bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imatinib and everolimus in patients with progressing advanced chordoma: A phase 2 clinical study
Authors: Stacchiotti Silvia , Morosi Carlo , Lo Vullo Salvatore , Casale Alessandra , Palassini Elena , Frezza Anna Maria , Dinoi Gabriella , Messina Antonella , Gronchi Alessandro , Cavalleri Adalberto , Venturelli Elisabetta , Morelli Daniele , Pilotti Silvana , Collini Paola , Brich Silvia , Tamborini Elena , Mariani Luigi , Casali Paolo G. 
Published: September 2018

BackgroundWe present the results of an academic phase 2 study on imatinib plus everolimus in patients who have progressive advanced chordoma.MethodsIn January 2011, 43 adult chordoma patients were enrolled in the study and received imatinib 400 mg/day and everolimus 2.5 mg/day until progression or limiting toxicity. Eligible patients had progressed in the 6 months before study entry. PDGFRB, S6, and 4EBP1 expression and phosphorylation were evaluated by way of immunohistochemistry and/or western blotting. The primary endpoint was the overall response rate (ORR) according to Choi criteria. Secondary endpoints were RECIST 1.1 response, progression‐free survival (PFS), overall survival (OS), correlation between S6/4EBP1 phosphorylation and response.ResultsThirteen of 43 patients were pretreated with imatinib. Among 40 of the 43 patients who were evaluable by Choi criteria, the best responses were 9 with partial response (ORR, 20.9%), 24 with stable disease (SD) (ORR, 55.8%), and 7 with progressive disease (ORR, 16.3%). Forty‐two patients were evaluable by RECIST criteria, with 1 partial response (ORR, 2.3%), 37 stable disease (ORR, 86%), and 4 progressive disease (ORR, 9.3%). The median PFS according to Choi criteria was 11.5 months (range, 4.6‐17.6 months), and 58.8% and 48.1% of patients were progression‐free at 9 and 12 months, respectively. The median PFS by RECIST criteria was 14 months; the median OS was 47.1 months. When assessable, S6/4EBP1 was phosphorylated in a high and moderate/low proportion of tumor cells in responsive and nonresponsive patients, respectively. Toxicity caused a temporary and definitive treatment discontinuation in 60.5% and 30.2% of patients, respectively.ConclusionsImatinib plus everolimus showed a limited activity in progressing advanced chordoma. Interestingly, the amount of tumor cells activated for mammalian target of rapamycin effectors correlated with the response. Toxicity was not negligible.
Epsilon‐Fe2O3 Nanocrystals inside Mesoporous Silicas with Tailored Morphologies of Rod, Platelet and Donut
Authors: Li Jheng‐Guang , Fornasieri Giulia , Bleuzen Anne , Gich Martí , Impéror‐Clerc Marianne 
Published: September 2018

AbstractThe ϵ‐Fe2O3 polymorph of iron oxide, which has outstanding physical properties, is successfully stabilized inside mesoporous silica particles with tailored shapes. Using mesoporous silica particles with three different morphologies of rod, platelet and donut, we obtain ϵ‐Fe2O3/mesoporous silica nanocomposites. Iron oxide is loaded inside the porosity using a two steps impregnation cycle: solvent‐free impregnation followed by oxidation under 1000 °C. The amount of loaded iron oxide can be enhanced using two successive impregnation cycles. We fully characterise these nanocomposite particles with a wide panel of techniques to establish the exact amount of loaded iron inside the porosity, the nature of the iron oxide phase and the size of the nanocrystals. As a result, we conclude that ϵ‐Fe2O3 nanocrystals can be confined and stabilized in all types of morphologies, even inside the donut morphology which possesses closed mesopores.
Transforming a Diamagnetic Ordered Mesoporous Silica Monolith into a Room Temperature Permanent Magnet through Multiscale Control of the Magnetic Properties
Authors: Trannoy Virgile , Altenschmidt Laura , Fornasieri Giulia , Bordage Amélie , Rivière Eric , Beaunier Patricia , Bleuzen Anne 
Published: September 2018

AbstractPrussian blue analog (PBA) nanoparticles confined in the ordered mesoporosity of silica monoliths with two‐dimensional hexagonal structure are used as precursors and transformed into metal oxide or metal alloy by thermal treatment under oxidizing or reducing atmosphere. X‐ray diffraction and transmission electron microscopy show that, after appropriate thermal treatment, the ordered silica monoliths contain spherical nanocrystals of mixed oxide and metal alloy aligned along the cylindrical pore axis. Their size (4 nm) is controlled by the diameter of the cylindrical pores of the silica monolith and their aggregation state by the structure of the porosity and the synthesis route. Furthermore, the chemical composition of the starting PBA precisely determines that of the oxide or alloy nanocrystals. The magnetic properties of the monoliths, governed by strong interparticle interactions, are very sensitive to chemical composition, size and aggregation state of the nanoparticles. The multi‐scale control of the nanocomposite enables producing a light macroscopic permanent magnet, which is attracted to a NdBFe magnet at room temperature.
An automated and scalable formal process for detecting fault injection vulnerabilities in binaries
Authors: Given‐Wilson Thomas , Heuser Annelie , Jafri Nisrine , Legay Axel 
Published: September 2018

SummaryFault injection has increasingly been used both to attack software applications and to test system robustness. Detecting fault injection vulnerabilities has been approached with a variety of different but limited methods. This paper proposes an extension of a recently published general model checking based process to detect fault injection vulnerabilities in binaries. This new extension makes the general process scalable to real‐world implementations, which is demonstrated by detecting vulnerabilities in different cryptographic implementations.
Comparing feedback from faculty interactions and virtual assessment software in the development of psychomotor skills in preclinical fixed prosthodontics
Authors: Sadid‐Zadeh Ramtin , D'Angelo Elizabeth H. , Gambacorta Joseph 
Published: September 2018

AbstractThe purpose of this study was to determine the effectiveness of virtual assessment software as a means of immediate feedback for preclinical fixed prosthodontics course. The subjects of the study were second year dental students with no previous training in fixed prosthodontics. Nine students participated in the study. Participants completed 2 days of didactic training focused on the principles of tooth preparation and the use of intraoral scanners and virtual assessment software. Didactic training was followed by 12 sessions of practical exercises. Students were randomly assigned to one of three groups for training in the preparation of tooth no. 46 for a complete cast crown. Students received feedback from (a) faculty interaction only; (b) interactions with both faculty and virtual assessment software; or (c) interactions with only virtual assessment software. During Sessions 5, 10, and 12, students prepared tooth no. 46 for complete cast crown independently and without any immediate feedback to simulate a practical exam. Prepared teeth were collected at Sessions 5, 10, and 12, and two blinded faculty members assessed the teeth following an established rubric. Results from Session 12 showed that preparations that one of three students and two of three students respectively for student–faculty interaction and student–faculty–Compare software interaction groups did not meet acceptable standards. However, the students in student–Compare software interaction group generated acceptable preparations at week 12. These data suggest that immediate feedback via virtual assessment software may be as effective as one‐on‐one faculty instruction for dental students in fixed prosthodontics.
Community‐wide consequences of sexual dimorphism: evidence from nectar microbes in dioecious plants
Authors: Tsuji Kaoru , Fukami Tadashi 
Published: September 2018

AbstractIntraspecific trait variation is receiving renewed interest as a factor affecting the structure of multi‐species communities within and across trophic levels. One pervasive form of intraspecific trait variation is sexual dimorphism in animals and plants, which might exert large effects particularly on the communities of host‐associated organisms, but the extent of these effects is not well understood. We investigated whether host‐associated microbial communities developed differently in the floral nectar of female and male individuals of the dioecious shrubs, Eurya emarginata and E. japonica. We found that nectar‐colonizing microbes such as bacteria and fungi were more than twice as prevalent and, overall, more than 10 times as abundant in male flowers as in female flowers. Microbial species composition also differed between flower sexes. To examine potential mechanisms behind these differences, we manipulated the frequency of flower visitation by animals and the order of arrival of microbial species to nectar. Animal visitation frequency affected microbial communities more greatly in male flowers, while arrival order affected them more in female flowers. These sex‐specific effects appeared attributable to differences in how animals and microbes altered the chemical characteristics of nectar that limited microbial growth. Taken together, our results provide evidence that sexual dimorphism can have large effects on the structure of host‐associated communities.
Prophylactic treatment against GM‐CSF, but not IL‐17, abolishes relapses in a chronic murine model of multiple sclerosis
Authors: Uyttenhove Catherine , Gaignage Mélanie , Donckers Dominique , Nasr Zakia , Cheou Pamela , van Snick Jacques , D'Auria Ludovic , van Pesch Vincent 
Published: September 2018

AbstractThe pathogenic role of IL‐17 and GM‐CSF has been unravelled in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). However, in most models, EAE is characterised by a monophasic attack which is not representative of the relapsing nature nor the chronicity displayed in MS. Here, we used proteolipid protein peptide (PLP139‐151) to trigger EAE‐relapses (EAE‐II) in SJL mice that had recovered from a primary‐EAE episode (EAE‐I). This procedure resulted in severe and irreversible disease that, unlike EAE‐I, was not abolished by anti‐IL‐17‐mAb. In contrast, prophylactic anti‐GM‐CSF‐mAb treatment prevented EAE‐I and ‐II. Strikingly, the expression of T‐cell transcription factors and cytokines/chemokines in mice treated with anti‐GM‐CSF during both EAE episodes was silenced. Anti‐GM‐CSF‐mAb treatment administered only during EAE‐II did not completely prevent relapses but mice ultimately reached full recovery. Anti‐GM‐CSF treatment also strongly impaired and ultimately resolved monophasic MOG35‐55‐induced EAE in C57Bl/6 mice. In such protected mice, anti‐GM‐CSF treatment also prevented a further relapse induced by MOG‐revaccination. These results underscore the critical role of GM‐CSF on pro‐inflammatory mediator production. Furthermore, we observed a strong preventive and curative effect of anti‐GM‐CSF neutralisation in two EAE models, relapsing and chronic. Altogether these findings are relevant for further MS research.
Silica Gel Functionalized with 4‐Amino‐5‐(4pyridyl)‐4H‐1,2,4‐triazole‐3‐thiol and their Use as a Copper Sorbent and Electromediator for Voltammetric Detection of Ascorbic Acid
Authors: de Souza Magossi Maiara , Maraldi Vitor Alexandre , de Souza Magossi Mariana , Dias Filho Newton Luiz , Ribeiro do Carmo Devaney 
Published: September 2018

AbstractIn this work, the 3‐chloropropyl silica gel (SG) was prepared and organofunctionalized with 4‐amino‐5‐(4pyridyl)‐4H‐1,2,4‐triazole‐3‐thiol (SGA), that was characterized by infrared spectroscopy (FTIR) and cyclic voltammetry (CV). The cupric ions (Cu2+) sorption on the silica functionalized surface (CuSGA) were performed in aqueous solution, at room temperature. It was performed a systematic study about voltammetric behavior of CuSGA, where the cyclic voltammogram of graphite paste electrode modified with CuSGA exhibited a single redox pair with formal potential (Eθ′)=0.30 V assigned to the process Cu+/Cu2+, (KCl 1.0 mol L−1, v=20 mV s−1). The graphite paste electrode modified with CuSGA was sensitive to different concentrations of ascorbic acid and then an analytical curve could be constructed, with a linear response of 6.0×10−6 to 9.0×10−5 mol L−1 (R=0.9988) and a relative standard deviation of ±2.5 % (n=3). The detection limit (3σ) and amperometric sensitivity were 4.78×10−6 mol L−1 and 115.96 mA/mol L−1, respectively.
A Novel Sediment Microbial Fuel Cell Based Sensor for On‐Line and in situ Monitoring Copper Shock in Water
Authors: Wu Shaosong , Deng Huan , Han Cheng , Liu Li , Zhong Wenhui 
Published: September 2018

AbstractTo online and in situ monitor the heavy metal shock in water, a novel sediment microbial fuel cell based sensor was developed with anode being inserted into flooded soil and cathode submerged in overlaying water. Immediately after CuSO4 solutions were added into the overlaying water, the voltage signal generated by the sensor reached a peak and the increment from baseline voltage to peak voltage increased linearly with Cu2+ concentrations up to 160 mg L−1. After Cu2+ shock, charge transfer resistance (Rct) of anode and cathode was determined by using electrochemical impedance spectroscopy. Soil DNA and RNA was extracted and 16S rRNA and 16S rRNA gene of dominant exoelectrogenic bacteria (Geobacter and Clostridium) was quantified. Result showed that Cu2+ shock decreased cathodic charge transfer resistance (Rct) but did not affect anodic Rct. The addition of 320 mg L−1 Cu2+ significantly reduced abundance and activity of Geobacter and Clostridium in surface soil (0–3 cm in depth) but had no effect on exoelectrogenic bacteria in deeper soil. Moreover, baseline voltage was stable after Cu2+ shock. The result indicates that the sensor could online and in situ monitor Cu2+ shock which increased voltage signal by promoting cathodic reaction without dramatically inhibiting exoelectrogenic bacteria.
Pattern Recognition of Diabetes Related Biomarkers
Authors: Stefan‐van Staden Raluca‐Ioana , Mitrofan Grigorina , Ionescu‐Tirgoviste Constantin 
Published: September 2018

AbstractFour stochastic microsensors were proposed for the molecular recognition of insulin, Proinsulin C Peptide (55–89), leptin, adiponectin and CRP in serum samples. The microsensors were design by physical immobilization of protoporphyrin PIX, phthalocyanine‐BODIPY dye (BODIPY=boron dipyrromethene), inulins such as TEX or ionic liquids such as L‐alanine‐tert‐butyl‐ester‐L‐lactate (L‐AlaC4‐Lac) in matrices such as diamond paste and Au‐TiO2/rGR paste. The proposed microsensors were reliable for the molecular recognition and quantification of the biomarkers. For the determination of Proinsulin C Peptide (55–89), insulin, leptin, adiponectin and CRP the immunoassay techniques are routinely used in clinical practice, requiring five types of detection kits, therefore one of the main advantage in using this method consists in determining in one run all the analytes.
A companion to the preclinical common data elements for pharmacologic studies in animal models of seizures and epilepsy. A Report of the TASK3 Pharmacology Working Group of the ILAE/AES Joint Translational Task Force
Authors: Barker‐Haliski Melissa , Harte‐Hargrove Lauren C. , Ravizza Teresa , Smolders Ilse , Xiao Bo , Brandt Claudia , Löscher Wolfgang 
Published: September 2018

SummaryPreclinical pharmacology studies in animal models of seizures and epilepsy have provided a platform to identify more than 20 antiseizure drugs in recent decades. To minimize variability in lab‐to‐lab studies and to harmonize approaches to data collection and reporting methodology in pharmacologic evaluations of the next generation of therapies, we present common data elements (CDEs), case report forms (CRFs), and this companion manuscript to help with the implementation of methods for studies in established preclinical seizure and epilepsy models in adult rodents. The development of and advocacy for CDEs in preclinical research has been encouraged previously by both clinical and preclinical groups. It is anticipated that adoption and implementation of these CDEs in preclinical studies may help standardize approaches to minimize variability and increase the reproducibility of preclinical studies. Moreover, they may provide a methodologic framework for pharmacology studies in atypical animal models or models in development, which may ultimately promote novel therapy development. In the present document, we refer selectively to animal models that have a long history of preclinical use, and in some cases, are clinically validated.
Mega‐blowouts in Qinghai–Tibet Plateau: Morphology, distribution and initiation
Authors: Luo Wanyin , Wang Zhongyuan , Lu Junfeng , Yang Linghai , Qian Guangqiang , Dong Zhibao , Bateman Mark D. 
Published: September 2018

AbstractBlowouts are wind‐eroded landforms that are widely distributed in the north‐eastern part in Qinghai–Tibet Plateau (QTP), China. These blowouts are thought to form in response to climate change and/or human activity but little is known about their morphodynamics. Using field surveys, remote sensing and geographic information system (GIS) spatial analysis, the distribution and morphology of blowouts are analysed and their initiation considered. Results show the QTP mega‐blowouts are some of the largest in the world. The orientations of the trough shaped blowouts are parallel with the prevailing wind, but the saucer and bowl‐shaped blowouts are influenced by bi‐directional transport. Whilst regional patterns of blowout shape and size were observed to reflect the extent of aeolian sediments and wind regimes, the relationship between the different morphological parameters showed consistency. During initial stages of development, the length to width ratios of blowouts increase rapidly with area but after they reach a mega size this relationship stabilizes as blowouts widen. Initial luminescence dating shows that blowouts appear to have initiated ~100 to 500 years ago, coinciding with the Little Ice Age (LIA) climate event when northwest winds are known to have intensified. Further work is required to confirm this initiation period and establish the significance of mega blowouts for landscape degradation and human activities. © 2018 John Wiley & Sons, Ltd.
Physically constrained data‐driven correction for reduced‐order modeling of fluid flows
Authors: Mohebujjaman M. , Rebholz L.G. , Iliescu T. 
Published: September 2018

SummaryWe have recently proposed a data‐driven correction reduced‐order model (DDC‐ROM) framework for the numerical simulation of fluid flows, which can be formally written as follows.
image The new DDC‐ROM was constructed by using reduced‐order model spatial filtering and data‐driven reduced‐order model closure modeling (for the Correction term) and was successfully tested in the numerical simulation of a two‐dimensional channel flow past a circular cylinder at Reynolds numbers Re = 100,Re = 500, and Re = 1000. In this paper, we propose a physically constrained DDC‐ROM (CDDC‐ROM), which aims at improving the physical accuracy of the DDC‐ROM. The new physical constraints require that the CDDC‐ROM operators satisfy the same type of physical laws (ie, the Correction term's linear component should be dissipative, and the Correction term's nonlinear component should conserve energy) as those satisfied by the fluid flow equations. To implement these physical constraints, in the data‐driven modeling step, we replace the unconstrained least squares problem with a constrained least squares problem. We perform a numerical investigation of the new CDDC‐ROM and standard DDC‐ROM for a two‐dimensional channel flow past a circular cylinder at Reynolds numbers Re = 100,Re = 500, and Re = 1000. To this end, we consider a reproductive regime as well as a predictive (ie, cross‐validation) regime in which we use as little as 50% of the original training data. The numerical investigation clearly shows that the new CDDC‐ROM is significantly more accurate than the DDC‐ROM in both regimes.
Commercial Fisheries of the Upper Mississippi River: A Century of Sustained Harvest
Authors: Klein Zachary B , Quist Michael C , Miranda Leandro E , Marron Michelle M , Steuck Michael J , Hansen Kirk A 
Published: September 2018

Abstract
Commercial harvest is often considered as a primary cause of fish population declines in marine and inland systems throughout the world. However, much of the data supporting the negative attributes of commercial harvest are derived from marine fisheries and may not be directly applicable to inland fisheries. In this study, over 60 years of commercial fishery data from the Upper Mississippi River (UMR) was synthesized to better understand how inland commercial fisheries function and to address concerns associated with the exploitation of aquatic resources in freshwater systems. Overall, total commercial harvest in the UMR remained relatively stable over the study period and did not negatively influence fish populations or recreational fisheries. Our results address concerns associated with inland fisheries and highlight how proper management and interagency partnerships result in consistent and productive fisheries over large spatial and temporal scales.
Effects of age and extraction solvent on phytochemical content and antioxidant activity of fresh Moringa oleifera L. leaves
Authors: Nobossé Pierre , Fombang Edith N. , Mbofung Carl M. F. 
Published: September 2018

AbstractAntioxidant activity (AOA) and phytochemical content of Moringa oleifera Lam leaves were determined as a function of their age and extraction solvent. Fresh Moringa leaves aged 30, 45, and 60 days were harvested and extracted with three solvents; methanol, ethanol, and water. AOA of leaf extracts was measured using radical scavenging assays (DPPH, ABTS, antiperoxide activity [APA]) and reducing assays (FRAP and total antioxidant capacity [TAC]), and these were correlated with total polyphenols (TPC), total flavonoids (TFC), and chlorophyll contents of leaves. Significant variability (p < 0.05) in TPC and AOA of Moringa leaf extracts was observed with age and extraction solvent as well as their interaction. TPC and TFC increased with maturity, except in aqueous extract. The 60‐day‐old leaves showed highest TPC, TFC, and tocopherol contents with highest DPPH activity. On their part, 30‐day‐old leaves recorded better vitamin C, chlorophyll, and carotenoids with highest ABTS activity and APA. Methanol was best extraction solvent for TPC (4.6 g GAE/100 g DM) while ethanol was for flavonoids (1.8 g CE/100 g DM). Ethanol extracts exhibited the highest DPPH activity (53.3%–71.1%), while both ethanolic and methanolic extracts had similar and higher ABTS+ activity (3.83–3.86 g AAE/100 g DM). Strong positive correlations (r ≥ 0.8; p < 0.05) were observed between chlorophyll content and DPPH, ABTS, and APA, suggesting that chlorophyll was the major contributor to AOA. TAC was highest in aqueous solvent. Free radical scavenging activity in Moringa leaves is positively correlated to chlorophyll, TFC, and TPC while reducing power is positively correlated to chlorophyll and TPC. AOA of fresh Moringa leaf extract is a function of its phytochemical content and is influenced by both the age of the leaves and the extraction solvent used. Methanolic and ethanolic extracts of 45‐day‐old Moringa leaves exhibited best antioxidant potentials.