bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Fully Automated Process Using a Magnetic Particle Based Kit for Removal of Dye Terminators from Sequencing Reactions
Authors: Spicer Douglas A. , Booth Lisa R. , Hughes Karin A. , Kaiser Robert J. , Springer Amy L. 
Published: October 2018

Prolinx,® Inc. of Bothell, WA has developed the RapXtract™ 384 Dye Terminator Removal Kit for full automation of DNA sequencing reaction purification. The RapXtract product line is based upon proprietary superparamagnetic particle technology that eliminates the need for centrifugation, vacuum filtration, or modified primers to achieve purification of sequencing reactions. The kit described here is pre-dispensed in a 384-well microtiter plate and run on the TECAN GENESIS Workstation 150 (Tecan U.S. Inc., Research Triangle Park, NC). This system enables rapid purification of up to 384 sequencing reactions in a single run. As the completion of the Human Genome Project nears, it is imperative for biotechnology and pharmaceutical companies to increase throughput of DNA sequencing in order to be competitive in the drug discovery and validation process. The “race to market” requires a shift from standard DNA sequencing processes-including DNA sequencing reaction purification-towards complete walk-away automation for all steps. Existing sequencing reaction purification methods (Table 1) require considerable resources including: plastic and other laboratory consumables; specialized equipment, such as high-speed centrifuges or vacuum filtration apparatus; and labor-intensive protocols requiring large amounts of technician time. As a result, walk-away automation of standard purification methods is difficult and expensive.
Microfluidic Devices Made of Glass
Authors: Freitag A. , Vogel D. , Scholz R. , Dietrich T. R. 
Published: October 2018

Mikroglas is a young, innovative and highly-specialized enterprise, which has special know-how in the development of microstructured glass components. Due to its unique properties, glass plays an important role in the field of microtechnology. Most important for many of these new applications are: • its optical transparency and good fluorescence properties, allowing the user to carry out in-situ-measurements, e.g., to detect products after a chemical reaction directly in the device • its stability at high temperatures so that reactions can be influenced by heating different zones of the device • its chemical resistivity, e.g., to handle aggressive substances • its high electrical resistivity, e.g., to transport liquids by electrophoresis or to carry out electrical measurements • its good biological compatibility which is necessary for medical and biological applications The process of structuring FOTURAN will be described. With this technology different microfluidic devices have been manufactured. The channels have a width and depth of 50 μm up to 1 mm and a length of 20 mm up to 280 mm. Various parameters have been measured, e. g., the heat exchange and transfer coefficient for pure water as a function of the temperature. Also optical and thermal analysis techniques have been used to characterize the fluidic components. The results combined with advanced computational fluidic simulations lead to new solutions for different tasks.
Multistep Solution Phase Synthesis of 1,2-Diarylbenzimidazoles on the Trident™System
Authors: Vo Lanchi , Yun Young K. , Wright Peter , Labadie Jeff , Swienty-Busch Juergen 
Published: October 2018

High throughput parallel organic synthesis is now a common practice in discovery chemistry research. Argonaut's modular reaction cassette technology is aimed at parallel synthesis of focused small molecule libraries. The Trident™ automated platform has been designed to perform high throughput organic synthesis using this modular reaction cassette under truly inert conditions and in a robust, reproducible manner. This enables one to generate high quality libraries of small molecules and to access chemistry not normally amenable to automation. Recently we have introduced a Sample Processing Station (SPS), which enhances the upstream and downstream sample handling capabilities of the Trident™ platform. Enhanced software capabilities also provide the Trident™ synthesizer with powerful reaction development and optimization capabilities. Application of this technology in the synthesis of a small library of 1,2-diarylbenzimidazoles using solution-phase chemistry is presented. A number of product purification and isolation protocols using polymer-bound scavengers are discussed.
Optimizing Reaction Conditions of the NanoOrange® Protein Quantitation Method for Use with Microplate-based Automation
Authors: Silberblatt Sarah , Felder Robin A. , Mifflin Theodore E. 
Published: October 2018

Because of the rapidly expanding need for higher sample throughput in drug discovery, automation of corresponding biochemical analyses is desirable. In particular, automation of protein quantitation is crucial since its results are used extensively. Recently, a single-reagent fluorescent protein quantitation method (NanoOrange®) with attractive performance attributes has become available. While it can potentially be automated with liquid handling workstations, several of this method's reaction parameters need to be optimized. We studied the time and a temperature dependence of the NanoOrange protein quantitation reaction in ninety-six well black microplates using either a temperature-regulated hot block or a microwave oven as heat sources. Fluorescence of the NanoOrange reaction was quantified with a multimode microplate spectral scanner. Time-dependent heating profiles of filled microplates placed on hot blocks at fixed temperatures (45, 55, 65, 75, and 95°C) revealed temperature differences of 4–7°C cooler for the outside wells compared to the inner wells, however the maximum well temperature did not exceed 65°C. Similar time-temperature studies of microwave-heated microplates revealed an equilibrium temperature of 45–49°C that was 10–16°C lower than microplates that were block heated. The bovine serum albumin (BSA): NanoOrange standard curves created using a hot block increased in slope from 45°C to 55°C, but then remained constant from 65 to 85°C. Fluorescence of the BSA: NanoOrange standard curve created using a microwave oven was about half the magnitude of the hot block-derived curves, possible reflecting a lower energy transfer rate of the microwave oven. We conclude that the NanoOrange protein quantitation method can be automated if a microplate-compatible hot block with a 65–85°C surface can heat the microplate for minimum of 15 min prior to quantifying the reaction's fluorescence.
Transferring Industrial Automation Technology to the Laboratory
Authors: Harding David , Bradford David , Brown Gavin 
Published: October 2018

Over the past few years, there has been much discussion about transferring industrial technology to laboratories. While it is easy to look at the superficial similarities, it is more important to examine the different requirements of different industries. In this way, it is possible to identify the technologies and techniques that can be successfully transferred to the laboratory to improve performance. This paper takes three very different industries — the bakery, High Throughput Screening (HTS) and mobile phone assembly and examines their different requirements. These industries have been selected from among the many sectors where the RTS Group operates — thus allowing real data from a number of situations to be used. One of the most important areas in automation design is the relationship between flexibility and throughput. This paper focuses on this relationship and its influence over machine configuration when comparing the requirements of the different industries.
Design and Analysis of Microcantilevers for Biosensing Applications
Authors: Zhang Xuan , Yang Mo , Vafai Kambiz , Ozkan Cengiz S. 
Published: October 2018

We have analyzed the detection of microcantilevers utilized in biosensing chips. First, the primary deflection due to the chemical reaction between the analyte molecules and the receptor coating, which produces surface stresses on the receptor side is analyzed. Oscillating flow conditions, which are the main source of turbulence in cantilever based biosensing chips, are found to produce substantial deflections in the microcantilever at relatively large frequency of turbulence. Then mechanical design and optimization of piezoresistive cantilevers for biosensing applications is studied. Models are described for predicting the static behavior of cantilevers with elastic and piezoresistive layers. Chemo-mechanical binding forces have been analyzed to understand issues of saturation over the cantilever surface. Furthermore, the introduction of stress concentration regions during cantilever fabrication has been discussed which greatly enhances the detection sensitivity through increased surface stress, and novel microcantilever assemblies are presented for the first time that can increase the deflection due to chemical reaction. Finally an experiment was made to demonstrate the shift of resonant frequency of cantilever used as biosensor. The relation between resonant frequency shift and the surface stress was analyzed.
Frasnian (Upper Devonian) integrated facies analysis, magnetic susceptibility and sea-level fluctuations in the NW Algerian Sahara
Authors: Mahboubi Abdessamed , Cornée Jean-Jacques , Feist Raimund , Camps Pierre , Girard Catherine 
Published: October 2018

AbstractChanges in the palaeoenvironment are investigated in two representative Frasnian sections of the NW Algerian Sahara, integrating sedimentology and magnetic susceptibility (MS). The Ben Zireg section is characterized by condensed and ferruginous calcareous deposits; in the South Marhouma section the sedimentation rate is high, dominated by muddy nodular limestones with several hypoxic shale intervals. In both sections, sediments were mostly emplaced on pelagic outer ramps below the limit of storm wave-base, evolving through time from proximal to distal setting. Investigations of the temporal evolution of facies and MS data permit a first estimate of the local sea-level trends in NW Algeria. These trends match the overall long-term rise of sea level recognized worldwide from Frasnian Zone 5 upwards. Noteable positive excursions of the sea-level curve related to the semichatovae transgression, as well as to the late Frasnian transgression prior to the late Kellwasser event, can be established in this area. Although the sharp regression of sea level at the upper Kellwasser level can be confirmed from our data, no particular trend is depicted at the transition of conodont zones (Frasnian Zones 12–13) where the presence of the lower Kellwasser level has not yet been clearly recognized.
IS THE EUNETHTA HTA CORE MODEL® FIT FOR PURPOSE? EVALUATION FROM AN INDUSTRY PERSPECTIVE
Authors: Gyldmark Marlene , Lampe Kristian , Ruof Jörg , Pöhlmann Johannes , Hebborn Ansgar , Kristensen Finn Børlum 
Published: October 2018

Objectives:The HTA Core Model® was developed to improve the transferability of health technology assessment (HTA) between settings. The model has been used by HTA agencies but is also of interest to manufacturers, for improving internal evidence generation and communicating with other HTA stakeholders. To establish if the model is fit for purpose from an industry perspective, the pharmaceutical company Roche, collaborating with the European Network for HTA (EUnetHTA), conducted an assessment of the model.Methods:A questionnaire was developed to evaluate all assessment elements in the HTA Core Model v2.0 for their usefulness in meeting payers’ evidence needs and demonstrating value. The questionnaire was completed by country affiliate teams working in evidence generation and reimbursement submissions for pharmaceuticals. Survey results were discussed in workshops to ensure consistency and alignment between teams.Results:The questionnaire was completed by six teams. An additional team from global pricing and market access participated in workshops. Model domains pertaining to the health problem and current technology use, technology description, clinical effectiveness, and economic value were considered most important because they meet payers’ evidence needs. Overall, the model was considered useful to improve the efficiency of HTA evidence generation, share evidence internally, and communicate value to payers and HTA agencies.Conclusions:From an industry perspective, the HTA Core Model provides a useful framework and common terminology for efficient generation of transferable HTA evidence. The timeliness, efficiency, and transparency of HTA processes could be improved by a more standardized approach to HTA across settings.
Une succession d'empires: Les historicités d'une société maghrébine (1860-1930)
Authors: Oualdi M'hamed 
Published: October 2018

RésuméEn étudiant un conflit juridique transméditerranéen autour de la succession d'un ancien ministre tunisien mort à Florence en 1887, cet article appelle à une écriture de l'histoire du Maghreb contemporain qui ne soit pas seulement conçue à partir de l’étude des sources coloniales européennes ou selon une temporalité coloniale mais qui puisse emprunter d'autres cadres d'analyse. Il s'agit aussi de prendre en compte le chevauchement des temporalités impériales française et ottomane en Méditerranée jusqu'aux années 1920, ainsi que la multiplication des litiges nés avant la colonisation de la Tunisie, des dissensions qui continuaient à fournir des raisons d'agir durant la période coloniale. Reconsidérer ces conflits non pas à l'aune de la colonisation mais selon leurs multiples temporalités et en diversifiant les sources nuancerait largement l'idée d'une absence de sources dites « locales » souvent avancée dans les études d'histoire coloniale du Maghreb. Tout autant que les parties prenantes européennes, les acteurs maghrébins impliqués dans des litiges juridiques furent à l'origine d'une profusion documentaire. Ils n'ont cessé de produire des preuves écrites et des justifications – y compris littéraires – en langue arabe pour appuyer leurs argumentaires. Les archives coloniales n'ont capté qu'une partie de ces écrits et donc des sources disponibles pour raconter une autre histoire contemporaine du Maghreb.
Simulation of Legionnaires’ disease prospective spatiotemporal cluster detection, Allegheny County, Pennsylvania, USA
Authors: Orkis L. T. , Peterson E. R. , Brooks M. M. , Mertz K. J. , Harrison L. H. , Stout J. E. , Greene S. K. 
Published: October 2018

AbstractLegionnaires’ disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014–2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.
Effects of Bilingualism on Verbal and Nonverbal Memory Measures in Mild Cognitive Impairment
Authors: Rosselli Mónica , Loewenstein David A. , Curiel Rosie E. , Penate Ailyn , Torres Valeria L. , Lang Merike , Greig Maria T. , Barker William W. , Duara Ranjan 
Published: October 2018

AbstractObjectives:Maintaining two active languages may increase cognitive and brain reserve among bilingual individuals. We explored whether such a neuroprotective effect was manifested in the performance of memory tests for participants with amnestic mild cognitive impairment (aMCI).Methods:We compared 42 bilinguals to 25 monolinguals on verbal and nonverbal memory tests. We used: (a) the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), a sensitive test that taps into proactive, retroactive, and recovery from proactive semantic interference (verbal memory), and (b) the Benson Figure delayed recall (nonverbal memory). A subsample had volumetric MRI scans.Results:The bilingual group significantly outperformed the monolingual group on two LASSI-L cued recall measures (Cued A2 and Cued B2). A measure of maximum learning (Cued A2) showed a correlation with the volume of the left hippocampus in the bilingual group only. Cued B2 recall (sensitive to recovery from proactive semantic interference) was correlated with the volume of the hippocampus and the entorhinal cortex of both cerebral hemispheres in the bilingual group, as well as with the left and right hippocampus in the monolingual group. The memory advantage in bilinguals on these measures was associated with higher inhibitory control as measured by the Stroop Color-Word test.Conclusions:Our results demonstrated a superior performance of aMCI bilinguals over aMCI monolinguals on selected verbal memory tasks. This advantage was not observed in nonverbal memory. Superior memory performance of bilinguals over monolinguals suggests that bilinguals develop a different and perhaps more efficient semantic association system that influences verbal recall. (JINS, 2019, 25, 15–28)
Association between dietary intake and inflammatory markers: results from the CoLaus study
Authors: Piccand Eva , Vollenweider Peter , Guessous Idris , Marques-Vidal Pedro 
Published: October 2018

AbstractObjectiveTo assess the associations between single foods, nutrients, dietary patterns and dietary scores, and inflammatory markers (C-reactive protein (CRP), IL-6, TNF-α and leucocyte count).DesignCross-sectional, population-based study.SettingCity of Lausanne, Switzerland, years 2009–2012.SubjectsAdults (n4027; 46·5 % men), mean age 57·2 (sd10·2) years. Dietary intake was collected using a semi-quantitative FFQ. Single foods and nutrients, three dietary patterns (‘Meat & fries’; ‘Fruits & vegetables’; ‘Fatty & sugary’) and three dietary scores (two Mediterranean; Alternative Healthy Eating Index (AHEI)) were used. Associations were assessed using correlation and multivariable linear regression.ResultsAfter adjusting for total energy intake, gender and other sociodemographic factors, no individual macro- or micronutrient was associated with inflammatory markers. Among single foods, only fruit intake was negatively associated with CRP levels (standardized regression score=−0·043,P<0·01). The ‘Fruits & vegetables’ pattern, the Mediterranean and the AHEI scores were negatively associated with CRP levels (standardized regression score=−0·079, −0·043 and −0·067, respectively, allP<0·01). When entered simultaneously with fruit intake, the ‘Fruits & vegetables’ pattern, the Mediterranean and the AHEI scores tended to remain significantly and negatively associated with CRP levels, while the association with fruit intake was no longer significant. No association between all dietary markers and IL-6, TNF-α or leucocyte count was found.ConclusionsDietary scores, but not individual foods, are associated with inflammatory markers in the general population.
Weight estimation among multi-racial/ethnic infants and children aged 0–5·9 years in the USA: simple tools for a critical measure
Authors: Zhu Yeyi , Hernandez Ladia M , Dong Yongquan , Himes John H , Caulfield Laura E , Kerver Jean M , Arab Lenore , Voss Paula , Hirschfeld Steven , Forman Michele R 
Published: October 2018

AbstractObjectiveIn resource-constrained facilities or during resuscitation, immediate paediatric weight estimation remains a fundamental challenge. We aimed to develop and validate weight estimation models based on ulna length and forearm width and circumference measured by simple and portable tools; and to compare them against previous methods (advanced paediatric life support (APLS), Theron and Traub–Johnson formulas).DesignCross-sectional analysis of anthropometric measurements. Four ulna- and forearm-based weight estimation models were developed in the training set (n 1016). Assessment of bias, precision and accuracy was examined in the validation set (n 457).SettingNational Children’s Study-Formative Research in Anthropometry (2011–2012).SubjectsMulti-racial/ethnic infants and children aged <6 years (n 1473).ResultsDeveloped Models 1–4 had high predictive precision (R2=0·91–0·97). Mean percentage errors between predicted and measured weight were significantly smaller across the developed models (0·1–0·7 %) v. the APLS, Theron and Traub–Johnson formulas (−1·7, 9·2 and −4·9 %, respectively). Root-mean-squared percentage error was overall smaller among Models 1–4 v. the three existing methods (range=7·5–8·7 v. 9·8–13·3 %). Further, Models 1–4 were within 10 and 20 % of actual weight in 72–87 and 95–99 % of the weight estimations, respectively, which outperformed any of the three existing methods.ConclusionsUlna length, forearm width and forearm circumference by simple and portable tools could serve as valid and reliable surrogate measures of weight among infants and children aged <6 years with improved precision over the existing age- or length-based methods. Further validation of these models in physically impaired or non-ambulatory children is warranted.
Ultrastructural Analysis of Vesicular Transport in Electrotransfection
Authors: Wang Liangli , Miller Sara E. , Yuan Fan 
Published: October 2018

AbstractEmerging evidence from various studies indicates that plasmid DNA (pDNA) is internalized by cells through an endocytosis-like process when it is used for electrotransfection. To provide morphological evidence of the process, we investigated ultrastructures in cells that were associated with the electrotransfected pDNA, using immunoelectron microscopy. The results demonstrate that four endocytic pathways are involved in the uptake of the pDNA, including caveolae- and clathrin-mediated endocytosis, macropinocytosis, and the clathrin-independent carrier/glycosylphosphatidylinositol-anchored protein-enriched early endosomal compartment (CLIC/GEEC) pathway. Among them, macropinocytosis is the most common pathway utilized by cells having various pDNA uptake capacities, and the CLIC/GEEC pathway is observed primarily in human umbilical vein endothelial cells. Quantitatively, the endocytic pathways are more active in easy-to-transfect cells than in hard-to-transfect ones. Taken together, our data provide ultrastructural evidence showing that endocytosis plays an important role in cellular uptake and intracellular transport of electrotransfected pDNA.