bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of polycationic amphiphilic cyclodextrin nanoparticles for anticancer drug delivery
Authors: Varan Gamze , Benito Juan M , Mellet Carmen Ortiz , Bilensoy Erem 
Published: July 2017

Background: Paclitaxel is a potent anticancer drug that is effective against a wide spectrum of cancers. To overcome its bioavailability problems arising from very poor aqueous solubility and tendency to recrystallize upon dilution, paclitaxel is commercially formulated with co-solvents such as Cremophor EL® that are known to cause serious side effects during chemotherapy. Amphiphilic cyclodextrins are favored oligosaccharides as drug delivery systems for anticancer drugs, having the ability to spontaneously form nanoparticles without surfactant or co-solvents. In the past few years, polycationic, amphiphilic cyclodextrins were introduced as effective agents for gene delivery in the form of nanoplexes. In this study, the potential of polycationic, amphiphilic cyclodextrin nanoparticles were evaluated in comparison to non-ionic amphiphilic cyclodextrins and core–shell type cyclodextrin nanoparticles for paclitaxel delivery to breast tumors. Pre-formulation studies were used as a basis for selecting the suitable organic solvent and surfactant concentration for the novel polycationic cyclodextrin nanoparticles. The nanoparticles were then extensively characterized with particle size distribution, polydispersity index, zeta potential, drug loading capacity, in vitro release profiles and cytotoxicity studies.Results: Paclitaxel-loaded cyclodextrin nanoparticles were obtained in the diameter range of 80−125 nm (depending on the nature of the cyclodextrin derivative) where the smallest diameter nanoparticles were obtained with polycationic (PC) βCDC6. A strong positive charge also helped to increase the loading capacity of the nanoparticles with paclitaxel up to 60%. Interestingly, cyclodextrin nanoparticles were able to stabilize paclitaxel in aqueous solution for 30 days. All blank cyclodextrin nanoparticles were demonstrated to be non-cytotoxic against L929 mouse fibroblast cell line. In addition, paclitaxel-loaded nanoparticles have a significant anticancer effect against MCF-7 human breast cancer cell line as compared with a paclitaxel solution in DMSO.Conclusion: According to the results of this study, both amphiphilic cyclodextrin derivatives provide suitable nanometer-sized drug delivery systems for safe and efficient intravenous paclitaxel delivery for chemotherapy. In the light of these studies, it can be said that amphiphilic cyclodextrin nanoparticles of different surface charge can be considered as a promising alternative for self-assembled nanometer-sized drug carrier systems for safe and efficient chemotherapy.
Debiasing the NEOWISE Cryogenic Mission Comet Populations
Authors: Bauer James M. , Grav Tommy , Fernández Yanga R. , Mainzer A. K. , Kramer Emily A. , Masiero Joseph R. , Spahr Timothy , Nugent C. R. , Stevenson Rachel A. , Meech Karen J. , Cutri Roc M. , Lisse Carey M. , Walker Russell , Dailey John W. , Rosser Joshua , Krings Phillip , Ruecker Kinjal , Wright Edward L. ,   the NEOWISE Team
Published: July 2017

Abstract
We use NEOWISE data from the four-band and three-band cryogenic phases of the Wide-field Infrared Survey Explorer mission to constrain size distributions of the comet populations and debias measurements of the short- and long-period comet (LPC) populations. We find that the fit to the debiased LPC population yields a cumulative size−frequency distribution (SFD) power-law slope (β) of −1.0 ± 0.1, while the debiased Jupiter-family comet (JFC) SFD has a steeper slope with β = −2.3 ± 0.2. The JFCs in our debiased sample yielded a mean nucleus size of 1.3 km in diameter, while the LPCs’ mean size is roughly twice as large, 2.1 km, yielding mean size ratios (

) that differ by a factor of 1.6. Over the course of the 8 months of the survey, our results indicate that the number of LPCs passing within 1.5 au are a factor of several higher than previous estimates, while JFCs are within the previous range of estimates of a few thousand down to sizes near 1.3 km in diameter. Finally, we also observe evidence for structure in the orbital distribution of LPCs, with an overdensity of comets clustered near 110° inclination and perihelion near 2.9 au that is not attributable to observational bias.
ALMA Observations of the Gravitational Lens SDP.9
Authors: Wong Kenneth C. , Ishida Tsuyoshi , Tamura Yoichi , Suyu Sherry H. , Oguri Masamune , Matsushita Satoki 
Published: July 2017

Abstract
We present long-baseline ALMA observations of the strong gravitational lens H-ATLAS J090740.0−004200 (SDP.9), which consists of an elliptical galaxy at

lensing a background submillimeter galaxy into two extended arcs. The data include Band 6 continuum observations, as well as CO J = 6−5 molecular line observations, from which we measure an updated source redshift of

. The image morphology in the ALMA data is different from that of the Hubble Space Telescope (HST) data, indicating a spatial offset between the stellar, gas, and dust component of the source galaxy. We model the lens as an elliptical power law density profile with external shear using a combination of archival HST data and conjugate points identified in the ALMA data. Our best model has an Einstein radius of

and a slightly steeper than isothermal mass profile slope. We search for the central image of the lens, which can be used constrain the inner mass distribution of the lens galaxy including the central supermassive black hole, but do not detect it in the integrated CO image at a 3σ rms level of 0.0471 Jy km s−1.
Imatinib and Nilotinib Off-Target Effects on Human NK Cells, Monocytes, and M2 Macrophages
Authors: Bellora Francesca , Dondero Alessandra , Corrias Maria Valeria , Casu Beatrice , Regis Stefano , Caliendo Fabio , Moretta Alessandro , Cazzola Mario , Elena Chiara , Vinti Luciana , Locatelli Franco , Bottino Cristina , Castriconi Roberta 
Published: July 2017

Abstract
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells. In NB, neither drug reduced the expression of ligands for activating NK receptors or upregulated that of HLA class I, B7-H3, PD-L1, and PD-L2, molecules that might limit NK cell function. Interestingly, TKIs modulated the chemokine receptor repertoire of immune cells. Acting at the transcriptional level, they increased the surface expression of CXCR4, an effect observed also in NK cells and monocytes of patients receiving imatinib for chronic myeloid leukemia. Moreover, TKIs reduced the expression of CXCR3 (in NK cells) and CCR1 (in monocytes). Monocytes also decreased the expression of M-CSFR, and low numbers of cells underwent differentiation toward macrophages. M0 and M2 macrophages were highly resistant to TKIs and maintained their phenotypic and functional characteristics. Importantly, also in the presence of TKIs, the M2 immunosuppressive polarization was reverted by TLR engagement, and M1-oriented macrophages fully activated autologous NK cells. Our results contribute to better interpreting the off-target efficacy of TKIs in tumors and to envisaging strategies aimed at facilitating antitumor immune responses.
Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines Macrophage Responses during Renal Fibrosis
Authors: Steiger Stefanie , Kumar Santhosh V. , Honarpisheh Mohsen , Lorenz Georg , Günthner Roman , Romoli Simone , Gröbmayr Regina , Susanti Heni-Eka , Potempa Jan , Koziel Joanna , Lech Maciej 
Published: July 2017

Abstract
Activation of various innate immune receptors results in IL-1 receptor–associated kinase (IRAK)-1/IRAK-4–mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD). Our study assessed the contribution of macrophages in CKD and the role of IRAK-M in modulating disease progression. To evaluate the effect of IRAK-M in chronic renal injury in vivo, a mouse model of unilateral ureteral obstruction (UUO) was employed. The expression of IRAK-M increased within 2 d after UUO in obstructed compared with unobstructed kidneys. Mice deficient in IRAK-M were protected from fibrosis and displayed a diminished number of alternatively activated macrophages. Compared to wild-type mice, IRAK-M–deficient mice showed reduced tubular injury, leukocyte infiltration, and inflammation following renal injury as determined by light microscopy, immunohistochemistry, and intrarenal mRNA expression of proinflammatory and profibrotic mediators. Taken together, these results strongly support a role for IRAK-M in renal injury and identify IRAK-M as a possible modulator in driving an alternatively activated profibrotic macrophage phenotype in UUO-induced CKD.
N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1
Authors: Lawton Samira K. , Xu Fengyun , Tran Alphonso , Wong Erika , Prakash Arun , Schumacher Mark , Hellman Judith , Wilhelmsen Kevin 
Published: July 2017

Abstract
N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis. We also found that the administration of NADA increases survival in endotoxemic mice. Additionally, NADA reduces blood levels of the neuropeptide calcitonin gene-related peptide but increases the neuropeptide substance P in LPS-treated mice. We demonstrate that the anti-inflammatory effects of NADA are mediated by TRPV1 expressed by nonhematopoietic cells and provide data suggesting that neuronal TRPV1 may mediate NADA’s anti-inflammatory effects. These results indicate that NADA has novel TRPV1-dependent anti-inflammatory properties and suggest that the endovanilloid system might be targeted therapeutically in acute inflammation.
La profession vétérinaire en Europe
Authors: Chambon Thierry 
Published: July 2017

The veterinary profession in Europe.
The survey of veterinarians across Europe received 13000 responses from 24 FVE members. The results establish 243000 veterinarians who care for 157 million companion animals and 342 million cattle, sheep, pigs and goats. It is a young profession with 44 % veterinarians aged under 40, and an equal profession with a near balance of male and female. Veterinary medicine is flexible where 17 % are working part time, while 21 % have at least two different jobs. Unemployment is low, 3 %. It results that veterinarians are satisfied with their choice of career. Veterinary practice is the most important area of employment. Veterinarians feel confident about their prospects. They believe that more veterinarians will be needed in the areas of animal welfare, disease control and environment. But too many veterinarians are emerging, with insufficient skills to perform daily tasks, and need of specialization.
Tema 1: Spildesign i Serious Games - en didaktisk udfordring?
Authors: Helms Niels Henrik , Rahbek Jess Uhre 
Published: July 2017

I dette bidrag diskuteres problemfeltet ”didaktisk spildesign” i forhold til principper for godt spildesign og didaktisk design. På baggrund af forskellige forskningsbidrag og udviklingen af et spilelement til støtte for behandlingen af veteraner med PTSD undersøges forholdet mellem spil og læring. Artiklen fremhæver udfordringerne ved at skabe koblinger mellem spillets rationalitet og logik i forhold til sammenhænge, hvor det ønskede resultat er læring. De forskellige rationaliteter skaber behovet for en flerfaglig udviklingsproces, men samtidig understreges det, at en sådan proces skaber behov for et struktureret metadesign, hvor forståelse af strukturer og processer i flerfaglige samarbejder gøres eksplicitte, og øger sandsynligheden for, at forskellighederne bliver ressourcer og ikke genererer atomiserede udviklingsforløb. Afslutningsvis diskuteres spillet som et særligt læringsrum, og hvorfor og hvordan det kan tænkes i forhold til andre læringsrum.
Revitalisering af PBL i videregående uddannelser gennem Learning Design
Authors: Davidsen Jacob , Konnerup Ulla 
Published: July 2017

Gennem de sidste 10 år har større studenteroptag og begrænsede ressourcer på Aalborg Universitet (AAU) ledt til flere klassiske forelæsninger, hvilket har resulteret i en udvanding og af de grundlæggende PBL principper. Vi argumenterer for, at en revitalisering af PBL gennem brugen af Learning Designs er en mulighed til at kvalificere den tilgang til læring og uddannelse, som i mere end 40 år har været kendetegn for AAU. Med afsæt i en case fra Kommunikation og Digitale Medier (KDM) afdækker vi, hvordan Learning Design kan fungere som et deskriptivt sprog og en form, der kan danne grundlag for udvikling og kvalificering af kurser, undervisnings- og læringsaktiviteter. Indenfor feltet Learning Design spores to retninger: 1) en retning med fokus effektivisering og standardisering af uddannelse og 2) en retning med fokus på udvikling, formgivning og kvalificering af uddannelse. I denne artikel diskuterer vi potentialer og udfordringer ved at konceptualisere PBL forløb som et Learning Design.

Abstract
Through the last 10 years, increasing numbers of students and a lack of resources at Aalborg University (AAU) have resulted in more classical lectures, which have occasioned a watering down and ritualization of the founding principles of PBL. In this paper, we argue that a revitalization of the PBL at AAU could be facilitated through the application of Learning Design. By using a case from Communication and Digital Media (CDM) we explore how Learning Design can act as a descriptive language and form, which can support the development of courses, teaching, and learning activities. Within the field of Learning Design two positions can be identified: 1) a position focusing on finding more effect and standard ways of running education, and 2) a position focusing on development and design of education. In this paper we discuss potentials and challenges of conceptualizing PBL as a Learning Design.
Real-time monitoring of superoxide anion radical generation in response to wounding: electrochemical study
Authors: Prasad Ankush , Kumar Aditya , Matsuoka Ryo , Takahashi Akemi , Fujii Ryo , Sugiura Yamato , Kikuchi Hiroyuki , Aoyagi Shigeo , Aikawa Tatsuo , Kondo Takeshi , Yuasa Makoto , Pospíšil Pavel , Kasai Shigenobu 
Published: July 2017

BackgroundThe growth and development of plants is deleteriously affected by various biotic and abiotic stress factors. Wounding in plants is caused by exposure to environmental stress, mechanical stress, and via herbivory. Typically, oxidative burst in response to wounding is associated with the formation of reactive oxygen species, such as the superoxide anion radical (O2•−), hydrogen peroxide (H2O2) and singlet oxygen; however, few experimental studies have provided direct evidence of their detection in plants. Detection of O2•−formation in plant tissues have been performed using various techniques including electron paramagnetic resonance spin-trap spectroscopy, epinephrine-adrenochrome acceptor methods, staining with dyes such as tetrazolium dye and nitro blue tetrazolium (NBT); however, kinetic measurements have not been performed. In the current study, we provide evidence of O2•−generation and its kinetics in the leaves of spinach (Spinacia oleracea) subjected to wounding.MethodsReal-time monitoring of O2•−generation was performed using catalytic amperometry. Changes in oxidation current for O2•−was monitored using polymeric iron-porphyrin-based modified carbon electrodes (φ = 1 mm) as working electrode with Ag/AgCl as the reference electrode.ResultThe results obtained show continuous generation of O2•−for minutes after wounding, followed by a decline. The exogenous addition of superoxide dismutase, which is known to dismutate O2•−to H2O2, significantly suppressed the oxidation current.ConclusionCatalytic amperometric measurements were performed using polymeric iron-porphyrin based modified carbon electrode. We claim it to be a useful tool and a direct method for real-time monitoring and precise detection of O2•−in biological samples, with the potential for wide application in plant research for specific and sensitive detection of O2•−.
Construction of afurnull mutant and RNA-sequencing provide deeper global understanding of theAliivibrio salmonicidaFur regulon
Authors: Thode Sunniva Katharina , Bækkedal Cecilie , Söderberg Jenny Johansson , Hjerde Erik , Hansen Hilde , Haugen Peik 
Published: July 2017

BackgroundThe ferric uptake regulator (Fur) is a transcription factor and the main regulator of iron acquisition in prokaryotes. When bound to ferric iron, Fur recognizes its DNA binding site and generally executes its function by repressing transcription of its target genes. Due to its importance in virulence, the Fur regulon is well studied for several model bacteria. In our previous work, we used computational predictions and microarray to gain insights into Fur-regulation inAliivibrio salmonicida, and have identified a number of genes and operons that appear to be under direct control of Fur. To provide a more accurate and deeper global understanding of the biological role of Fur we have now generated anA. salmonicida furknock-out strain and used RNA-sequencing to compare gene expression between the wild-type andfurnull mutant strains.ResultsAnA. salmonicida furnull mutant strain was constructed. Biological assays demonstrate that deletion offurresults in loss of fitness, with reduced growth rates, and reduced abilities to withstand low-iron conditions, and oxidative stress. When comparing expression levels in the wild-type and thefurnull mutant we retrieved 296 differentially expressed genes distributed among 18 of 21 functional classes of genes. A gene cluster encoding biosynthesis of the siderophore bisucaberin represented the highest up-regulated genes in thefurnull mutant. Other highly up-regulated genes all encode proteins important for iron acquisition. Potential targets for the RyhB sRNA was predicted from the list of down-regulated genes, and significant complementarities were found between RyhB and mRNAs of thefur,sodB,cysNand VSAL_I0422 genes. Other sRNAs with potential functions in iron homeostasis were identified.ConclusionThe present work provides by far the most comprehensive and deepest understanding of the Fur regulon inA. salmonicidato date. Our data also contribute to a better understanding of how Fur plays a key role in iron homeostasis in bacteria in general, and help to show how Fur orchestrates iron uptake when iron levels are extremely low.
Hyporheic hot moments: Dissolved oxygen dynamics in the hyporheic zone in response to surface flow perturbations
Authors: Kaufman Matthew H. , Cardenas M. Bayani , Buttles Jim , Kessler Adam J. , Cook Perran L. M. 
Published: July 2017

AbstractDissolved oxygen (DO) is a key environmental variable that drives and feeds back with numerous processes. In the aquatic sediment that makes up the hyporheic zone, DO may exhibit pronounced spatial gradients and complex patterns which control the distribution of a series of redox processes. Yet, little is known regarding the dynamics of hyporheic zone DO, especially under transitional flow regimes. Considering the natural tendency of rivers to be highly responsive to external forcing, these temporal dynamics are potentially just as important and pronounced as the spatial gradients. Here we use laboratory flume experiments and multiphysics flow and reactive transport modeling to investigate surface flow controls on the depth of oxygen penetration in the bed as well as the area of oxygenated sediment. We show that the hyporheic zone DO conditions respond over time scales of hours‐to‐days when subjected to practically instantaneous surface flow perturbations. Additionally, the flume experiments demonstrate that hyporheic zone DO conditions respond faster to surface flow acceleration than to deceleration. Finally, we found that the morphology of the dissolved oxygen plume front depends on surface flow acceleration or deceleration. This study thus shows that the highly dynamic nature of typical streams and rivers drives equally dynamic redox conditions in the hyporheic zone. Because the redox conditions and their distribution within the hyporheic zone are important from biological, ecological, and contaminant perspectives, this hyporheic redox dynamism has the potential to impact system scale aquatic chemical cycles.
Monitoring and simulation of salinity changes in response to tide and storm surges in a sandy coastal aquifer system
Authors: Huizer S. , Karaoulis M. C. , Oude Essink G. H. P. , Bierkens M. F. P. 
Published: July 2017

AbstractTidal dynamics and especially storm surges can have an extensive impact on coastal fresh groundwater resources. Combined with the prospect of sea‐level rise and the reliance of many people on these resources, this demonstrates the need to assess the vulnerability of coastal areas to these threats. In this study, we investigated the impact of tides and storm surges on coastal groundwater at a pilot location on the Dutch coast (viz., the Sand Engine). To monitor changes in groundwater salinity under a variety of conditions, we performed automated measurements with electrical resistivity tomography for a period of 2 months between November 2014 and January 2015. The obtained resistivity images were converted to salinity images, and these images served effectively as observations of the impact of tidal fluctuations, saltwater overwash during storm surges, and the recovery of the freshwater lens after land‐surface inundations. Most of the observed changes in groundwater head and salinity could be reproduced with a two‐dimensional variable‐density groundwater flow and salt transport model. This shows that groundwater models can be used to make accurate predictions of the impact of tides and storm surges on fresh groundwater resources, given a thorough understanding of the (local) system. Comparisons of measurements and model simulations also showed that morphological changes and wave run‐up can have a strong impact on the extent of land‐surface inundations in (low‐elevation) dynamic coastal environments, and can therefore substantially affect coastal fresh groundwater resources.