bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Liquid-Handling Precision with Neptune Software on a Tecan Genesis
Authors: Vessey Andrew , Porter Gregory
Published: October 2018

The process of optimizing the precision of robotic liquid-handling instruments can be improved using the Design of Experiments methodology. Design of Experiments (DOE) is “a collection of statistical and mathematical techniques useful for developing, improving, and optimizing processes.” Using DOE one can design and analyze experiments with the goal of optimizing the precision of liquid deliveries. Tecan has developed a software application, “Neptune” to automate this process for the Tecan Genesis series of instruments. This application has been used to perform experiments on the liquid-handling properties of a variety of liquids. As an example of this process, we will examine a set of experiments performed on a 50% concentration of polyethylene glycol 8000. These experiments resulted in an improvement in the pipetting precision from an average CV of 22.2% to an average of 2.9%.
Standardizing Laboratory Data Interchange in Clinical Trials
Authors: Bassion Susan
Published: October 2018

The Clinical Data Interchange Standards Consortium has developed a Laboratory Model for laboratory data that is generated during the conduct of clinical trials. The Laboratory Model is the first step in proposing standards for the interchange of clinical trial laboratory data. Standards will decrease the time and resources required by stakeholders in the pharmaceutical development process (pharmaceutical companies, biotechnology companies, contract research organizations and laboratories). Standardization will therefore contain costs as well as improve data quality.
High Throughput Methods for Gene Identification, Cloning and Functional Genomics Using the GeneTAC™ G3 Robotics Workstation
Authors: Hamoudi Rifat , Johnston Sally , Hutchinson George , D'Errico John
Published: October 2018

Using a single robotic platform, the GeneTAC™ G3, we have automated most of the processes involved in the cloning and characterisation of novel disease causing genes by addressing the following; firstly, identifying the BACs of interest and making shotgun libraries. Secondly, automating the set up of sequencing reactions using methodology that eliminates the need for DNA preparation of 384 clones. Thirdly, generating sub-libraries using selective re-arraying of library clones to enable the determination of the entire genomic sequence of the gene. Fourthly, determining gene function by combination of differential screening and mini Northerns using microarrays printed using the GeneTAC™ G3 system and hybridised using the GeneTAC™ HybStation (Genomics Solutions, Ann Arbor, USA).
A Flexible and Robust Peer-to-Peer Architecture with XML-Based Open Communication for Laboratory Automation
Authors: McIntosh Roger L. , Yau Alfred
Published: October 2018

Traditional lab automation systems are highly centralized: dispatch and coordination of activities are mediated by a system controller, usually via a single, monolithic control procedure. This approach, while conceptually simple, makes changes to the system difficult; adding or removing instruments and functionality can be a daunting task. In addition, most automated systems are tied to particular development languages and protocols, making operation in heterogeneous environments (i.e., the real world) problematic, since instrument software comes in many different implementations.

We present a peer-to-peer architecture for lab automation, using an XML-based communication protocol. The architecture consists of peer instrument servers, an XML communication layer, and an open control center. Each instrument peer can control, be controlled by, and communicate information to other instrument peers to fulfill the automation task. Our protocol is based on XML-RPC, a lightweight communication standard built atop HTTP. This provides an open and flexible means of peer-to-peer interfacing. The control center serves as a convenient, Web-based interface to manage the instruments. The automated procedure can be distributed across all available instrument peers (each instrument assigned a set of responsibilities); the controller implements a limited set of high-level instructions. The software components included in our prototype system are implemented in various programming languages, including Java, C/C++, Visual Basic, and LabVIEW. Our approach facilitates rapid development of laboratory automation systems.
Centrifugation Based Automated Synthesis Technologies
Authors: Lebl Michal
Published: October 2018

Centrifugation is a powerful method for solid-liquid separation. It can be applied in numerous ways to simplify solid phase synthetic procedures. At the same time, centrifugation is the only totally parallel technique which can be scaled up for processing volume or number of simultaneously run reactions, without the limitation of overpressure or vacuum-driven filtration-based systems. We have developed synthesizers based on the power of centrifugation — peptide and small organic molecule synthesizers utilizing cotton as the synthetic substrate and inclusion volume chemistry, synthesizers for automation of “tea bag” synthesis, and synthesizers based on “tilted plate centrifugation”. The last technique was employed in an oligonucleotide production facility with the capacity of more than 10 million compounds per year.
Automated Purification of Plasmid DNA Using Paramagnetic Particles
Authors: Smith Don , White Douglas
Published: October 2018

We describe a reagent system and robotic method for purifying plasmid DNA for restriction digestion, PCR, and fluorescent sequencing applications. The method uses two types of Wizard® MagneSil™ paramagnetic particles. Following lysis and neutralization procedures, the first particle type binds and removes cell debris; the second type is then used to bind plasmid DNA from the cleared lysate. The particles are then washed to eliminate unwanted contaminants. Purified plasmid DNA is then eluted from the particles with nuclease free water. When using a cell mass of approximately 4 O.D.600, the yield is 10–12μg of DNA when using high copy number plasmid. When used in BigDye® terminator sequencing, these DNA templates typically yield read lengths greater than 700 bases and Phred 20 scores of 600 to 750 bases. This purification method has been adapted for use on several robotic platforms in a 96-well format.
ASTM E1989-98 — The New Instrument Control Standard
Authors: Staab Torsten A. , Elling John W.
Published: October 2018

The new ASTM E1989–98 Laboratory Equipment Control Interface Specification (LECIS) is a robust standard definition of equipment behavior while under remote control. The goal of the standardization effort is to facilitate “plug-and-play” integration of laboratory automation with standard hardware behavior and software interfaces. The LECIS standardizes laboratory equipment behavior and a message passing scheme between the controller and equipment that synchronizes this behavior. Commercial adoption of this new standard is well under way.
The Thought Experimental Method: Avicenna's Flying Man Argument
Authors: ADAMSON PETER , BENEVICH FEDOR
Published: October 2018

No argument from the Arabic philosophical tradition has received more scholarly attention than Avicenna's ‘flying man’ thought experiment, in which a human is created out of thin air and is able to grasp his existence without grasping that he has a body. This paper offers a new interpretation of the version of this thought experiment found at the end of the first chapter of Avicenna's treatment of soul in theHealing. We argue that it needs to be understood in light of an epistemological theory set out elsewhere by Avicenna, which allows that all the constitutive properties of an essence will be clear to someone who understands and considers that essence. On our reading, this theory is put to work in the ‘flying man’: because the flying man would grasp that his own essence has existence without grasping that he has a body, connection to body cannot be constitutive of the essence.
Justice in theLaws, a Restatement: Why Plato Endorses Public Reason
Authors: DIRECTOR SAMUEL
Published: October 2018

In theLaws, Plato argues that the legislator should attempt to persuade people to obey the laws voluntarily. This persuasion is accomplished through use of legislative preludes. In this essay, I argue that Plato's use of persuasive preludes shows that he endorses the core features of a public reason theory of political justification.
Prototype wireless sensors for monitoring subsurface processes in snow and firn
Authors: BAGSHAW ELIZABETH A. , KARLSSON NANNA B. , LOK LAI BUN , LISHMAN BEN , CLARE LINDSAY , NICHOLLS KEITH W. , BURROW STEVE , WADHAM JEMMA L. , EISEN OLAF , CORR HUGH , BRENNAN PAUL , DAHL-JENSEN DORTHE
Published: October 2018

The detection and monitoring of meltwater within firn presents a significant monitoring challenge. We explore the potential of small wireless sensors (ETracer+, ET+) to measure temperature, pressure, electrical conductivity and thus the presence or absence of meltwater within firn, through tests in the dry snow zone at the East Greenland Ice Core Project site. The tested sensor platforms are small, robust and low cost, and communicate data via a VHF radio link to surface receivers. The sensors were deployed in low-temperature firn at the centre and shear margins of an ice stream for 4 weeks, and a ‘bucket experiment’ was used to test the detection of water within otherwise dry firn. The tests showed the ET+ could log subsurface temperatures and transmit the recorded data through up to 150 m dry firn. Two VHF receivers were tested: an autonomous phase-sensitive radio-echo sounder (ApRES) and a WinRadio. The ApRES can combine high-resolution imaging of the firn layers (by radio-echo sounding) with in situ measurements from the sensors, to build up a high spatial and temporal resolution picture of the subsurface. These results indicate that wireless sensors have great potential for long-term monitoring of firn processes.
A Master Narrative for the History of Pakistan: Tracing the origins of an ideological agenda
Authors: QASMI ALI USMAN
Published: October 2018

The demand for the creation of Pakistan was based on a historical narrative built around the centrality of the Muslim community in India and its distinctiveness in terms of religious beliefs, cultural traits, and historical traditions. A particular understanding of the past was, in other words, central to the idea of Pakistan. As a result, soon after independence in 1947, a group of eminent historians got together to set up the All Pakistan History Conference. It received official support and patronage as the new state was eager to shape a historical narrative that could strengthen the argument for a distinct Muslim identity. This article looks at the development of this historiography in Pakistan. Unlike existing studies on this topic, which simply point out the ‘flaws’ in the history textbooks used in Pakistan, I will argue that the dominant historical narrative to be found in these textbooks—or even in many scholarly works produced in Pakistan—is a form of master narrative that has a longer history that dates back to the colonial period. Drawing upon such sources as historical texts produced in Pakistan, recently declassified documents of the Cabinet Division, and proceedings of the All Pakistan History Conference, I will delineate the features of this master narrative, the intellectual history of ideas that shaped it from the colonial to the post-colonial period, and the political exegesis whereby it gained structural dominance in Pakistan that was replicated for intellectual, ideological, and statist projects.
Expériences naturelles et causalité en histoire économique: Quels rapports à la théorie et à la temporalité ?
Authors: Bourgeois-Gironde Sacha , Monnet Éric
Published: October 2018

Un courant récent et influent, porté principalement par des économistes, propose de renouveler l'analyse historique à partir des notions d'expérience naturelle et de causalité. Il a la double ambition d'unifier diverses disciplines autour d'une acception commune de la causalité afin de réinterroger des grandes questions historiques (comme le rôle de la colonisation, des régimes politiques ou de la religion dans le développement économique) et de rendre l'analyse de l'histoire plus scientifique. La définition de la causalité qu'il promeut – de type interventionniste – vise à traiter les événements historiques comme un protocole d'expérience de laboratoire. Celle-ci s'articule avec une perspective néo-institutionnaliste visant à mesurer les effets dans la longue durée de certains changements institutionnels passés, considérés comme exogènes. Dans un premier temps, cet article présente les ambitions, les apports, les méthodes et les hypothèses (implicites et explicites) de ce courant de recherche, avant de montrer comment il se différencie de l'histoire économique quantitative plus traditionnelle, et de le resituer dans le contexte des récents tournants empirique et néo-institutionnaliste de la discipline économique. Dans un second temps, cet article fait état des critiques – souvent virulentes – formulées par des historiens ou des économistes à l'encontre de cette méthode et de ses objectifs. Enfin, nous insistons sur les difficultés de cette approche à prendre en compte l'historicité des phénomènes, à produire des énoncés généraux à partir de cas particuliers, et à proposer une définition complète et cohérente de la causalité en histoire.
Synchrotron X-ray diffraction study of double perovskites Sr2RNbO6 (R = Sm, Gd, Dy, Ho, Y, Tm, and Lu)
Authors: Wong-Ng W. , Kaduk J. A. , Lapidus S. H. , Ribaud L. , Diwanji S. P.
Published: October 2018

A series of double-perovskite oxides, Sr2RNbO6 (R = Sm, Gd, Dy, Ho, Y, Tm, and Lu) were prepared and their crystal structure and powder diffraction reference patterns were determined using the Rietveld analysis technique. The crystal structure of each of the Sr2RNbO6 phase is reported in this paper. The R = Gd, Ho, and Lu samples were studied using synchrotron radiation, while R = Sm, Dy, Y, and Tm samples were studied using laboratory X-ray diffraction. Members of Sr2RNbO6 are monoclinic with a space group of P21/n and are isostructural with each other. Following the trend of “lanthanide contraction”, from R = Sm to Lu, the lattice parameters “a” of these compounds decreases from 5.84672(10) to 5.78100(3) Å, b from 5.93192(13) to 5.80977(3) Å, c from 8.3142(2) to 8.18957(5) Å, and V decreases from 288.355(11) to 275.057(2) Å3. In this double-perovskite series, the R3+ and Nb5+ ions are structurally ordered. The average Nb–O bond length is nearly constant, while the average R–O bond length decreases with the decreasing ionic radius of R3+. Powder diffraction patterns for these compounds have been submitted to the Powder Diffraction File (PDF).
Ethics in humanitarian efforts: when should resources be allocated to paediatric heart surgery?
Authors: Fenton Kathleen N. , Cardarelli Marcelo , Molloy Frank , Novick William M.
Published: October 2018

Background

In countries with ample resources, no debate exists as to whether heart surgery should be provided. However, where funding is limited, what responsibility exists to care for children with congenital heart defects? If children have a “right” to surgical treatment, to whom is the “duty” to provide it assigned? These questions are subjected to ethical analysis.

Methods

Examination is initially based on the four principles of medical ethics: autonomy, beneficence, non-maleficence, and justice. Consideration of beneficence and justice is expanded using a consequentialist approach.

Results

Social structures, including governments, exist to foster the common good. Society, whether by means of government funding or otherwise, has the responsibility, according to the means available, to assure health care for all based on the principles of beneficence, non-maleficence, and justice. In wealthy countries, adequate resources exist to fund appropriate treatment; hence it should be provided to all based on distributive justice. In resource-limited countries, however, decisions regarding provision of care for expensive or complex health problems must be made with consideration for broader effects on the general public. Preliminary data from cost-effectiveness analysis indicate that many surgical interventions, including cardiac surgery, may be resource-efficient. Given that information, utilitarian ethical analysis supports dedication of resources to congenital heart surgery in many low-income countries. In the poorest countries, where access to drinking water and basic nutrition is problematic, it will often be more appropriate to focus on these issues first.

Conclusion

Ethical analysis supports dedication of resources to congenital heart surgery in all but the poorest countries.
Voluntary industry initiatives to promote healthy diets: a case study on a major European food retailer
Authors: von Philipsborn Peter , Stratil Jan Marcel , Heise Thomas Leonhard , Landgraf Rüdiger , Hauner Hans , Rehfuess Eva Annette
Published: October 2018

Objective

To analyse the scope and content of the nutrition pledge announced by Lidl.

Design

We applied the approach recommended by the private-sector module of the INFORMAS (International Network for Food and Obesity Research, Monitoring and Action Support) food environment monitoring framework and qualitative content analysis to Lidl’s nutrition pledge.

Setting

Global.

Subjects

The nutrition pledge of Lidl, Europe’s largest food retailer.

Results

Lidl pledges to reduce the average sales-weighted content of added sugar and added salt in its own-brand products by 20 % until 2025, using 2015 as a baseline, starting in Germany. Moreover, it vows to reduce the saturated and trans-fatty acid contents of its own-brand products, without specifying targets or timelines. To achieve these targets, it pledges to apply a number of approaches, including reformulation, promotion of healthier products, reduction of package and portion sizes, and provision of nutrition information and education. Strengths of Lidl’s pledge are its extensive scope, the quantification of some targets, and its partially evidence-based approach to the selection of targets and interventions. Key limitations include the vagueness of many targets, a lack of transparency and the absence of independent monitoring and evaluation.

Conclusions

Lidl’s pledge, while commendable for its scope, does not meet current best practice guidelines. Given their current limitations, industry initiatives of this kind are likely to fall short of what is needed to improve population-level nutrition.
Extracting Induced and Remanent Magnetizations From Magnetic Data Modeling
Authors: Liu Shuang , Fedi Maurizio , Hu Xiangyun , Baniamerian Jamaledin , Wei Bangshun , Zhang Dalian , Zhu Rixiang
Published: October 2018

To investigate the crustal magnetic structure, it is important to assess the susceptibility and remanence properties of rocks and ores. In this paper, we propose a method to extract the contributions of induced and remanent magnetization from modeling of magnetic anomalies. We first estimate the direction of the total magnetization vector by studying the reduced‐to‐pole anomaly and its correlation with different magnitude magnetic transforms. Then we invert the magnetic data to obtain the volumetric distribution of the magnetization intensity. As the third step, based on a priori information about the Koenigsberger ratio derived from petrophysical measurements, we extract the distributions in the source volume of the induced and remanent magnetization intensities, based on a generalized relationship involving the total and remanent magnetizations, and the true susceptibility. In this way, we are able to produce separate maps of the anomaly fields attributed to the physical magnetic source parameters: remanent and induced magnetization. After validating the method with synthetic data, we analyze the data relative to the Mesozoic and Cenozoic igneous rocks in Yeshan region, eastern China. The analysis of the separated magnetization components reveals that the intrusion of dioritic and basaltic rocks occurred at different geological periods, and the basaltic rocks were magnetized by a reversed geomagnetic field. The uncertainty analysis shows that a larger Koenigsberger ratio is beneficial to extract more reliable remanence and susceptibility information.
Regional‐Scale Precipitation Anomalies in Northern China During the Holocene and Possible Impact on Prehistoric Demographic Changes
Authors: Li Jianyong , Yan Hong , Dodson John , Xu Qinghai , Sun Aizhi , Cheng Bo , Li Chunhai , Ni Jian , Zhang Xiaojian , Lu Fengyan
Published: October 2018

Sensitive changes in precipitation influence the stability of semiarid ecosystem, rain‐fed agriculture, and densely populated society in northern monsoonal China (NC). However, shortage of regional‐scale quantitative syntheses imposes restrictions on investigating long‐term relationships among precipitation dynamics, possible climatic forces, and prehistoric demographic fluctuations. Herein, we contribute a regionally compiled anomaly record for Holocene annual mean precipitation (PANN) relative to its modern‐day values in NC. The Holocene PANN variations in NC may be essentially determined by changing thermal gradients of continental land‐ocean and west‐east equatorial Pacific, profoundly affecting strength and location of West Pacific Subtropical High that may principally modulate intensity of East Asian summer monsoon and resultant rainfall in NC. Importantly, variation partitioning analysis quantitatively demonstrates that the overall changes of precipitation (43.3%) may play a more important role than temperature (3.2%) and their shared effects (0.8%) in independently accounting for long‐term variation of regional‐scale Holocene population fluctuations in NC.
Climate‐Driven Change in the North Atlantic and Arctic Oceans Can Greatly Reduce the Circulation of the North Sea
Authors: Holt Jason , Polton Jeff , Huthnance John , Wakelin Sarah , O'Dea Enda , Harle James , Yool Andrew , Artioli Yuri , Blackford Jerry , Siddorn John , Inall Mark
Published: October 2018

We demonstrate for the first time a direct oceanic link between climate‐driven change in the North Atlantic and Arctic Oceans and the circulation of the northwest European shelf seas. Downscaled scenarios show a shutdown of the exchange between the Atlantic and the North Sea and a substantial decrease in the circulation of the North Sea in the second half of the 21st century. The northern North Sea inflow decreases from 1.2–1.3 Sv (1 Sv = 106 m3/s) to 0.0–0.6 Sv with Atlantic water largely bypassing the North Sea. This is traced to changes in oceanic haline stratification and gyre structure and to a newly identified circulation‐salinity feedback. The scenario presented here is of a novel potential future state for the North Sea, with wide‐ranging environmental management and societal impacts. Specifically, the sea would become more estuarine and susceptible to anthropogenic influence with an enhanced risk of coastal eutrophication.
A Simple Model for Deglacial Meltwater Pulses
Authors: Robel Alexander A. , Tsai Victor C.
Published: October 2018

Evidence from radiocarbon dating and complex ice sheet modeling suggests that the fastest rate of sea level rise in Earth's recent history coincided with collapse of the ice saddle between the Laurentide and Cordilleran ice sheets during the last deglaciation. In this study, we derive a simple, two‐equation model of two ice sheets intersecting in an ice saddle. We show that two conditions are necessary for producing the acceleration in ice sheet melt associated with meltwater pulses: the positive height‐mass balance feedback and an ice saddle geometry. The amplitude and timing of meltwater pulses is sensitively dependent on the rate of climate warming during deglaciation and the relative size of ice sheets undergoing deglaciation. We discuss how simulations of meltwater pulses can be improved and the prospect for meltwater pulses under continued climate warming.
Rheological Control of Lateral Growth of the Tibetan Plateau: Numerical Results
Authors: Sun Yujun , Liu Mian
Published: October 2018

The collision and continued convergence between the Indian and Eurasian plates in the past ~50 million years have raised the Tibetan Plateau, but whether or not, and how, the plateau has grown laterally remains controversial. Here we show that useful insights can be gained by studying lithospheric deformation across the front margins of the Tibetan Plateau. Crossing its northern and eastern sides where the plateau is bounded by the Tarim and Sichuan blocks, the topographic slope is steep and crustal deformation is localized near the margins of the plateau, whereas across northeastern Tibetan Plateau the topographic slope is gentle and crustal deformation is diffuse over a broad transition zone. Using a suite of two‐dimensional viscoplastic finite element models, we reproduced the major features of the two types of plateau margins with different rheological contrasts between the Tibetan Plateau and the bounding Asian blocks. Our results suggest that the bounding Asian blocks with a strong mantle lithosphere, such as the Tarim and the Sichuan Basins, have restricted the lateral growth of the Tibetan Plateau, although limited lateral expansion of the plateau can occur where the upper crust of these bounding blocks are relatively weak. Major lateral growth of the Tibetan Plateau mainly occurred northeastward, where numerous terranes with relatively weak mantle lithosphere are readily deformed and incorporated into the Tibetan Plateau. This growth front has reached the strong Alashan and Ordos blocks. Further lateral growth of the Tibetan Plateau depends on whether or not the Tibetan tectonics can weaken the mantle lithosphere of these Asian blocks.
Gravity Wave Behavior in Lower Stratosphere During Tropical Cyclones Over the Bay of Bengal
Authors: Rakshit Gargi , Jana Soumyajyoti , Maitra Animesh
Published: October 2018

Gravity waves associated with tropical cyclones over the Bay of Bengal have been studied using Constellation Observing System for Meteorology, Ionosphere, and Climate GPS radio occultation measurements. The sources of gravity waves are located well below the tropopause where the intensity of a tropical cyclone is high. The gravity wave potential energy between 19 and 26 km shows an enhancement in the lower stratosphere during the cyclone. Intense convection associated with tropical cyclone is characterized by low outgoing longwave radiation values. The present study shows an increase in potential energy in the lower stratosphere over a storm path before the actual occurrence of cyclones. The power spectral density of gravity waves shows that the vertical wavelengths in the range 2–2.4 km carry the maximum energy in the lower stratosphere over the cyclone path.
Radio Telescope Design Optimization Using Costing Constraints: Extrapolating LOFAR Costing to the Square Kilometre Array
Authors: Boonstra Albert‐Jan , Nijboer Ronald
Published: October 2018

In this paper we present a methodology for creating a system design for radio telescopes based on a fixed cost budget. This methodology builds on the idea to optimize a figure of merit such as sensitivity or survey speed given a model for the scaling of the cost of the components of a radio telescope. We applied the method of Lagrange multipliers to find the optimal design and we used cost scaling models based on our experience with the construction of the Low Frequency Array (LOFAR) telescope. We have extrapolated the LOFAR designs to the SKA1‐Low telescope and have assessed the current SKA1‐Low design in terms of figure of merit maximization. We have shown that, in the absence of other systems constraints such as point spread function requirements, in general, the chosen designs would be more sensitive if larger bandwidths and fewer and larger antenna stations would have been chosen. We have demonstrated that costs can be explicitly incorporated in the designs without adding too much complexity, so that it still is possible to find causal relations between cost, system design, and performance.
Efficient biosynthesis of heterodimeric C3-aryl pyrroloindoline alkaloids
Authors: Tian Wenya , Sun Chenghai , Zheng Mei , Harmer Jeffrey R. , Yu Mingjia , Zhang Yanan , Peng Haidong , Zhu Dongqing , Deng Zixin , Chen Shi-Lu , Mobli Mehdi , Jia Xinying , Qu Xudong
Published: October 2018

Many natural products contain the hexahydropyrrolo[2, 3-b]indole (HPI) framework. HPI containing chemicals exhibit various biological activities and distinguishable structural arrangement. This structural complexity renders chemical synthesis very challenging. Here, through investigating the biosynthesis of a naturally occurring C3-aryl HPI, naseseazine C (NAS-C), we identify a P450 enzyme (NascB) and reveal that NascB catalyzes a radical cascade reaction to form intramolecular and intermolecular carbon–carbon bonds with both regio- and stereo-specificity. Surprisingly, the limited freedom is allowed in specificity to generate four types of C3-aryl HPI scaffolds, and two of them were not previously observed. By incorporating NascB into an engineered strain of E. coli, we develop a whole-cell biocatalysis system for efficient production of NAS-C and 30 NAS analogs. Interestingly, we find that some of these analogs exhibit potent neuroprotective properties. Thus, our biocatalytic methodology offers an efficient and simple route to generate difficult HPI framework containing chemicals.
Author Correction: Genetic dissection of clonal lineage relationships with hydroxytamoxifen liposomes
Authors: Ransom Ryan C. , Foster Deshka S. , Salhotra Ankit , Jones Ruth Ellen , Marshall Clement D. , Leavitt Tripp , Murphy Matthew P. , Moore Alessandra L. , Blackshear Charles P. , Brett Elizabeth A. , Wan Derrick C. , Longaker Michael T.
Published: October 2018

In the original version of this Article, the authors inadvertently omitted Elizabeth A. Brett, who contributed to the generation of the histology figures, from the author list.This has now been corrected in both the PDF and HTML versions of the Article.
The Optimal Timing of Enterostomy Closure in Extremely Low Birth Weight Patients for Acute Abdomen
Authors: Yang Hee-Beom , Han Ji-Won , Youn Joong Kee , Oh Chaeyoun , Kim Hyun-Young , Jung Sung Eun
Published: October 2018

There are few reports on enterostomy closure (EC) timing for acute abdomen in extremely low birth weight (ELBW) patients. We retrospectively reviewed ELBW patients who underwent enterostomy formation (EF) and subsequent EC. We investigated baseline characteristics, surgical outcomes, and follow-up data of 55 patients and analyzed optimal timing by age at EC, enterostomy duration, and body weight (Bwt) at EC. The minimum p-value approach (MPA) using the Chi-squared test was used to determine each cut-off value. Mean gestational age was 25+3 weeks, while mean age and Bwt at EF were 10 days and 660 g. Enterostomy duration and Bwt at EC were 102 days and 2400 g. Fourteen surgical complications were related to EC. The MPA identified a cut-off of 2100 g (p = 0.039) at EC but no significant cut-off age or enterostomy duration. The 18 patients <2100 g had more enterostomy-related problems at EC than the >2100 g group (66.7% vs 10.8%, p < 0.001). No other characteristics were significantly different. Operation time, ventilator period, hospital stay, parenteral nutrition duration, and full feeding day were significantly longer in <2100 g patients. Follow-up Bwt did not differ (11.55 kg vs 13.95 kg, p = 0.324). Our findings suggest EC can be safely performed when Bwt is over 2100 g.
Targeting Mitochondrial Oxidative Phosphorylation Abrogated Irinotecan Resistance in NSCLC
Authors: Lee Soohyun , Lee Jae-Seon , Seo Jinho , Lee Seon-Hyeong , Kang Joon Hee , Song Jaewhan , Kim Soo-Youl
Published: October 2018

Anticancer drug resistance is a major challenge of cancer therapy. We found that irinotecan-resistant NSCLC cells showed increased mitochondrial oxidative phosphorylation compared to the drug sensitive NSCLC cells. Previously, we found that combined inhibition of aldehyde dehydrogenase using gossypol, and mitochondrial complex I using phenformin, effectively reduced oxidative phosphorylation in NSCLC. Here, we showed that targeting oxidative phosphorylation with gossypol and phenformin abrogated irinotecan resistance in NSCLC. Furthermore, irinotecan treatment by blocking oxidative phosphorylation induced synergistic anti-cancer effect in NSCLC. The pre-clinical xenograft model of human NSCLC also demonstrated a therapeutic response to the dual targeting treatment. Therefore, this combination of gossypol and phenformin increases irinotecan sensitivity as well as preventing irinotecan resistance.
Quantum interferometric generation of polarization entangled photons
Authors: Terashima Haruka , Kobayashi Satoshi , Tsubakiyama Takaho , Sanaka Kaoru
Published: October 2018

Quantum interference, like Hong-Ou-Mandel interference, has played an important role to test fundamental concepts in quantum physics. We experimentally show that the multiple quantum interference effects enable the generation of high-performance polarization entangled photons. These photons have a high-emission rate, are degenerate, have a broadband distribution, and are postselection free. A quantum interferometric scheme, based on a round-trip configuration of a double-pass polarization Sagnac interferometer, makes it possible to use the large generation efficiency of polarization entangled photons in the process of parametric down-conversion and to separate degenerate photon pairs into different optical modes with no requirement of postselection. We demonstrate experimentally that multiple quantum interference is not only an interesting fundamental quantum optical phenomenon but can be used for novel photonic quantum information technologies.
Aptamer-enabled uptake of small molecule ligands
Authors: Auwardt Supipi Liyamali , Seo Yeon-Jung , Ilgu Muslum , Ray Judhajeet , Feldges Robert R. , Shubham Shambhavi , Bendickson Lee , Levine Howard A. , Nilsen-Hamilton Marit
Published: October 2018

The relative ease of isolating aptamers with high specificity for target molecules suggests that molecular recognition may be common in the folds of natural RNAs. We show here that, when expressed in cells, aptamers can increase the intracellular concentrations of their small molecule ligands. We have named these aptamers as DRAGINs (Drug Binding Aptamers for Growing Intracellular Numbers). The DRAGIN property, assessed here by the ability to enhance the toxicity of their ligands, was found for some, but not all, aminoglycoside aptamers. One aptamer protected cells against killing by its ligand. Another aptamer promoted killing as a singlemer and protected against killing as a tandemer. Based on a mathematical model, cell protection vs. killing is proposed as governed by aptamer affinity and access to the inner surface of the cell membrane, with the latter being a critical determinant. With RNA molecules proposed as the earliest functional polymers to drive the evolution of life, we suggest that RNA aptamer-like structures present in primitive cells might have selectively concentrated precursors for polymer synthesis. Riboswitches may be the evolved forms of these ancient aptamer-like “nutrient procurers”. Aptamers with DRAGIN capability in the modern world could be applied for imaging cells, in synthetic cell constructs, or to draw drugs into cells to make “undruggable” targets accessible to small molecule inhibitors.
Determinants of mortality after hip fracture surgery in Sweden: a registry-based retrospective cohort study
Authors: Åhman Rasmus , Siverhall Pontus Forsberg , Snygg Johan , Fredrikson Mats , Enlund Gunnar , Björnström Karin , Chew Michelle S.
Published: October 2018

Surgery for hip fractures is associated with high mortality and morbidity. The causes of poor outcome are not fully understood and may be related to other factors than the surgery itself. The relative contributions of patient, surgical, anaesthetic and structural factors have seldom been studied together. This study, a retrospective registry-based cohort study of 14 932 patients undergoing hip fracture surgery in Sweden from 1st of January 2014 to 31st of December 2016, aimed to identify important predictors of mortality post-surgery. The independent predictive power of our included variables was examined using Cox proportional hazards modeling with all-cause mortality at longest follow-up as the outcome. Twelve independent variables were considered as interrelated ‘exposures’ and their individual adjusted effect within a single model were evaluated. Kaplan-Meier curves were also generated. Crude mortality rates were 8.2% at 30 days (95% CI 7.7–8.6%) and 23.6% at 365 days (95% CI 22.9–24.2%). Of the 12 factors entered into the Cox regression analysis, age (aHR1.06, p < 0.001), male gender (aHR 1.45, p < 0.001), ASA-PS-class (ASA 1&2 reference; ASA 3 aHR 2.12; ASA 4 aHR 4.79; ASA 5 aHR 12.57 respectively, p < 0.001) and PACU-LOS (aHR 1.01, p < 0.001) were significantly associated with mortality at longest follow-up (up to 3 years). University hospital status was protective (aHR 0.83, p < 0.001) in the same model. Age, gender and ASA-PS-class were strong predictors of mortality after surgery for hip fractures in Sweden. University hospital status and length of stay in the postoperative care unit were also identified as modifiable risk factors after multivariable adjustment and require confirmation in future studies.
Lattice Resonances and Local Field Enhancement in Array of Dielectric Dimers for Surface Enhanced Raman Spectroscopy
Authors: Černigoj Jernej , Silvestri Fabrizio , Stoevelaar L. Pjotr , Berzinš Jonas , Gerini Giampiero
Published: October 2018

In this paper, we propose the use of high refractive index dimers for the realization of a surface enhanced Raman spectroscopy substrate, with an average enhancement factor comparable to plasmonic structures. The use of low loss dielectric materials is favorable to metallic ones, because of their lower light absorption and consequently a much lower heating effect of the substrate. We combined two different mechanisms of field enhancement to overcome the main weakness of dielectric dimers: a low enhancement factor compared to the plasmonic ones. A first mechanisms is associated to surface lattice resonances. This generates a narrow-band high enhancement, which is exploited to enhance the excitation light. A second mechanism exploits the local field enhancement between the dimers’ resonators, for the band where the molecule Raman emission spectrum is located. The fact that both field enhancements can be tuned by acting on separate geometric parameters, makes possible to optimize the design for many different molecules. The optimized structure and its performance is presented together with a discussion of the different enhancement mechanisms.
Soft X-ray Reflection Spectroscopy for Nano-Scaled Layered Structure Materials
Authors: Majhi A. , Nayak Maheswar , Pradhan P. C. , Filatova E. O. , Sokolov A. , Schäfers F.
Published: October 2018

We introduce a novel approach that addresses the probing of interfacial structural phenomena in layered nano-structured films. The approach combines resonant soft x-ray reflection spectroscopy at grazing incidence near the “critical angle” with angular dependent reflection at energies around the respective absorption edges. Dynamic scattering is considered to determine the effective electron density and hence chemically resolved atomic profile across the structure based on simultaneous data analysis. We demonstrate application of the developed technique on the layered model structure C (20 Å)/B (40 Å)/Si (300 Å)/W (10 Å)/substrate. We precisely quantify atomic migration across the interfaces, a few percent of chemical changes of materials and the presence of impurities from top to the buried interfaces. The results obtained reveal the sensitivity of the approach towards resolving the compositional differences up to a few atomic percent. The developed approach enables the reconstruction of a highly spatio-chemically resolved interfacial map of complex nano-scaled interfaces with technical relevance to many emerging applied research fields.
Effort and performance in a cooperative activity are boosted by perception of a partner’s effort
Authors: Chennells Matthew , Michael John
Published: October 2018

In everyday life, people must often determine how much time and effort to allocate to cooperative activities. In the current study, we tested the hypothesis that the perception of others’ effort investment in a cooperative activity may elicit a sense of commitment, leading people to allocate more time and effort to the activity themselves. We developed an effortful task in which participants were required to move an increasingly difficult bar slider on a screen while simultaneously reacting to the appearance of virtual coins and earn points to share between themselves and their partner. This design allowed us to operationalize commitment in terms of participants’ investment of time and effort. Crucially, the cooperative activity could only be performed after a partner had completed a complementary activity which we manipulated to be either easy (Low Effort condition) or difficult (High Effort condition). Our results revealed participants invested more effort, persisted longer and performed better in the High Effort condition, i.e. when they perceived their partner to have invested more effort. These results support the hypothesis that the perception of a partner’s effort boosts one’s own sense of commitment to a cooperative activity, and consequently also one’s willingness to invest time and effort.
Target-distractor competition cannot be resolved across a saccade
Authors: Arkesteijn Kiki , Smeets Jeroen B. J. , Donk Mieke , Belopolsky Artem V.
Published: October 2018

When a distractor is presented in close spatial proximity to a target, a saccade tends to land in between the two objects rather than on the target. This robust phenomenon (also referred to as the global effect) is thought to reflect unresolved competition between target and distractor. It is unclear whether this landing bias persists across saccades since a saccade displaces the retinotopic representations of target and distractor. In the present study participants made successive saccades towards two saccadic targets which were presented simultaneously with an irrelevant distractor in close proximity to the second saccade target. The second saccade was either visually-guided or memory-guided. For the memory-guided trials, the second saccade showed a landing bias towards the location of the distractor, despite the disappearance of the distractor after the first saccade. In contrast, for the visually-guided trials, the bias was corrected and the landing bias was eliminated, even for saccades with the shortest intersaccadic intervals. This suggests that the biased saccade plan was remapped across the first saccade. Therefore, we conclude that the target-distractor competition was not resolved across a saccade, but can be resolved based on visual information that is available after a saccade.
A synthesis of modern organic carbon accumulation rates in coastal and aquatic inland ecosystems
Authors: Wilkinson Grace M. , Besterman Alice , Buelo Cal , Gephart Jessica , Pace Michael L.
Published: October 2018

Organic carbon accumulation in the sediments of inland aquatic and coastal ecosystems is an important process in the global carbon budget that is subject to intense human modification. To date, research has focused on quantifying accumulation rates in individual or groups of aquatic ecosystems to quantify the aquatic carbon sinks. However, there hasn’t been a synthesis of rates across aquatic ecosystem to address the variability in rates within and among ecosystems types. Doing so would identify gaps in our understanding of accumulation rates and potentially reveal carbon sinks vulnerable to change. We synthesized accumulation rates from the literature, compiling 464 rate measurements from 103 studies of carbon accumulated in the modern period (ca. 200 years). Accumulation rates from the literature spanned four orders of magnitude varying substantially within and among ecosystem categories, with mean estimates for ecosystem categories ranging from 15.6 to 73.2 g C m−2 y−1 within ecosystem categories. With the exception of lakes, mean accumulation rates were poorly constrained due to high variability and paucity of data. Despite the high uncertainty, the estimates of modern accumulation rate compiled here are an important step for constructing carbon budgets and predicting future change.
Multi-faceted computational assessment of risk and progression in oligodendroglioma implicates NOTCH and PI3K pathways
Authors: Halani Sameer H. , Yousefi Safoora , Velazquez Vega Jose , Rossi Michael R. , Zhao Zheng , Amrollahi Fatemeh , Holder Chad A. , Baxter-Stoltzfus Amelia , Eschbacher Jennifer , Griffith Brent , Olson Jeffrey J. , Jiang Tao , Yates Joseph R. , Eberhart Charles G. , Poisson Laila M. , Cooper Lee A. D. , Brat Daniel J.
Published: October 2018

Oligodendrogliomas are diffusely infiltrative gliomas defined by IDH-mutation and co-deletion of 1p/19q. They have highly variable clinical courses, with survivals ranging from 6 months to over 20 years, but little is known regarding the pathways involved with their progression or optimal markers for stratifying risk. We utilized machine-learning approaches with genomic data from The Cancer Genome Atlas to objectively identify molecular factors associated with clinical outcomes of oligodendroglioma and extended these findings to study signaling pathways implicated in oncogenesis and clinical endpoints associated with glioma progression. Our multi-faceted computational approach uncovered key genetic alterations associated with disease progression and shorter survival in oligodendroglioma and specifically identified Notch pathway inactivation and PI3K pathway activation as the most strongly associated with MRI and pathology findings of advanced disease and poor clinical outcome. Our findings that Notch pathway inactivation and PI3K pathway activation are associated with advanced disease and survival risk will pave the way for clinically relevant markers of disease progression and therapeutic targets to improve clinical outcomes. Furthermore, our approach demonstrates the strength of machine learning and computational methods for identifying genetic events critical to disease progression in the era of big data and precision medicine.