bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Gene Expression Assays without Target Amplification
Authors: Trainor Deirdre , Tolley James , LaCerte Carl , Gaynor Barbara , Sewell Toddy , Jazdzewski Melinda , Lois Augusto , Gonzales Frank
Published: October 2018

Evaluating changes in gene expression is essential when identifying and validating new drug targets, however, the methods used to measure transcription are laborious, time-consuming and expensive ( e.g., RT-PCR, microarray or northern blot). High Performance Signal Amplification (HPSA™) gene expression assays quantitate particular mRNA targets directly in cell lysate samples using DNA probe hybridization and fluorescent signal amplification. The assay format eliminates the need for RNA purification prior to testing and does not require RT-PCR amplification. The HPSA™ protocol involves three steps carried out at 37°C in 96- or 384-well plates, making the technique amenable to automation. Cellular mRNA levels are quantitated relative to a standard curve consisting of purified in vitro RNA transcripts derived from cDNA clones. Assay sensitivity is in the low attomole range and can detect mRNA expressed at twenty copies per cell. A number of HPSA™ assays have been developed for cytokine, housekeeping and cytochrome P450 messages. Gene induction profiles were monitored in cell lines or peripheral blood mononuclear cells (PBMC) treated with activators such as phorbol 12-myristate-13-acetate (PMA), ionomycin or phytohemagglutinin (PHA). Recent validation studies demonstrated IL-9 mRNA induction in primary cultures of T-cells treated with PMA and anti-CD3. Similar testing with PBMCs showed significant IL-13 mRNA induction after 48 hours of treatment with PMA, thymosin and staphylococcal enterotoxin. Cytokine STATE® panels are being constructed according to functional categories such as innate or adaptive immunity to better characterize changes in transcription patterns during an immune response. The HPSA™ gene expression assays offer a rapid and convenient alternative to more cumbersome, expensive methods.
IQ™ Technology: Development of a Universal, Homogeneous Method for High-Throughput Screening of Kinase and Phosphatase Activity
Authors: McCauley Timothy J. , Stanaitis Michael L. , Savage M. , Onken Jessica , Millis Sherri Z.
Published: October 2018

IQ™ Technology is a homogeneous, universal detection platform designed specifically for high-throughput screening of kinases and phosphatases. The technology has been tested in 96- to 384- to 1536-well microplate formats and is ideally suited for automated drug discovery screening systems. IQ™ Technology is a direct, non-competitive assay format that does not require antibodies or radioactive reagents to measure phosphorylation state. Kinase or phosphatase activity is quantitated by direct measurement of the phosphorylation state of fluorophore-labeled peptide substrates. Phosphorylation is measured by the change in fluorescence intensity that occurs when a proprietary iron-containing compound binds specifically to phosphoryl groups on peptides. This change in observed fluorescence is proportional to the extent of phosphorylation of the fluorophore-labeled peptide, because the iron-containing compound quenches the fluorescent emission exclusively on the phosphorylated form of the fluorophore-labeled peptide. The IQ™ Technology provides a universal method that can be used with any peptide sequence.
Solution Phase Synthesis and Workup Using an Integrated Approach
Authors: Wint Lewin T. , Kovacevic Marija , Waters Matt , AutoChem Mettler-Toledo
Published: October 2018

Traditional organic synthesis is often cumbersome and time consuming. Significant effort by manufacturers of automated systems has been directed at increasing the speed, efficiency, and consistency of performing chemical reactions. To date, the numbers of integrated systems that combine all the relevant steps of compound preparation are few.

Using the five automated systems in tandem can successfully streamline research and development of potential drug candidates. The features of these workstations offer a unique approach for supporting the convenient synthesis and workup of diverse compounds without compromising reagent types or conditions used for synthesis.

This poster details an example of the automated drug discovery approach to high throughput organic synthesis using the solution phase synthesis of a series of 1-indanones as building blocks and subsequent reductive amination reactions to generate a diverse group of amines. The purpose of each automated system is outlined along with its role in generating the small library as an illustration of the importance of time saving devices in laboratories.
A Centralized Laboratory Maintenance Project
Authors: Michienzi Joseph , Weisbein Rober , Cahill Patrick B. , Doucette-Stamm Lynn , Ho Tay , O'Connell Jim , Tsolas Jason , Benn James , Kana Arnie
Published: October 2018

Genome Therapeutics Corp. has implemented a unique maintenance approach for their GenomeVision™ Services 24-by-7 high-throughput Sequencing platform that ensures optimal performance and minimum downtime. A network-enabled software program automatically coordinates and tracks all maintenance tasks, and notifies responsible personnel by e-mail of their upcoming maintenance responsibilities. Production personnel perform all internal scheduled instrumentation maintenance, equipment vendors perform purchased service contracts, and a small in-house group responds to emergency situations. Personnel log completed maintenance tasks and request emergency service by means of a network-based interface that results in rapid response of appropriate in-house personnel or outside service organizations. The proprietary software program tracks all maintenance activities for each instrument, enabling upgrades to routine maintenance procedures, identification of opportunities for sequencing platform improvements, and more effective instrumentation purchasing decisions.
ADMET Assays on Tecan's LabCD-ADMET System
Authors: Shea Michelle , Ommert Shari , Gleich Lance , Towle Theresa , Haspel Howard , Schmid Noa , Jindal Hitesh , Kellogg Greg , Carvalho Bruce , Contarino Michael , Bansal Praveen
Published: October 2018

Screening for ADME/Tox properties of compounds is a key step in the drug development process. Three applications defining such properties, namely Cytochrome P450 Inhibition, Serum Protein Binding and P-glycoprotein Interaction were developed and the performance of each was evaluated on Tecan's LabCD-ADMET System. The LabCD-ADMET System is an automated platform which integrates microfluidics, in the form of the centrifugally driven LabCD device; liquid handling and assay robotics, in the form of a modified GENESIS liquid handling workstation; an incubation, spinner, and detection system, the ULTRA LabCD; and platform/application-specific software. The assay approach and the data for each application are presented. Two applications, Cytochrome P450 inhibition and serum protein binding assays, have also been externally validated at leading pharmaceutical companies within Tecan's Early Access Program (EAP). The LabCD-ADMET System provides a miniaturized, integrated, and automated turnkey solution for various ADME/Tox applications.
A Study of a High-Throughput Plasmid DNA Purification System
Authors: James Alexander T. , Wu Joanna , Braunthal Nelson , Azarani Arezou , Discoveries Apogent
Published: October 2018

An automated process that incorporates Millipore's Plasmid Miniprep96 Montáge™ Kit with the Apogent Discoveries PlateMate Plus® and Tango™ automated high-throughput dispensing systems has been developed for purifying plasmid DNA. To test the efficacy of this process, parameters such as the reproducibility and consistency of the purified DNA quantity and quality as well as the purification speed were analyzed. The purification time for two plates of the Plasmid Miniprep96 Kit (192 samples) was approximately 60 minutes using a PlateMate Plus equipped with 96 disposable tips and the Tango system equipped with 96 RB (resin bead) syringes. High uniformity and consistency in DNA yields (determined by spectrophotometric analysis) and quality (determined by gel electrophoresis analysis) among the different wells were observed. The purified plasmid DNA samples sequenced at an exceptional level with an average PHRED Q> 20 of 819 ± 25.
Automated Purification of Transfection-Grade Plasmid DNA Using Wizard MagneSil Tfx System
Authors: White Douglas , Creswell Donald , Schenborn Elaine , Krueger Steve
Published: October 2018

We describe a reagent system and robotic protocol for the isolation of highly purified plasmid DNA from cultured cells. The method is based on the Wizard® MagneSil™ Plasmid Purification System, which purifies sequencing-grade plasmid DNA. Two modifications to the sequencing-grade system were made to create the Wizard MagneSil Tfx™ System. This system provides lower endotoxin and other contaminant levels, giving higher quality plasmid for transfection applications. The Wizard MagneSil Tfx™ System uses MagneSil™ Paramagnetic Particles (PMPs) to clear lysate and bind plasmid, eliminating the need for filtration devices. The endotoxin removal step uses MagneSil™ (PMPs) and a guanidine/isopropanol wash to remove RNA and protein. One 96-well plate may be processed in 45 minutes on the Beckman Biomek® FX robotic workstation. We provide data showing DNA yield, contaminant levels, and transfection efficiency for 5 commonly used cell lines. Comparisons with other systems are also shown.
Automation of In Vitro Dose-Inhibition Assays Utilizing the Tecan Genesis and an Integrated Software Package to Support the Drug Discovery Process
Authors: Mosser Scott D. , Gaul Stanley L. , Bednar Bohumil , Koblan Kenneth S. , Bednar Rodney A. , Bednar Rodney A.
Published: October 2018

We have automated in vitro dose-inhibition assays to evaluate newly synthesized chemical entities and to rapidly produce and disseminate the results with minimal personnel. A variety of assay methods were automated using the Tecan Genesis Workstation to produce ten-point titration curves and generate reproducible KI values. Our integrated software package provides the unique ability to simultaneously inventory and schedule compounds into various in vitro assays. A worklist generator, in combination with a Gemini script automatically makes variable pre-dilutions of compounds, retrieves incubation plates from the Carousel using the RoMa Arm, performs serial dilutions of compounds within the final 96 well incubation plate using disposable tips, and adds essential assay reagents. Our “Expert System for Data Analysis” automatically retrieves data from a reader (e.g. TopCount, FLIPR or VIPR), analyzes the data based on a set of rules, and provides value added reports. An overview of the basic workflow and the integrated software for support of the drug discovery process is described. The ability of the Tecan Robot to produce dose-inhibition profiles is illustrated and validated by using a radioligand binding assay and a DMSO solubilized fluorescein dye method.
The inseparability of sampling and time and its influence on attempts to unify the molecular and fossil records
Authors: Hopkins Melanie J. , Bapst David W. , Simpson Carl , Warnock Rachel C. M.
Published: October 2018

The two major approaches to studying macroevolution in deep time are the fossil record and reconstructed relationships among extant taxa from molecular data. Results based on one approach sometimes conflict with those based on the other, with inconsistencies often attributed to inherent flaws of one (or the other) data source. Any contradiction between the molecular and fossil records represents a failure of our ability to understand the imperfections of our data, as both are limited reflections of the same evolutionary history. We therefore need to develop conceptual and mathematical models that jointly explain our observations in both records. Fortunately, the different limitations of each record provide an opportunity to test or calibrate the other, and new methodological developments leverage both records simultaneously. However, we must reckon with the distinct relationships between sampling and time in the fossil record and molecular phylogenies. These differences impact our recognition of baselines and the analytical incorporation of age estimate uncertainty.
Selective Dating of Paint Components: Radiocarbon Dating of Lead White Pigment
Authors: Hendriks Laura , Hajdas Irka , Ferreira Ester S B , Scherrer Nadim C , Zumbühl Stefan , Küffner Markus , Carlyle Leslie , Synal Hans-Arno , Günther Detlef
Published: October 2018

Lead white is a man-made white pigment commonly used in works of art. In this study, the possibility of radiocarbon dating lead white pigments alone and in oil paints was explored using well-dated lead white pigments and paints. Resulting14C ages on lead white pigments produced following the traditional stack process, where carbonate groups results from the incorporation of CO2originating from fermentation, matched the production years, while radiocarbon dating of lead white made using other industrial processes indicate that14C depleted CO2was used in their production. The method was applied to two case studies, where lead carbonate samples were dated in two oil paintings, one Baroque and one from the 20th century. We hereby show that the lead white pigment can be dated by14C and used as proxy for the time of creation of an artwork. Additionally, a two-step method was developed to allow14C analysis of both the lead white pigment and oil binder from the same sample. A single lead white paint sample can yield two distinct radiocarbon ages, one from the carbonate and one from the natural organic binder. This study thus proposes new strategies for14C dating of artworks.
Distribution ofα-tocopherol stereoisomers in mink (Mustela vison) organs varies with the amount ofall-rac-α-tocopheryl acetate in the diet
Authors: Hymøller Lone , Lashkari Saman , Clausen Tove N. , Jensen Søren K.
Published: October 2018

Syntheticα-tocopherol has eight isomeric configurations including four 2R (RSS,RRS,RSR,RRR) and four 2S (SRR,SSR,SRS,SSS). Only theRRRstereoisomer is naturally synthesised by plants. A ratio of 1·36:1 in biopotency ofRRR-α-tocopheryl acetate toall-rac-α-tocopheryl acetate is generally accepted; however, studies indicate that neither biopotency ofα-tocopherol stereoisomers nor bioavailability between them is constant, but depend on dose, time, animal species and organs. A total of forty growing young male mink were, after weaning, assigned one of the following treatments for 90 d: noα-tocopherol in diet (ALFA_0), 40 mg/kgRRR-α-tocopheryl acetate (NAT_40), 40 mg/kgall-rac-α-tocopheryl acetate (SYN_40) and 80 mg/kg feedall-rac-α-tocopheryl acetate (SYN_80). Mink were euthanised in CO2and blood was collected by heart puncture. Mink were pelted and liver, heart, lungs, brain and abdominal fat were collected forα-tocopherol stereoisomer analysis. The proportion ofRRR-α-tocopherol decreased in all organs and plasma with increasing amount of syntheticα-tocopherol stereoisomers in the diet (P≤0·05), whereas the proportion of all syntheticα-tocopherol stereoisomers increased with increasing amount of syntheticα-tocopherol stereoisomers in the diet (P≤0·05). The proportion ofα-tocopherol stereoisomers in plasma, brain, heart, lungs and abdominal fat showed the following order:RRR>RRS,RSR,RSS>Σ2S, regardless ofα-tocopherol supplement. The liver had the highest proportion of Σ2Sstereoisomers, and lowest proportion ofRRR-α-tocopherol. In conclusion, distribution ofα-tocopherol stereoisomers differs with dose and form ofα-tocopherol supplementation. The results did also reveal the liver’s role as the major organ for accumulation of Σ2S α-tocopherol stereoisomers.
Is exercise best served on an empty stomach?
Authors: Wallis Gareth A. , Gonzalez Javier T.
Published: October 2018

The objective of this review paper is to evaluate the impact of undertaking aerobic exercise in the overnight-fastedv.fed-state, in the context of optimising the health benefits of regular physical activity. Conducting a single bout of aerobic exercise in the overnight-fastedv.fed-state can differentially modulate the aspects of metabolism and energy balance behaviours. This includes, but is not limited to, increased utilisation of fat as a fuel source, improved plasma lipid profiles, enhanced activation of molecular signalling pathways related to fuel metabolism in skeletal muscle and adipose tissue, and reductions in energy intake over the course of a day. The impact of a single bout of overnight-fastedv.fed-state exercise on short-term glycaemic control is variable, being affected by the experimental conditions, the time frame of measurement and possibly the subject population studied. The health response to undertaking overnight-fastedv.fed-state exercise for a sustained period of time in the form of exercise training is less clear, due to a limited number of studies. From the extant literature, there is evidence that overnight-fasted exercise in young, healthy men can enhance training-induced adaptations in skeletal muscle metabolic profile, and mitigate against the negative consequences of short-term excess energy intake on glucose tolerance compared with exercising in the fed-state. Nonetheless, further long-term studies are required, particularly in populations at-risk or living with cardio-metabolic disease to elucidate if feeding status prior to exercise modulates metabolism or energy balance behaviours to an extent that could impact upon the health or therapeutic benefits of exercise.
Shifted baselines and the policy placebo effect in conservation
Authors: Lovell Samantha , Johnson Ayana Elizabeth , Ramdeen Robin , McClenachan Loren
Published: October 2018

Coastal ecosystems have been degraded by human activity over centuries, with loss of memory about past states resulting in shifted baselines. More recently conservation efforts have resulted in localized recoveries of species and ecosystems. Given the dynamism of ecosystem degradation and recovery, understanding how communities perceive long-term and recent changes is important for developing and implementing conservation measures. We interviewed stakeholders on three Caribbean islands and identified a shifted baseline with respect to the extent and degree of long-term declines in marine animal populations; stakeholders with more experience identified more species as depleted and key species as less abundant than those with less experience. Notably, the average respondent with < 15 years of experience listed no species as depleted despite clear evidence of declines. We also identified a phenomenon we call the policy placebo effect, in which interviewees perceived some animal populations as recently recovering following passage of new conservation legislation but in the absence of evidence for actual recovery. Although shifted baselines have a negative effect on conservation as they can lower recovery goals, the outcomes of a policy placebo effect are unclear. If the public prematurely perceives recovery, motivation for continued conservation could decline. Alternatively, perception of rapid success could lead communities to set more ambitious conservation goals.
Neurococognitive and neuroimaging correlates of obesity and components of metabolic syndrome in bipolar disorder: a systematic review
Authors: Bora Emre , McIntyre Roger S. , Ozerdem Aysegul
Published: October 2018

Background

Individuals with bipolar disorder (BD) have a higher prevalence of obesity and metabolic syndrome (MetS) compared with the general population. Obesity and MetS are associated with cognitive deficits and brain imaging abnormalities in the general population. Obesity and components of MetS might potentially associate with neuroimaging and neurocognitive findings in BD.

Methods

A literature search of studies investigating the association between obesity (and other components of MetS) and neurocognitive and neuroimaging findings in BD was conducted. In addition to a systematic review, a random-effects meta-analysis was conducted when sufficient data were available.

Results

Twenty-three studies were included in the current systematic review. Overweight/obese patients were significantly associated with impaired neurocognition compared normal weight individuals with BD (d= 0.37). The most robust association between obesity and cognitive deficits in BD was observed in the cognitive subdomain of executive functions (d= 0.61). There was also evidence for a significant relationship between cognitive impairment in BD and other components of MetS including hypertension, dyslipidemia, and diabetes. Overweight/obese individuals with BD had more pronounced brain imaging abnormalities than normal weight individuals with BD.

Conclusions

Obesity and related cardiovascular risk factors significantly are associated with more severe cognitive and brain imaging abnormalities in BD. Medical co-morbidities can potentially contribute to functional decline observed in some patients throughout the course of BD.
TESTING GARCH-X TYPE MODELS
Authors: Pedersen Rasmus Søndergaard , Rahbek Anders
Published: October 2018

We present novel theory for testing for reduction of GARCH-X type models with an exogenous (X) covariate to standard GARCH type models. To deal with the problems of potential nuisance parameters on the boundary of the parameter space as well as lack of identification under the null, we exploit a noticeable property of specific zero-entries in the inverse information of the GARCH-X type models. Specifically, we consider sequential testing based on two likelihood ratio tests and as demonstrated the structure of the inverse information implies that the proposed test neither depends on whether the nuisance parameters lie on the boundary of the parameter space, nor on lack of identification. Asymptotic theory is derived essentially under stationarity and ergodicity, coupled with a regularity assumption on the exogenous covariate X. Our general results on GARCH-X type models are applied to Gaussian based GARCH-X models, GARCH-X models with Student’s t-distributed innovations as well as integer-valued GARCH-X (PAR-X) models.
Prosody perception and production by children with cochlear implants
Authors: VAN DE VELDE Daan J. , SCHILLER Niels O. , LEVELT Claartje C. , VAN HEUVEN Vincent J. , BEERS Mieke , BRIAIRE Jeroen J. , FRIJNS Johan H. M.
Published: October 2018

The perception and production of emotional and linguistic (focus) prosody were compared in children with cochlear implants (CI) and normally hearing (NH) peers. Thirteen CI and thirteen hearing-age-matched school-aged NH children were tested, as baseline, on non-verbal emotion understanding, non-word repetition, and stimulus identification and naming. Main tests were verbal emotion discrimination, verbal focus position discrimination, acted emotion production, and focus production. Productions were evaluated by NH adult Dutch listeners. All scores between groups were comparable, except a lower score for the CI group for non-word repetition. Emotional prosody perception and production scores correlated weakly for CI children but were uncorrelated for NH children. In general, hearing age weakly predicted emotion production but not perception. Non-verbal emotional (but not linguistic) understanding predicted CI children's (but not controls’) emotion perception and production. In conclusion, increasing time in sound might facilitate vocal emotional expression, possibly requiring independently maturing emotion perception skills.
Zinder 1906, histoires d'un complot: Penser le moment de l'occupation coloniale
Authors: Lefebvre Camille
Published: October 2018

À travers l'histoire de ce que les colonisateurs français ont considéré comme un complot contre leur présence, cet article reconstitue la complexité des premiers temps de l'occupation coloniale dans la région de Zinder (Niger) au début du xxe siècle. Trois types de sources, correspondant à la fois à trois moments successifs et à trois regards sur l’événement, sont tour à tour déployés : les archives de l'enquête coloniale constituées par les militaires qui l'ont menée pour justifier leur action ; les journaux personnels et les notes privées de l'interprète du poste, Moïse Landeroin, qui ne croit pas à la culpabilité des accusés et s'oppose à ses supérieurs ; enfin, les lettres en arabe écrites par l'un des accusés, Malam Yaro, pour plaider son innocence. Cette dernière source permet de relire l’événement en révélant les enjeux sociaux à l’œuvre au sein de la société de Zinder de l’époque. La diversité des documents permet ainsi de reconstituer les différentes temporalités qui nourrissent ce moment et de révéler les points aveugles d'une lecture uniquement coloniale de l’événement.
Le passé mis en pièce(s): Archives, conflits et droits de cité à Alger, 1830-1870
Authors: Grangaud Isabelle
Published: October 2018

Enquêter sur les processus de destruction du patrimoine cultuel algérois au cours des trente premières années de la conquête française de l'Algérie nous amène, en prêtant attention à la genèse de leur production, à considérer deux sources qui renvoient à une période antérieure à la conquête : Les édifices religieux de l'ancien Alger d'Albert Devoulx et le « Fonds ottoman », dont l'archivage fut initialement mis en œuvre par celui-ci. Ce double travail archéologique mené à partir de la reconstitution des activités d'A. Devoulx conduit à la mise au jour d'une lutte virulente pour les droits de cité et, notamment, pour l'appropriation des fondations pieuses des institutions dévotionnelles de la ville, une bataille dont ces sources furent partie prenante. En prêtant attention à leur charge revendicative et à la nature de leurs interactions, il devient possible de retracer l'histoire de la fin des mosquées d'Alger et d'apprécier, dans le même temps, la nature véritable de ces sources.
Expliquer la modernisation économique allemande: La Révolution française, les réformes prussiennes et l'inévitable continuité du changement
Authors: Kopsidis Michael , Bromley Daniel W.
Published: October 2018

Le cheminement de l'Allemagne vers l'industrialisation, qui dura plusieurs siècles, doit être compris comme une évolution institutionnelle graduelle qui bénéficia des circonstances et fut une réponse aux pénuries de la fin du xviiie siècle. Les tentatives pour lui trouver un deus ex machina unique – qu'il s'agisse de Napoléon, de réformateurs prussiens ou d'un autre agent exogène – n'ont abouti à aucun résultat convaincant. Le gradualisme explique de manière vraisemblable comment l’économie de marché et le capitalisme se sont implantés dans la société allemande. Seules les régions d'Allemagne qui avaient réussi à lancer des réformes institutionnelles graduelles au xviiie siècle étaient bien placées pour devenir rapidement des économies de marché identifiables au début du xixe siècle. Dans ce contexte, cet article se propose d’étudier le rôle de la Prusse et de Napoléon dans la modernisation de la structure institutionnelle de l’économie allemande. En matière de réformes agraires et de liberté économique, le modèle prussien représente un bouleversement dans l'histoire du développement économique. Une telle stratégie n'existait dans aucun territoire sous domination française, que ce soit avant ou après 1815. Les réformateurs prussiens furent les premiers à adopter une stratégie de développement rural multisectoriel qui leur permit de concilier croissance et équité.
On Erdős–Ko–Rado for Random Hypergraphs II
Authors: HAMM A. , KAHN J.
Published: October 2018

Denote by${\mathcal H}_k$(n,p) the randomk-graph in which eachk-subset of {1,. . .,n} is present with probabilityp, independent of other choices. More or less answering a question of Balogh, Bohman and Mubayi, we show: there is a fixed ε > 0 such that ifn= 2k+ 1 andp> 1 - ε, then w.h.p. (that is, with probability tending to 1 ask→ ∞),${\mathcal H}_k$(n,p) has the ‘Erdős–Ko–Rado property’. We also mention a similar random version of Sperner's theorem.
First-Surface Scintillator for Low Accelerating Voltage Scanning Electron Microscopy (SEM) Imaging
Authors: Tzolov Marian B. , Barbi Nicholas C. , Bowser Christopher T. , Healy Owen
Published: October 2018

Highly luminescent thin films of zinc tungstate (ZT) have been deposited on top of conventional scintillators (Yttrium Aluminum Perovskite, Yttrium Aluminum Garnet) for electron detection in order to replace the need for a top conducting layer, such as indium tin oxide (ITO) or aluminum, which is non-scintillating and electron absorbing. Such conventional conducting layers serve the single purpose of eliminating electrical charge build-up on the scintillator. The ZT film also eliminates charging, which has been verified by measuring the Duane–Hunt limit and electron emission versus accelerating voltage. The luminescent nature of the ZT film ensures effective detection of low energy electrons from the very top surface of the structure ZT/scintillator, which we call “first-surfacescintillator”. The cathodoluminescence has been measured directly with a photodetector and spectrally resolved at different accelerating voltages. All results demonstrate the extended range of operation of the first-surface scintillator, while the conventional scintillators with a top ITO layer decline below 5 kV and have practically no output below 2 kV. Scintillators of different types were integrated in a detection system for backscattered electrons (BSE). The quality of the image at high accelerating voltages is comparable with the conventional scintillator and commercial BSE detector, while the image quality at 1 kV from the first-surface scintillator is superior.
Extracting Grain Orientations from EBSD Patterns of Polycrystalline Materials Using Convolutional Neural Networks
Authors: Jha Dipendra , Singh Saransh , Al-Bahrani Reda , Liao Wei-keng , Choudhary Alok , De Graef Marc , Agrawal Ankit
Published: October 2018

We present a deep learning approach to the indexing of electron backscatter diffraction (EBSD) patterns. We design and implement a deep convolutional neural network architecture to predict crystal orientation from the EBSD patterns. We design a differentiable approximation to the disorientation function between the predicted crystal orientation and the ground truth; the deep learning model optimizes for the mean disorientation error between the predicted crystal orientation and the ground truth using stochastic gradient descent. The deep learning model is trained using 374,852 EBSD patterns of polycrystalline nickel from simulation and evaluated using 1,000 experimental EBSD patterns of polycrystalline nickel. The deep learning model results in a mean disorientation error of 0.548° compared to 0.652° using dictionary based indexing.
Ozone Treatment of Grapes During Withering for Amarone Wine: A Multimodal Imaging and Spectroscopic Analysis
Authors: Cisterna Barbara , Boschi Federico , Croce Anna C. , Podda Rachele , Zanzoni Serena , Degl’Innocenti Daniele , Bernardi Paolo , Costanzo Manuela , Marzola Pasquina , Covi Viviana , Tabaracci Gabriele , Malatesta Manuela
Published: October 2018

The production of Amarone wine is governed by a disciplinary guideline to preserve its typical features; however, postharvest infections by the fungusBotrytis cinerea(B. cinerea) not only represent a phytosanitary problem but also cause a significant loss of product. In this study, we tested a treatment with mild ozoniztion on grapes for Amarone wine production during withering in thefruttaio(the environment imposed by the disciplinary guideline) and evaluated the impact on berry features by a multimodal imaging approach. The results indicate that short and repeated treatments with low O3concentrations speed up the naturally occurring berry withering, probably inducing a reorganization of the epicuticular wax layer, and inhibit the development ofB. cinerea,blocking the fungus in an intermediate vegetative stage. This pilot study will pave the way to long-term research on Amarone wine obtained from O3-treated grapes.
Development of HP-TLC method for rapid quantification of sugars, catechins, phenolic acids and saponins to assess Yam (Dioscorea spp.) tuber flour quality
Authors: Lebot V. , Malapa R. , Molisalé T.
Published: October 2018

Eight yam species (Dioscorea spp.) represented by 522 accessions (landraces and hybrids) were analysed for the individual sugars, catechins, phenolic acids and saponins contents of their tuber flours. Maltose, sucrose, glucose and fructose were quantified. Reducing sugars mean values were highly variable within species and ranged from 0.16%dry weight (DW) (SD ± 0.12) in D. dumetorum to 3.15%DW (±2.49) in D. esculenta. Maltose was detected only in D. esculenta. Chlorogenic acid, gallic acid and other phenolic acids ranged from 4.33 mg/g DW in D. bulbifera to 4.87 mg/g in D. alata and 9.55 mg/g in D. nummularia but were not detected in other species. Catechins (epicatechin and catechin) were highest in D. bulbifera bulbils (25.18 mg/g) and tubers (6.96 mg/g), and lowest in D. esculenta (0.32 mg/g). Their content is significantly correlated with dark flour colour and they most likely contribute to the oxidation of tuber flesh. Saponins (dioscin and gracillin) were quantified in only two species: D. cayenensis (5.94 mg/g, SD ± 3.78) and D. esculenta (3.74 mg/g, SD ± 3.72). Varietal selection may tend to reduce sugars levels and increase secondary metabolites with bioactive properties. HP-TLC is a suitable technique for the rapid quantification of compounds related to yam tuber flour quality.
Renaming schizophrenia: 5 × 5
Authors: Guloksuz Sinan , van Os Jim
Published: October 2018

There had been a long way to go before we felt comfortable about even discussing the issues revolving around the concept of ‘schizophrenia’, let alone reckoning on mere semantic revision. In this editorial, we aim to extend our discussion on the reasons behind the slow death of the concept of ‘schizophrenia’ and the benefits of changing the name and embracing a spectrum approach with an umbrella psychosis spectrum disorder (PSD) category (similar to autism spectrum disorder) that goes further than a mere semantic revision. We attempted to cover the topic of the renaming by providing five most pertinent points categorised under five domains: reasons, signals, challenges, promises and steps for the change. Admittedly, even a modest revision, such as classifying all psychotic disorder categories under an umbrella category of PSD, and abolishing the term schizophrenia requires careful deliberation and some effort in the beginning, but the revision is well worth the effort considering the benefits in the long run. Renaming a particular form of mental suffering should be accompanied by a broader debate of the entire diagnosis-evidence-based-practice (EBP)-symptom-reduction model as the normative factor driving the content and organisation of mental health services that may be detached from patients’ needs and reality, overlooks the trans-syndromal structure of mental difficulties, appraises the significance of the technical features over the relational and ritual components of care, and underestimates the lack of EBP group-to-individual generalisability. Individuals may make great strides in attaining well-being by accommodating to living with mental vulnerabilities through building resilience in the social and existential domains. Changing the name and the concept of ‘schizophrenia’, which goes beyond a mere semantic revision, may become the first step that allows catalysation of the process of modernising psychiatric science and services worldwide.
Method for Analysis of the Effect of Geomagnetic Disturbances on Ultraviolet Airglow Intensity
Authors: Putis M. , Bobik P. , Mackovjak S.
Published: October 2018

Airglow is a dynamic phenomenon which depends on the geographical location, season, local time, geomagnetic activity, and other conditions. Variations in UV nighttime airglow (300–500 nm) caused by magnetospheric disturbances for several selected points around globe are presented in this study. Used airglow intensity data were evaluated in empirical model Atmospheric Ultraviolet Radiance Integrated Code. We focus on points around the auroral oval position for very disturbed magnetosphere (Kp = 8) and positions chosen for the Airglow MONitor network. This network will consist of a set of small one pixel detectors, designed for long time measurements. A simple statistical method was developed for long time data analysis of geomagnetic disturbances of airglow. Results of the method for planned stations are presented.
Seeing Mars in a Grain of Sand
Authors: Lapotre Mathieu
Published: October 2018

The second phase of Curiosity’s campaign at the Bagnold Dunes brought new observations of windblown sands during Mars’s windy season.
S‐Wave Receiver Function Analysis of the Pampean Flat‐Slab Region: Evidence for a Torn Slab
Authors: Haddon A. , Porter R.
Published: October 2018

Flat‐slab subduction is an atypical form of subduction where the downgoing plate assumes a low‐angle or subhorizontal geometry as it descends beneath the overriding plate. These systems have profound impacts on upper‐plate deformation and volcanism, yet there are outstanding questions regarding the causes, initiation, and termination of flat‐slab subduction. The Pampean flat‐slab region, located in the South American Cordillera, is an ideal locale to study the evolution of these systems due to its well‐constrained geologic history and the continuity of subduction along the western margin of the continent. In this work, we utilize S wave receiver functions (SRFs) to measure the thicknesses and geometry of the subducting Nazca plate lithosphere and the overriding South American plate within the region. Results from this study show overthickened Nazca Plate crust (~15–20 km thick) in the flat‐slab region. Prior to the slab steepening, SRFs indicate a velocity increase rather than a decrease at the top of slab crust, which is consistent with a transition from basalt to eclogite within the crust as it dehydrates. Margin parallel cross sections are consistent with differing transitions between flat‐subduction and more‐typical subduction occurring to the north and south. In the north, the transition appears to be gradual, consistent with slab bending. To the south, SRFs indicate an abrupt change, consistent with slab tearing. These differences are consistent with significant variations in slab rheology along the margin, which may reflect differing thermal regimes. This work has global implications for the three‐dimensional effects of flat‐slab subduction.
Structure and Variability of the Martian Ion Composition Boundary Layer
Authors: Halekas J. S. , McFadden J. P. , Brain D. A. , Luhmann J. G. , DiBraccio G. A. , Connerney J. E. P. , Mitchell D. L. , Jakosky B. M.
Published: October 2018

A complex boundary layer with a variety of charged particle and electromagnetic field signatures, including a transition between plasma predominantly of solar wind origin and plasma of planetary origin, lies between the Martian bow shock and the ionosphere. In this paper, we develop and utilize algorithms to autonomously identify and characterize this ion composition boundary (ICB), using data from the Mars Atmosphere and Volatile EvolutioN mission. We find an asymmetric ICB with a larger average thickness, lower altitude, and lower velocity shear in the hemisphere where the solar wind motional electric field points outward, as a result of the asymmetry of the mass loading process. The ICB thickness scales with the magnetosheath proton gyroradius at the top of the boundary layer but does not clearly vary with external drivers. The ICB location varies with solar wind ram pressure and crustal magnetic field strength, but does not clearly respond to solar wind Mach number or extreme ultraviolet irradiance. The ICB represents a distinct boundary for ion density and flow speed, but the magnetic field strength and direction typically do not vary significantly across the ICB. The plasma density and flow speed at the ICB vary seasonally, likely in response to variations in the neutral exosphere and/or atmosphere. However, the ICB on average remains at or below the altitude where pressure balance is achieved between the piled up magnetic field and the solar wind ram pressure, regardless of season or crustal magnetic field strength.
Tidal Mixing Sustains a Bottom‐Trapped River Plume and Buoyant Coastal Current on an Energetic Continental Shelf
Authors: Wu Tianning , Wu Hui
Published: October 2018

Conventional wisdoms on river plume dynamics suggest that a down‐shelf buoyant coastal current will ultimately be trapped at a specific depth, that is, the trapping depth, as constrained by riverine outflow and offshore bottom Ekman transport. Theoretically, a prerequisite down‐shelf current is necessary to form a stable bottom‐trapped river plume. In this study an alternative is described by carrying out a modeling study on the Zhe‐Min Coastal Current (ZMCC). Buoyant water from the Changjiang River is a major factor driving the ZMCC, as is common in bottom‐trapped river plumes; however, the trapping depth is more determined by tidal mixing. When the plume water comes to the sloping topography, strong tidal mixing induces a mixing front, shoreward of which the bottom Ekman layer occupies the entire water column. Such a tidal‐induced front maintains a down‐shelf frontal current, which is intensified both at the surface due to the thermal wind balance and on the top of bottom boundary layer due to the tidal rectification. Direct wind‐induced transport only covers a small fraction of the ZMCC; however, it redistributes the plume water and, thus, affects the coastal current. The tide‐induced frontal trapping depth varies much less between seasons than that predicted by previous plume theories. Instead, it fluctuates strongly in the spring‐neap cycle. Even in summer when upwelling‐favorable winds prevail, the mixing front still sustains a down‐shelf coastal current. Intense tidal mixing exists in many coastal waters, which might be an alternative mechanism in forming bottom‐trapped river plumes and their associated buoyant coastal current.
Prokinetics for Functional Dyspepsia: A Systematic Review and Meta-Analysis of Randomized Control Trials
Authors: Pittayanon Rapat , Yuan Yuhong , Bollegala Natasha P , Khanna Reena , Lacy Brian E. , Andrews Christopher N. , Leontiadis Grigorios I. , Moayyedi Paul
Published: October 2018

OBJECTIVES:

Prokinetics are recommended for the treatment of functional dyspepsia (FD) but systematic reviews give conflicting results on the efficacy of these agents. We have therefore conducted an updated systematic review to support the 2017 joint ACG/CAG dyspepsia guidelines.

METHODS:

Electronic databases, including MEDLINE, EMBASE, and CENTRAL, were searched until September 2017 for randomized controlled trials (RCTs) comparing either prokinetics and placebo or two types of prokinetics to improve FD symptoms. The primary outcome was absence or improvement of dyspeptic symptoms at the end of treatment. Double-blind eligibility assessment and data extraction was performed. Pooled risk ratios of symptoms persisting or adverse events occurring, and standardized mean difference of quality-of-life (QoL) scores with 95% CI, using a random effects model, were calculated. Quality of evidence was assessed using GRADE.

RESULTS:

The search identified 1388 citations; 38 studies in 35 papers were included. Of these, 29 trials comparing prokinetics with placebo were found. There was a statistically significant effect of prokinetic treatment in reducing global symptoms of FD (RR 0.81, 95% CI 0.74 to 0.89; I2 91%; NNT 7), regardless of FD subtype or ethnicity. When comparing two types of prokinetic, the most commonly used comparator was domperidone. There was no difference in reducing global symptoms (RR 0.94, 95% CI 0.83 to 1.07). QoL was not improved with prokinetic treatment. The adverse events with individual prokinetics were not different from placebo, except for cisapride. The GRADE assessment rated the quality of the evidence in each outcome as very low.

CONCLUSIONS:

From the current evidence, prokinetics may be effective for the treatment in all subtypes of FD, with very low quality of evidence. There was no difference between prokinetics for dyspeptic symptom improvement. High-quality RCTs with large sample sizes of FD patients are needed to verify the efficacy of prokinetics.
miR-3178 inhibits cell proliferation and metastasis by targeting Notch1 in triple-negative breast cancer
Authors: Kong Peng , Chen Lie , Yu Muxin , Tao Jing , Liu Jiawei , Wang Yue , Pan Hong , Zhou Wenbin , Wang Shui
Published: October 2018

Triple-negative breast cancer (TNBC) has a poorer outcome than other subtypes of breast cancer, and the discovery of dysregulated microRNA (miRNA) and their role in tumor progression has provided a new avenue for elucidating the mechanism involved in TNBC. In this study, we identified that miR-3178 was significantly reduced in TNBC, and the low miR-3178 expression correlated with poor overall survival in TNBC but not in non-TNBC. The ectopic overexpression of miR-3178 suppressed TNBC cell proliferation, invasion, and migration by inhibiting the epithelial-to-mesenchymal (EMT) transition. Notch1 was validated as the direct target gene of miR-3178, which was confirmed by the dual-luciferase reporter assay. miR-3178 decreased the expression of Notch1 and restoration of Notch1 expression attenuated the inhibitory effects of miR-3178 on cell proliferation, metastasis, and the EMT in TNBC. miR-3178 inhibited cell proliferation and metastasis by targeting Notch1 in TNBC, and the restoration of miR-3178 might be a potential therapeutic strategy for TNBC.
Inhibiting repulsive guidance molecule-a suppresses secondary progression in mouse models of multiple sclerosis
Authors: Tanabe Shogo , Fujita Yuki , Ikuma Kaori , Yamashita Toshihide
Published: October 2018

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that is characterized by motor deficits, fatigue, pain, cognitive impairment, and sensory and visual dysfunction. Secondary progressive multiple sclerosis (SPMS) is a progressive form of MS that develops from relapsing-remitting MS. Repulsive guidance molecule-a (RGMa) has diverse functions, including axon growth inhibition and immune regulation. Here, we show inhibiting RGMa had therapeutic effects in mouse models of SPMS. We induced experimental autoimmune encephalomyelitis in nonobese diabetic mice (NOD-EAE mice) and treated them with humanized anti-RGMa monoclonal antibody. This treatment significantly suppressed secondary progression of disease and inflammation, demyelination and axonal degeneration. In addition, treatment with anti-RGMa antibody promoted the growth of corticospinal tracts and motor recovery in targeted EAE mice with inflammatory lesions in the spinal cord. Collectively, these results show that a humanized anti-RGMa antibody has therapeutic effects in mouse models of SPMS.
BTK: a two-faced effector in cancer and tumour suppression
Authors: Rada Miran , Barlev Nickolai , Macip Salvador
Published: October 2018

Many genes of the human genome display pleiotropic activity, playing an important role in two or more unrelated pathways. Surprisingly, some of these functions can even be antagonistic, often letting to divergent functional outcomes depending on microenviromental cues and tissue/cell type-dependent parameters. Lately, the Bruton’s tyrosine kinase (BTK) has emerged as one of such pleiotropic genes, with opposing effects in cancer pathways. While it has long been considered oncogenic in the context of B cell malignancies, recent data shows that BTK can also act as a tumour suppressor in other cells, as an essential member of the p53 and p73 responses to damage. Since BTK inhibitors are already being used clinically, it is important to carefully review these new findings in order to fully understand the consequences of blocking BTK activity in all the cells of the organism.