminous systems
Authors: Saraka Colin , Machado Márcio B. , Webster Scott E. , Gomez Clara , Kresta Suzanne M. 
Published: January 2019

AbstractThe use of a focused beam reflectance measurement (FBRM) probe to track the chord length distribution dynamics in a bituminous system can be very challenging. Material coats the sapphire window of the probe and the quality of the data is compromised. The fouling index is a parameter used to assess the quality of the FBRM data. It is provided by the software and is the percentage similarity between two consecutive scans of the instrument, indicating how much of the reading has not changed due to material that is stuck to the optical window. When the FBRM was used in bitumen froth, the fouling index was higher than 90 %. In this work the significant reduction in fouling achieved with a sapphire repellency treatment is presented. The reduction in fouling was sufficient to detect broad trends in the FBRM data that will be used in future studies but was not sufficient to ensure quantitative measurement of the chord length distribution.
Energy Transfer of Peptide Ions Colliding with a Self‐Assembled Monolayer Surface. The Influence of Peptide Ion Size
Authors: Gu Meng , Yang Li , Hase William L , Sun Jianmin , Zhang Jiaxu 
Published: January 2019

Summary of main observation and conclusionAtomistic dynamics of protonated polyglycine, glyn‐H+ (n = 3, 5, and 7), colliding with a fluorinated octanethiol self‐assembled monolayer (F‐SAM) surface has been studied by trajectory calculations. The effects of peptide size on the collision processes and energy transfer efficiencies are emphasized and discussed in detail. The simulations show that the fraction of trapping, which is related to the soft‐landing process, dramatically drops with the increase in collision energy, but gently increases with the peptide size. The average energy transfer to the peptide ion's internal degrees of freedom, ΔEint, is compared with previous experiments. The limiting probability Po of energy transfer to the surface is given by fitting a function of Poexp(–b/Ei). Our results suggest that the efficiencies of energy transfer are less dependent on the masses, even the categories of the peptide ions, and are determined by the character of the surfaces.
Diamondoid Amino Acid‐Based Peptide Kinase A Inhibitor Analogues
Authors: Müller Janis , Kirschner Romina A. , Berndt Jan‐Philipp , Wulsdorf Tobias , Metz Alexander , Hrdina Radim , Schreiner Peter R. , Geyer Armin , Klebe Gerhard 
Published: January 2019

AbstractThe incorporation of diamondoid amino acids (DAAs) into peptide‐like drugs is a general strategy to improve lipophilicity, membrane permeability, and metabolic stability of peptidomimetic pharmaceuticals. We designed and synthesized five novel peptidic DAA‐containing kinase inhibitors of protein kinase A using a sophisticated molecular dynamics protocol and solid‐phase peptide synthesis. By means of a thermophoresis binding assay, NMR, and crystal structure analysis, we determined the influence of the DAAs on the secondary structure and binding affinity in comparison to the native protein kinase inhibitor, which is purely composed of proteinogenic amino acids. Affinity and binding pose are largely conserved. One variant showed 6.5‐fold potency improvement, most likely related to its increased side chain lipophilicity. A second variant exhibited slightly decreased affinity presumably due to loss of hydrogen‐bond contacts to surrounding water molecules of the first solvation shell.
Phase 1/2 study of DFP‐10917 administered by continuous intravenous infusion in patients with recurrent or refractory acute myeloid leukemia
Authors: Kantarjian Hagop M. , Jabbour Elias J. , Garcia‐Manero Guillermo , Kadia Tapan M. , DiNardo Courtney D. , Daver Naval G. , Borthakur Gautam , Jain Nitin , Waukau Jane B. , Kwari Monica I. , Ravandi Farhad , Anderson Barry D. , Iizuka Kenzo , Jin Cheng , Zhang Chun , Plunkett William K. 
Published: January 2019

AbstractBackgroundDFP‐10917, a deoxycytidine nucleoside analogue, has a unique mechanism of action resulting in leukemic cell death when administered for prolonged periods at low doses. The current phase 1/2 study investigated the safety, maximum tolerated dose, and evidence of antileukemic activity for DFP‐10917 administered by 7‐day or 14‐day continuous intravenous infusion in patients with recurrent or refractory acute myeloid leukemia (AML).MethodsIn the phase 1 dose escalation portion of the study, patients were administered DFP‐10917 by 7‐day continuous intravenous infusion plus 21‐day rest (stage 1) or 14‐day continuous intravenous infusion plus 14‐day rest (stage 2). The primary objectives of phase 1 were to determine the maximum tolerated dose, the phase 2 dose, and the dose‐limiting toxicities (DLTs) of DFP‐10917. The primary objectives of phase 2 were to evaluate the overall response rate of DFP‐10917 using complete response (CR), CR without platelet recovery (CRp), CR with incomplete blood count recovery (CRi) or partial response.ResultsIn stage 1 of phase 1 (4‐35 mg/m2/day as a 7‐day continuous intravenous infusion), a DLT of grade 3 diarrhea occurred at a dose of 35 mg/m2/day. In stage 2 of phase 1, a dose of 10 mg/m2/day as a 14‐day continuous intravenous infusion resulted in DLTs of prolonged hypocellularity, abdominal pain, diarrhea, and vomiting. The dose of 6 mg/m2/day as a 14‐day continuous intravenous infusion was found to be well tolerated and was selected for phase 2. Response rates in patients in phase 2 (N = 29) were 20.7% CR, 3.4% CRp, and 24.1% CRi. The overall response rate was 48.3% (95% confidence interval, 29.4%‐67.5%).ConclusionsDFP‐10917 as a 14‐day continuous intravenous infusion at a dose of 6 mg/m2/day can be administered safely and appears to be effective in patients with recurrent or refractory AML. A phase 3 investigation comparing DFP‐10917 monotherapy versus standard of care in an early recurrent or refractory AML setting is warranted.
Pharmacokinetics of Once‐Daily Extended‐Release Tacrolimus Tablets Versus Twice‐Daily Capsules in De Novo Liver Transplant
Authors: DuBay Derek A. , Teperman Lewis , Ueda Kimi , Silverman Andrew , Chapman William , Alsina Angel E. , Tyler Carmelina , Stevens Daniel R. 
Published: January 2019

AbstractThe pharmacokinetics of once‐daily extended‐release tacrolimus tablets (LCPT) in de novo liver transplantation have not been previously reported. In this phase II, randomized, open‐label study, de novo liver transplant recipients were randomized to LCPT 0.07–0.13 mg/kg/day (taken once daily; n = 29) or twice‐daily immediate‐release tacrolimus capsules (IR‐Tac) at 0.10–0.15 mg/kg/day (divided twice daily; n = 29). Subsequent doses of both drugs were adjusted to maintain tacrolimus trough concentrations of 5 to 20 ng/mL through day 90, and 5–15 ng/mL thereafter. Twenty‐four‐hour pharmacokinetic profiles were obtained on days 1, 7, and 14, with trough concentration and efficacy/safety monitoring through year 1. Similar proportions of patients in both groups achieved therapeutic trough concentrations on days 7 and 14 (day 7: LCPT = 78%, IR‐Tac = 75%; day 14: LCPT = 86%, IR‐Tac = 91%) as well as similar systemic and peak exposure. There was a robust correlation between drug concentration at time 0 and area under the concentration‐time curve for both LCPT and IR‐Tac (respectively, day 7: r = 0.86 and 0.79; day 14: r = 0.93 and 0.86; P < .0001 for all). Dose adjustments during days 1 to 14 were frequent. Thirty‐five patients completed the extended‐use period. No significant differences in adverse events were seen between groups. Incidence of biopsy‐proven acute rejection (LCPT = 6 and IR‐Tac = 4) was similar on day 360. Between formulations, overall exposure was similar at 1 week after transplant with the characteristic delayed‐release pharmacokinetic profile of LCPT demonstrated in this novel population. These data support further investigation of the safety and efficacy of LCPT in de novo liver transplantation.
Retinoic acid signaling reduction recapitulates the effects of alcohol on embryo size
Authors: Shukrun Natalie , Shabtai Yehuda , Pillemer Graciela , Fainsod Abraham 
Published: January 2019

SummaryIntrauterine growth restriction (IUGR) is commonly observed in human pregnancies and can result in severe clinical outcomes. IUGR is observed in Fetal Alcohol Syndrome (FAS) fetuses as a result of alcohol (ethanol) exposure during pregnancy. To further understand FAS, the severe form of Fetal Alcohol Spectrum Disorder, we performed an extensive quantitative analysis of the effects of ethanol on embryo size utilizing our Xenopus model. Ethanol‐treated embryos exhibited size reduction along the anterior–posterior axis. This effect was evident primarily from the hindbrain caudally, while rostral regions appeared refractive to ethanol‐induced size changes, also known as asymmetric IUGR. Interestingly, some embryo batches in addition to shortening from the hindbrain caudally also exhibited an alcohol‐dependent reduction of the anterior head domain, known as symmetric IUGR. To study the connection between ethanol exposure and reduced retinoic acid levels we treated embryos with the retinaldehyde dehydrogenase inhibitors, DEAB and citral. Inhibition of retinoic acid biosynthesis recapitulated the growth defects induced by ethanol affecting mainly axial elongation from the hindbrain caudally. To study the competition between ethanol clearance and retinoic acid biosynthesis we demonstrated that, co‐exposure to alcohol reduces the teratogenic effects of treatment with retinol (vitamin A), the retinoic acid precursor. These results further support the role of retinoic acid in the regulation of axial elongation.
Avoidant restrictive food intake disorder: First do no harm
Authors: Katzman Debra K. , Norris Mark L. , Zucker Nancy 
Published: January 2019

AbstractObjectiveThis opinion piece offers some considerations, both medical and psychological, for the use of nasogastric tube (NGT) feedings in the treatment of avoidant restrictive food intake disorder (ARFID) in children and adolescents.MethodAlthough there is empirical support for the use of NGT feedings in the treatment of anorexia nervosa, this evidence base does not exist for the treatment of ARFID. As such, there is need to delineate pragmatic considerations in the use of this procedure.ResultsIssues of medical necessity notwithstanding, we advise that the use of this procedure be considered more cautiously due to the oral sensitivities inherent in many individuals with ARFID and the potential psychological consequences. These sensitivities may make the experience of NGT feedings particularly aversive, with the potential of creating iatrogenic conditioned food aversions.DiscussionThis article encourages clinicians to give careful thought and attention when considering NGT feedings in children and adolescents with ARFID.
The independent and combined effects of floral traits distinguishing two pollination ecotypes of a moth‐pollinated orchid
Authors: Trunschke Judith , Sletvold Nina , Ågren Jon 
Published: January 2019

AbstractIdentifying traits and agents of selection involved in local adaptation is important for understanding population divergence. In southern Sweden, the moth‐pollinated orchid Platanthera bifolia occurs as a woodland and a grassland ecotype that differ in dominating pollinators. The woodland ecotype is taller (expected to influence pollinator attraction) and produces flowers with longer spurs (expected to influence efficiency of pollen transfer) compared to the grassland ecotype. We examined whether plant height and spur length affect pollination and reproductive success in a woodland population, and whether effects are non‐additive, as expected for traits influencing two multiplicative components of pollen transfer. We reduced plant height and spur length to match trait values observed in the grassland ecotype and determined the effects on pollen removal, pollen receipt, and fruit production. In addition, to examine the effects of naturally occurring variation, we quantified pollinator‐mediated selection through pollen removal and seed production in the same population. Reductions of plant height and spur length decreased pollen removal, number of flowers receiving pollen, mean pollen receipt per pollinated flower, and fruit production per plant, but no significant interaction effect was detected. The selection analysis demonstrated pollinator‐mediated selection for taller plants via female fitness. However, there was no current selection mediated by pollinators on spur length, and pollen removal was not related to plant height or spur length. The results show that, although both traits are important for pollination success and female fitness in the woodland habitat, only plant height was sufficiently variable in the study population for current pollinator‐mediated selection to be detected. More generally, the results illustrate how a combination of experimental approaches can be used to identify both traits and agents of selection.