bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed passive / H∞ hybrid control for delayed Markovian jump system with actuator constraints and fault alarm
Authors: Li Jian‐Ning , Xu Yu‐Fei , Gu Kai‐Yang , Li Lin‐Sheng , Xu Xiao‐Bin
Published: October 2018

In this paper, mixed passive / H∞ hybrid controllers are designed for a delayed Markovian jump system with actuator constraints and alarm signal. The actuator constraints include the unknown actuator bias failure and the actuator partial failure, and the controllers are switched by using alarm signals. First, a sufficient condition for mixed passive / H∞ performance of the closed‐loop system is constructed, and robust controllers and fault‐tolerant controllers are designed, respectively. Then, mixed passive / H∞ observers are presented to ensure that the actuator bias failure is well estimated. Next, an alarm system is proposed by designing multiple thresholds to avoid false alarm, and this system is used to invoke suitable controllers and determine whether to remove the estimated value of actuator bias failure. Finally, two numerical examples are given to illustrate the effectiveness of the method.
Worm‐Like Biomimetic Nanoerythrocyte Carrying siRNA for Melanoma Gene Therapy
Authors: Wang Yanming , Ji Xin , Ruan Miaoliang , Liu Wen , Song Rongguang , Dai Jian , Xue Wei
Published: October 2018

A major challenge in siRNA vectors is developing approaches that ensure that when administered in vivo, the vectors can target their requisite site of action. This study reports a third type of nanoworm, biomimetic nanoerythrocytes for siRNA delivery, except for filomicelle and nanoworm iron‐oxide particle, which is the first approach that allows for targeted siRNA delivery by a process involving red blood cell (RBC) membrane cloaking of charge‐reversible polyplexes of siRNA and polycation. RBC membrane cloaking protects siRNA from RNase A degradation. Moreover, the RBC membrane‐cloaked charge‐reversible siRNA vector (RBC‐reversible polyplex (RP)) not only stays longer in the blood circulation than that of negatively charged bovine serum albumin (BSA) spheres and positively charged BSA, but is also able to escape from late endosomes/lysosomes, to achieve effective transfection for gene knockdown. The knockdown result in vivo is remarkably consistent with that of intracellular trafficking and transfection in vitro. Due to the outstanding biocompatibility and active targeting (cRGD), the 7 mg kg−1 dose siSurvivin in RGD‐RBC‐RP exhibits obviously superior anticancer effects at the animal level after two weeks. Therefore, the biomimetic worm‐like nanoerythrocyte charge‐reversible gene vector is a new and general method for highly efficient siRNA therapy in vivo.
Photoactivity and Stability Co‐Enhancement: When Localized Plasmons Meet Oxygen Vacancies in MgO
Authors: Liu Zhengqing , Lu Ziyang , Bosman Michel , Li Na , Frankcombe Terry J. , Jia Guohua , Tricoli Antonio , Liu Yun , Du Yaping , Yin Zongyou
Published: October 2018

Durability is still one of the key obstacles for the further development of photocatalytic energy‐conversion systems, especially low‐dimensional ones. Encouragingly, recent studies show that nanoinsulators such as SiO2 and MgO exhibit substantially enhanced photocatalytic durability than the typical semiconductor p25 TiO2. Extending this knowledge, MgO–Au plasmonic defect nanosystems are developed that combine the stable photoactivity from MgO surface defects with energy‐focusing plasmonics from Au nanoparticles (NPs), where Au NPs are anchored onto monodispersed MgO nanotemplates. Theoretical calculations reveal that the midgap defect (MGD) states in MgO are generated by oxygen vacancies, which provide the main avenues for upward electron transitions under photoexcitation. These electrons drive stable proton photoreduction to H2 gas via water splitting. A synergistic interaction between Au's localized plasmons and MgO's oxygen vacancies is observed here, which enhances MgO's photoactivity and stability simultaneously. Such co‐enhancement is attributed to the stable longitudinal‐plasmon‐free Au NPs, which provide robust hot electrons capable of overcoming the interband transition barrier (≈1.8 eV) to reach proton reduction potential for H2 generation. The demonstrated plasmonic defect nanosystems are expected to open a new avenue for developing highly endurable photoredox systems for the integration of multifunctionalities in energy conversion, environmental decontamination, and climate change mitigation.
Highly Efficient Copper Sulfide‐Based Near‐Infrared Photothermal Agents: Exploring the Limits of Macroscopic Heat Conversion
Authors: Marin Riccardo , Skripka Artiom , Besteiro Lucas V. , Benayas Antonio , Wang Zhiming , Govorov Alexander O. , Canton Patrizia , Vetrone Fiorenzo
Published: October 2018

Among the foreseeable therapeutic approaches at the cellular level, nanoplatform‐driven photothermal therapy is a thriving tool for the selective eradication of malignant tissues with minimal side effects to healthy ones. Hence, chemically versatile, near‐infrared absorbing plasmonic nanoparticles are distinctly appealing and most sought after as efficient photothermal agents. In this work, a straightforward method to synthesize monodisperse PEGylated copper sulfide nanoparticles of pure covellite (CuS) phase, featuring strong localized surface plasmonic resonance absorption in the near‐infrared and flexible surface chemistry, imparted by monomethyl ether polyethylene glycol molecules, is developed and optimized. These nanoparticles show a remarkable photothermal heat conversion efficiency (HCE) of 71.4%, which is among the highest for CuS systems and rivals that of plasmonic noble metal nanostructures. Moreover, through critical evaluation and mathematical modeling of the material's properties and measurement methodology, it is assessed that the calculated HCE values drastically depend on experimental conditions such as wavelength‐dependent solvent absorption properties, sol concentration, and optical path. These findings are of paramount relevance to the photothermal community, since they call for a standardization of the procedure for the evaluation of the HCE of proposed photothermal agents, in order to make the reported values universally and reliably comparable.
All‐in‐One Bifunctional Oxygen Electrode Films for Flexible Zn‐Air Batteries
Authors: Zeng Sha , Tong Xiao , Zhou Susheng , Lv Bo , Qiao Jian , Song Yanhui , Chen Minghai , Di Jiangtao , Li Qingwen
Published: October 2018

As a promising energy‐storage device, rechargeable Zn‐air batteries have attracted considerable interests. Herein, a bifunctional oxygen electrode film prepared by adhering NiCo2O4 nanosheets to a nitrogen and oxygen dual‐doped carbon nanotubes film in a large scale is reported. The resulting self‐supporting film electrode is multifunctional, which integrates a porous conducting structure for air diffusion and charge transfer, high‐performance catalysts for oxygen reduction and evolution, and novel structural flexibility. The composite film demonstrates excellent oxygen reduction/evolution reaction catalytic activities with low Tafel slopes (50 mV dec−1 for oxygen reduction reaction; 92 mV dec−1 for oxygen evolution reaction). Without any additional current collector, gas diffusion layer, or binder, the obtained bifunctional film performs as an “all‐in‐one” air electrode in a Zn‐air battery. A 50‐cm‐long cable‐shaped Zn‐air battery based on such a film air electrode exhibits high operating potentials (≈1.2 V at 0.25 mA cm−2), low charging–discharging overpotentials (≈0.7 V), and stable cycling performance. Moreover, the flexible cable Zn‐air batteries show excellent stability under different deformation conditions. The proposed concept of constructing scalable, all‐in‐one, freestanding, and flexible air electrodes would pave the way to develop next‐generation wearable and portable energy‐storage devices.
Perovskite Nanoparticles: Synthesis, Properties, and Novel Applications in Photovoltaics and LEDs
Authors: Kulkarni Sneha A. , Mhaisalkar Subodh G. , Mathews Nripan , Boix Pablo P.
Published: October 2018

Solar cells and light‐emitting diodes (LEDs) based on metal‐halide perovskites are transitioning from promising performers to direct competitors to well‐established technologies, with cost‐effectiveness as a strong advantage. Nanostructured perovskites have yielded record LEDs due to their higher versatility in the local management of charge carriers, which has enabled photoluminescence quantum yields (PLQYs) close to 100%. However, these perovskite nanostructures are yet to be fully exploited in other applications such as photovoltaics, where they can also present competitive advantages as they enable feasible routes to surpass the Shockley–Queisser limit by means of multiexciton generation or hot‐carrier extraction. Besides conventional applications, the extraordinary properties of these materials have the potential to unlock novel areas of research. Herein, the potential of perovskite nanostructures—with the focus on the widely developed nanoparticles—beyond classical thin‐film optoelectronics is analyzed, their limits of application are discussed, and their real possibilities are pondered.
Physicochemical, functional properties and ATR‐FTIR digestion analysis of thermally treated starches isolated from black and bayo beans
Authors: Chavez‐Murillo Carolina E. , Orona‐Padilla Jose L. , de la Rosa Millan Julian
Published: October 2018

Previous studies have related the slow digestion properties of isolated starches with their amylose to amylopectin ratio as well as their molecular structure, and in the case of flours, with their accompanying components such as proteins and fibers; which are known to restrict, to different extents the starch digestion by amylolytic enzymes. However, the botanical origin as well as the internal architecture of native starch granules plays a significant role in these characteristics. Moreover, these features can be improved by using hydrothermal treatments, such as heat moisture treatment (HMT) and annealing (ANN), that promote changes to granular architecture, increase internal crystallite order and decrease the amount of amorphous zones. In this study, HMT and ANN treated starches from two bean varieties and a normal maize starch are analyzed in terms of thermal stability, assessed by differential scanning calorimetry, viscosity by rapid visco analysis and in vitro amylolysis. The HMT and ANN treatments promote lower hydrolysis when compared to native granules, due to new and/or improved molecular interactions between starch molecules, assessed by attenuated total reflectance‐fourier transform infra red spectroscopy; such interactions increase the amount of crystalline residues after digestion, which is related with lower water absorption during cooking, and enhanced thermal stability, despite the lower enthalpies in thermal treated starches (≈3 J g−1 in Black bean with HMT). Furthermore, the hydrolysis residues after 120 min of amylolysis present a higher ratio of crystalline regions, that improve with thermal treatments, this demonstrates that these processes increase the order of existing crystallites due to new molecular interactions among starch molecules.
Activating Controlling Images in the Racialized Interaction Order: Black Middle‐Class Interactions and the Creativity of Racist Action
Authors: Meghji Ali
Published: October 2018

This paper investigates the link between the racial hierarchy and the racialized interaction order, questioning how controlling images of blackness are mediated in interactions. I explore this through interviews with thirty‐two black British middle‐class individuals, examining their interactions in the professional workplace. I argue that white people often draw on a practical knowledge of “white ignorance” to activate controlling images in their interactions with black professionals. This white ignorance allows for white people to find creative ways to irrationally deploy controlling images, and to adapt controlling images to specific interactional settings.
Endogenous cannabinoids mediate the effect of BDNF at CA1 inhibitory synapses in the hippocampus
Authors: Selvam Rajamani , Yeh Mason L. , Levine Eric S.
Published: October 2018

Brain‐derived neurotrophic factor (BDNF), traditionally known for promoting neuronal growth and development, is also a modulator of synaptic transmission. In addition to the well‐characterized effects at excitatory synapses, BDNF has been shown to acutely suppress inhibitory neurotransmission; however, the underlying mechanisms are unclear. We have previously shown that at inhibitory synapses in layer 2/3 of the somatosensory cortex, BDNF induces the mobilization of endogenous cannabinoids (eCBs) that act retrogradely to suppress GABA release. Here, we hypothesized that in the hippocampus, BDNF acts similarly via eCB signaling to suppress GABAergic transmission. We found that the acute application of BDNF reduced the spontaneous inhibitory postsynaptic currents (sIPSCs) via postsynaptic TrkB receptor activation. The suppressive effects of BDNF required eCB signaling, as this effect on sIPSCs was prevented by a CB1 receptor antagonist. Further, blocking the postsynaptic eCB release prevented the effect of BDNF, whereas eCB reuptake inhibition enhanced the effect of BDNF. These results suggest that BDNF triggers the postsynaptic release of eCBs. To identify the specific eCB release by BDNF, we tested the effects of disrupting the synthesis or degradation of 2‐arachidonoylcglycerol (2‐AG). Blocking 2‐AG synthesis prevented the effect of BDNF and blocking 2‐AG degradation enhanced the effect of BDNF. However, there was no change in the effect of BDNF when anandamide degradation was blocked. Collectively, these results suggest that in the hippocampus, BDNF‐TrkB signaling induces the postsynaptic release of the endogenous cannabinoid 2‐AG, which acts retrogradely on the presynaptic CB1 receptors to suppress GABA release.
Fuzzy‐sliding mode control of nonlinear smart base‐isolated building under earthquake excitation
Authors: Ghaffarzadeh Hosein , Ghaffari Amir Hossein , Yang T. Y.
Published: October 2018

In this paper, the effectiveness of the fuzzy sliding mode control strategy on three‐dimensional benchmark building with smart base isolation under seismic excitation has been examined. One of the appropriate control theories for such this nonlinear system is the sliding mode control theory; discontinuous sliding mode theory has weakness such as chattering phenomena. In this paper, we used a combination of fuzzy logic and sliding mode theory for the deletion of this defect. The proposed control theory has been scrutinized by applying on lately developed nonlinear three‐dimensional base‐isolated benchmark building. This building because of the three‐dimensional nature, coalescing of lateral and torsional responses, continuity of responses of the superstructure, and base is modeled with three degrees of freedom on every floor. In this building eight actuators assigned only at the base level and in the two directions (x, y). In other words, 16 actuators are located underneath the structure. Furthermore, the base isolation system has been modeled by considering lateral coupled equations for a better examination of the performance of the system. The results indicate that reduction of control performance is remarkable. Also, utilizing proposed control theory can decrease the responses of building in two main directions and, particularly, in the rotational degree of freedom.
Automatic visual inspection method for a coated surface having an orange peel effect
Authors: Yimit Adiljan , Itou Akiyoshi , Matsui Youichi , Akashi Takuya
Published: October 2018

In many production processes, defect detection has played an important role in preventing the outflow of defective products. As such, there are still many production lines that rely on an inspector's visual observation. In this study, using fluorescent tubes as an irradiation light source, we propose a simple and effective visual inspection method for detecting convex defect on painted surfaces having an orange peel effect. The proposed method detects and distinguishes painted surface defects in an area illuminated by fluorescent tubes, using the combination of local segmented results and gradient information computed with different differential operations. The inspection device for detecting the defect can be easily installed in the production line without changing the production line, and can be constructed at a low cost without using additional adaptations. The performance of the proposed method was evaluated with the data of real products captured with an inspection device installed on the production line. Experimental results show that this method can provide a better detection in the inspection region with a low false‐detection rate. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Maternal right ventricular function, uteroplacental circulation in first trimester and pregnancy outcome in women with congenital heart disease
Authors: Siegmund A. S. , Kampman M. A. M. , Oudijk M. A. , Mulder B. J. M. , Sieswerda G. T. J. , Koenen S. V. , Hummel Y. M. , de Laat M. W. M. , Sollie‐Szarynska K. M. , Groen H. , van Dijk A. P. J. , van Veldhuisen D. J. , Bilardo C. M. , Pieper P. G.
Published: October 2018

Objective

Pregnant women with congenital heart disease (CHD) have an increased risk of abnormal uteroplacental flow, measured from the second trimester onwards, which is associated with pregnancy complications affecting the mother and the fetus. Maternal right ventricular (RV) dysfunction has been suggested as a predisposing factor for impaired uteroplacental flow in these women. The aim of this study was to investigate the association of first‐trimester uteroplacental flow measurements with prepregnancy maternal cardiac function and pregnancy complications in women with CHD, with particular focus on the potential role of RV (dys)function.

Methods

This study included 138 pregnant women with CHD from the prospective ZAHARA III study (Zwangerschap bij Aangeboren HARtAfwijkingen; Pregnancy and CHD). Prepregnancy clinical and echocardiographic data were collected. Clinical evaluation, echocardiography (focused on RV function, as assessed by tricuspid annular plane systolic excursion (TAPSE)) and uterine artery (UtA) pulsatility index (PI) measurements were performed at 12, 20 and 32 weeks of gestation. Univariable and multivariable regression analyses were performed to assess the association between prepregnancy variables and UtA‐PI during pregnancy. The association between UtA‐PI at 12 weeks and cardiovascular, obstetric and neonatal complications was also assessed.

Results

On multivariable regression analysis, prepregnancy TAPSE was associated negatively with UtA‐PI at 12 weeks of gestation (β = −0.026; P = 0.036). Women with lower prepregnancy TAPSE (≤ 20 mm vs > 20 mm) had higher UtA‐PI at 12 weeks (1.5 ± 0.5 vs 1.2 ± 0.6; P = 0.047). Increased UtA‐PI at 12 weeks was associated with obstetric complications (P = 0.003), particularly hypertensive disorders (pregnancy‐induced hypertension and pre‐eclampsia, P = 0.019 and P = 0.026, respectively).

Conclusions

In women with CHD, RV dysfunction before pregnancy seems to impact placentation, resulting in increased resistance in UtA flow, which is detectable as early as in the first trimester. This, in turn, is associated with pregnancy complications. Early monitoring of uteroplacental flow might be of value in women with CHD with pre‐existing subclinical RV dysfunction to identify pregnancies that would benefit from close obstetric surveillance. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Variations on a Chip: Technologies of Difference in Human Genetics Research
Authors: Rajagopalan Ramya M. , Fujimura Joan H.
Published: October 2018

In this article we examine the history of the production of microarray technologies and their role in constructing and operationalizing views of human genetic difference in contemporary genomics. Rather than the “turn to difference” emerging as a post-Human Genome Project (HGP) phenomenon, interest in individual and group differences was a central, motivating concept in human genetics throughout the twentieth century. This interest was entwined with efforts to develop polymorphic “genetic markers” for studying human traits and diseases. We trace the technological, methodological and conceptual strategies in the late twentieth century that established single nucleotide polymorphisms (SNPs) as key focal points for locating difference in the genome. By embedding SNPs in microarrays, researchers created a technology that they used to catalog and assess human genetic variation. In the process of making genetic markers and array-based technologies to track variation, scientists also made commitments to ways of describing, cataloging and “knowing” human genetic differences that refracted difference through a continental geographic lens. We show how difference came to matter in both senses of the term: difference was made salient to, and inscribed on, genetic matter(s), as a result of the decisions, assessments and choices of collaborative and hybrid research collectives in medical genomics research.
The Emerging Roles of Steroid Hormone Receptors in Ductal Carcinoma in Situ (DCIS) of the Breast
Authors: Villanueva Hugo , Grimm Sandra , Dhamne Sagar , Rajapakshe Kimal , Visbal Adriana , Davis Christel M. , Ehli Erik A. , Hartig Sean M. , Coarfa Cristian , Edwards Dean P.
Published: October 2018

Ductal carcinoma in situ (DCIS) is a non-obligate precursor to most types of invasive breast cancer (IBC). Although it is estimated only one third of untreated patients with DCIS will progress to IBC, standard of care for treatment is surgery and radiation. This therapeutic approach combined with a lack of reliable biomarker panels to predict DCIS progression is a major clinical problem. DCIS shares the same molecular subtypes as IBC including estrogen receptor (ER) and progesterone receptor (PR) positive luminal subtypes, which encompass the majority (60–70%) of DCIS. Compared to the established roles of ER and PR in luminal IBC, much less is known about the roles and mechanism of action of estrogen (E2) and progesterone (P4) and their cognate receptors in the development and progression of DCIS. This is an underexplored area of research due in part to a paucity of suitable experimental models of ER+/PR + DCIS. This review summarizes information from clinical and observational studies on steroid hormones as breast cancer risk factors and ER and PR as biomarkers in DCIS. Lastly, we discuss emerging experimental models of ER+/PR+ DCIS.
Pioneering endoscopic retrograde cholangiopancreatography in a Sub Saharan African hospital: A case series
Authors: Michael Okello , Gerald Tumusiime , Viola Nabimanya , Steven Baguma , Ponsiano Ocama
Published: October 2018

ABSTRACT

Background and study aims:

Although endoscopic retrograde cholangiopancreatography (ERCP) was introduced in Europe, Asia and America over four decades ago, East Africa and Africa as a whole has been slow in taking up this very important minimally invasive procedure for the management of various hepatopancreaticobiliary conditions. This has led to reliance on open surgery for even simple benign biliary strictures, stones and malignant causes of biliary and pancreatic duct obstruction that can be treated endoscopically without a need for a morbid open surgical intervention. In Uganda, ERCP was introduced in January 2017 after obtaining training and equipment support from Senior Experten Service (SES), German. We therefore report the first six cases of ERCP performed at our endoscopy unit.

Patients and methods:

This is a case series report of six patients referred with yellowing of eyes and body itching as the main complaints. They predominantly had raised gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin and direct bilirubin. They also had different imaging investigations demonstrating hepatic ducts dilatation.

Results:

Four out of the six patients had complete post ERCP symptom resolution. One patient had partial symptom resolution and the other patient recovered after conversion to open surgery.

Conclusion:

Collaborative skills transfer made ERCP feasible in our institute and this marked the start of this specialised service in Uganda.

Highlights:
Platelets and Cardiovascular Disease
Authors: Willoughby Scott , Holmes Andrew , Loscalzo Joseph
Published: October 2018

Platelets play an important, but often under-recognized role in cardiovascular disease. For example, the normal response of the platelet can be altered, either by increased pro-aggregatory stimuli or by diminished anti-aggregatory substances to produce conditions of increased platelet activation/aggregation and occur in active cardiovascular disease states both on a chronic (e.g. stable angina pectoris) and acute basis (e.g. acute myocardial infarction). In addition, platelet hyperaggregability is also associated with the risk factors for coronary artery disease (e.g. smoking, hypertension, and hypercholesterolaemia). Finally, the utility of an increasing range of anti-platelet therapies in the management of the above disease states further emphasizes the pivotal role platelets play in the pathogenesis of cardiovascular disease. This paper provides a comprehensive overview of the normal physiologic role of platelets in maintain homeostasis, the pathophysiologic processes that contribute to platelet dysfunction in cardiovascular disease and the associated role and benefits of anti-platelet therapies.
Recruitment and Coaching of Healthy Elderly Subjects for Invasive Cardiovascular Research with Right-Sided Catheterisation
Authors: Bos Anja , Remmen Jaap J. , Aengevaeren Wim R.M. , Verheugt Freek W.A. , Hoefnagels Willibrord H.L. , Jansen René W.M.M.
Published: October 2018

Background and aims: Heart failure is primarily a disorder of the elderly. To investigate a non-invasive method to diagnose heart failure in the elderly, right-sided catheterisation was needed in healthy elderly subjects. We studied the feasibility of recruitment of healthy elderly subjects for this invasive investigation and aimed to identify the factors important for recruitment and for successful participation. Methods: Healthy subjects, aged ≥65 years, were invited by advertisement in a local newspaper to participate in an invasive study, preceded by extensive medical examination. An experienced research nurse provided coaching and care on an individual basis. Motivation to participate, satisfaction and the expected and perceived burden were assessed with a questionnaire before and after catheterisation. Results: From 180 subjects responding, 53 were invited for screening of whom 38 were included. Cardiovascular examination was the most important reason for participation. The questionnaire showed considerable satisfaction about the information and care given and about participating in the study in general. Conclusions: Recruitment of healthy elderly subjects for an invasive cardiovascular study is feasible. Individual coaching contributed to the satisfaction experienced. The appointment of an experienced research nurse appears important for successful recruitment and participation of healthy elderly subjects in an invasive cardiovascular study.
A Full Scanning System and a New Processing Method for Capillary Electrophoresis
Authors: Olazábal Virginia , Prasad Lakshman , Stark Peter , Olivares José A.
Published: October 2018

A system using a liquid-core waveguide for the full scanning of capillary electrophoresis processes is presented. The system utilizes the liquid-core waveguide as an efficient window for the excitation of separated samples and the collection of light through total internal reflectance, with zeptomolar detection limits. Scanning the excitation laser along the length of the electrophoresis capillary excites individually separated analyte bands, while the fluorescence is collected end-on by an optical fiber coupled to a photomultiplier. A new procedure for denoising and deconvolution was applied to the experimental electropherograms, removing the noise and resolving the highly overlapped peaks observed in early stages of the separation.
Evolution of High-Sensitivity Microarray Technology
Authors: Müller Uwe R.
Published: October 2018

Microarray technology is a multiplex analytical technique for the detection of many different analytes in a mixture of biomolecules. The detection limits for each of the analytes for which the array is designed depend on a multiplicity of reaction parameters, the array itself, and profoundly on the label and detection technology employed. Significant improvements in assay sensitivity have been achieved by optimizing all steps that affect the generation of signal and noise. Nanoparticle technology brings a new dimension to this technology by providing not only higher sensitivity but also improved specificity for hybridization-based microarray assay systems.
Evaluation of an Automated Cell Culture Incubator: The Autocell 200
Authors: Triaud F. , Darmon C. , Cariou Y. , Ferry N. , Le Neel T. , Clenet D. H. , Morin D. , Fraudeau C. , Blanchard D. , Truchaud A.
Published: October 2018

We evaluated the benefits of automation on the technical performance of a new automated cell culture incubator, the Autocell 200®, developed by Jouan SA. In addition, we assessed the potential interference of the embedded mechanical parts on cell culture growth. We measured a throughput of 150 plates loaded per hour, and 120 plates unloaded per hour, which is compatible with an external robotic handler. The mean time of robotic gate opening was 7 s. The gate pathway minimized climate disturbances inside the incubator. For CO2, we used a delay between opening events of 1 min. Biological assay results did not demonstrate a significant difference between the automated incubator and a traditional manual incubator, but we concluded that automation using the Autocell 200® could provide meaningful benefits for cell culture.
The Contribution of the Zimbabwe External Quality Assessment Schemein the Practice of Laboratory Medicine: 1989–1999
Authors: Matarira H T , Mujaji W B , Chin'ombe N. , Mlambo T. , Nyamayaro T.
Published: October 2018

The Department of Chemical Pathology of the University of Zimbabwe (Medical School) has set up an external quality assurance scheme, Zimbabwe External Quality Assessment Scheme (ZEQAS) to assess the quality of clinical chemistry laboratory performance in Zimbabwe. The programme has been in place since 1989. 43 clinical chemistry laboratories, both public and private, are currently participating in the quality assessment scheme. Analytical laboratory performance for participants is examined for twelve analytes. A standardized computer software package is used to process data and for producing performance charts. The information highlighted by a computer print-out for each participating laboratory includes the following: MRVIS (mean running variance index score) for all analytes, overall MRVIS for the laboratory, table of results for each analyte (with its mean value and cofficient of variation) and trimmed results for each analyte by individual method which include number of laboratories using a particular method, mean results for that particular method, SD (standard deviation) for that particular method and CV (coefficient of variation) for that particular method. Since the introduction of ZEQAS, there has been a drastic improvement in clinical chemistry laboratory performance in Zimbabwe. The overall mean running variance index score (OMRVIS) for all laboratories over a period from 1990 to 1999 has improved from 163 to 98.
Systems Development Strategy: A Component Based Approach, the Overview
Authors: Thakur Dinesh S. , Chen Vincent W. , Leister Kirk J.
Published: October 2018

A component-based framework is being developed which facilitates software re-use and provides faster integration of laboratory automation systems. Implementation of laboratory automation systems by the traditional approach usually takes significant development time since both module-level and application-level software are written custom to a particular application. In addition, modification and adaptation of an existing system developed by the traditional approach, to new and enhanced applications, usually requires significant reconfiguration to system software, since the modifications affect the way in which the module-level software interacts with each other. In order to reduce the development time and build flexible and easily re-configurable systems, a component-based framework is being developed that addresses the issue of software reuse and run-time configuration. This framework is based on a services based architecture and supports stateless components that can be configured at run-time. In addition, this framework supports polymorphic behavior for all its components thereby allowing for integrated substitution of hardware offering similar functions into an existing system to enhance its functionality. The basic overview and concepts of this framework in the context of laboratory automation systems is outlined in this paper.
Robotic and Automated Systems in the Pharmaceutical QC
Authors: Zick Franz , Fischer Manfred , Gulden Byk
Published: October 2018

Since the beginning of this decade the use of automated or robotic-systems for analytical purposes has decreased rapidely. Starting from the analysis of agriculturing products or medical samples, these instruments are now more and more common in the pharmaceutical industry. The systems are used for R&D purposes mainly in the area of combinatorial chemistry to analyze the huge amount of synthesis products in the biomedical labs and in chemical-physical laboratories of Quality Contol Units. Extensive stability studies, which have to be perfomed for new drug applications, and the release testing of medicinal products with a very high manufacturing batch-rate per year need highly effective analytical methods. Thus, Byk Gulden has introduced two automated systems based on Zymark products (TPWII and MultiDose), for the stability tests of an enteric-coated tablet. The number of batches, pack types and storage conditions (total number of samples: appr. 40 for the 3- and 6-months timepoints), for this stability study was required automation of the most time consuming test methods for purity, assay and dissolution of the tablets, because of the tight schedule for timepoints in the first year of storage (in general: two weeks). In order to have these automated systems in place for routine testing in a very short time, the method transfer from the manual procedure as well as the optimization and validation work (MTOV), were done completely by the supplier, Zymark. The other system, which is a customer designed robotic system built also by Zymark, is used for the release testing of an x-ray contrast medium with a very high batch-rate per year (approxmimately four batches per day that have to be analyzed). This enormous testing frequency is hardly to be realized by manual methods. Experiences with an already existent robotic systems has shown that the laboratory flow-through times are 30 to 50% decreased compared to manual testing.
Sample Acquisition and Control On-Chip Microfluidic Sample Preparation
Authors: Schulte Thomas , Bardell Ron , Weigl Bernhard H.
Published: October 2018

Microfluidic flow conditions allow the design of highly effective, yet simple devices for on-chip sample preparation and cleanup. Over the past few years, Micronics has developed a number of novel microfluidic structures that are compatible with complex samples such as whole blood or contaminated environmental fluids. The H-Filter is a technology based on the parallel laminar flow of two or more miscible streams in contact with each other. Such streams do not mix, but chemicals contained in these streams can diffuse from one stream into the other, with smaller molecules diffusing faster than larger ones. This principle can be used, for example, to remove salt from a solution containing DNA, or to extract smaller molecules from whole blood. The T-Sensor is based on the same laminar flow diffusion principle, but combines sample preparation with self-calibration and detection. These devices can be used not only in stand-alone research and point-of-use testing applications, but they can also be integrated, as sample preparation modules, into existing laboratory systems.
Generalized Dynamic Models of Gene Expression and Gene Classification
Authors: Dewey T. Gregory , Galas David J.
Published: October 2018

Powerful new experimental methods have been used to monitor changes in gene expression levels as a result of a variety of metabolic, xenobiotic or pathogenic challenges. Here we present a general approach to both statistical analysis and dynamic modeling of gene expression profiles that uses linear response theory. The formalism leads naturally to Markov models of the network reflected in the data, and provides a direct method of classifying genes according to their place in the resulting network. Non-linear and higher order Markov behavior of the network can also be included by a self-consistent method. In a sample data set from yeast, we calculate the Markov matrix and the gene classes based on the linear Markov network.
Increasing Productivity through a Combination of Automation and Robotics: A Case Study of Assay Services
Authors: Cheu Melissa , Myers Laurie
Published: October 2018

The Assay Services Department at Genentech, Inc., is a service laboratory that performs drug level measurement and antibody testing in support of pre-clinical animal studies and human clinical studies. As the number of Genentech products has increased, so have the number of studies, resulting in an annual increase in the number of samples generated and an increased demand for assay support. Assay Services has addressed this by increasing the efficiency and productivity of sample handling and assaying through the automation of various procedures. All sample dilutions are now done by automated dilutors, reducing the number of reassays and virtually eliminating the repetitive stress of manual sample dilutions. In addition, two complete ELISA robot stations have been in use over the last two years that have increased throughput by increasing the number of plates per run (a robot can assay ten to fifteen 96-well microtiter plates per run), and by allowing assays to run overnight without requiring the presence of lab personnel. The net gain from the automation efforts has been to double the number of samples run without increasing the number of lab personnel.
Development Process with the Aid of Automated Dissolution in Analytical Research and Development
Authors: Sadowitzs Jon P.
Published: October 2018

The development of drugs in the generic pharmaceutical industry is a highly competitive arena of companies vying for the few drug products that are coming off patent. Companies that have been successful in this arena are those that have met or surpassed the critical timeline associated with trial formulation development, analytical method development and submission batch manufacturing and testing.

Barr Laboratories has been successful in the Generic Pharmaceutical Industry for several reasons, one of which includes automation. The analytical research and development at Barr has employed the use of automated dissolution early in the lifecycle of a potential product. This approach has dramatically reduced the “Time To Market” on average for a number of products. The key to this approach is the network infrastructure of the formulation and analytical research and development departments. At Barr Laboratories Inc., our cooperative ability to work and communicate together has driven the departments to streamline and matrix their work efforts and optimize resources and time.

The discussion will reference how Barr Laboratories Inc., has been successful with automation and give a case study of products that have moved with rapid pace through the development cycle.
Performance Characteristics of an Automated Method for High-sensitivity CRP on the Roche Cobas Mira Analyzer
Authors: Huddleston David J. , Deitrick Cynthia L. , Budrean Stacy A. , Katholi Richard E.
Published: October 2018

C-Reactive protein assays with low end accuracy and reproducibility allow for use in risk stratification. We describe the K-ASSAY CRP-2 (Kamiya Biochemical Company, Seattle, WA) on the Roche Cobas Mira (Roche Diagnostics, Indianapolis, IN). Using an immunoturbidimetric principle, turbidity is compared to a stored calibration curve. Calibration stability is at least four weeks. Serum, EDTA-plasma and heparin-plasma provide comparable results. Intra- and inter-assay CV's are <2.55%. The regression equation against hs-CRP calibrators (Dade Behring, Deerfield, IL) is y = 1.11(x) − 0.18; r = 0.999. Quintiles from volunteer blood donors are provided.
Miniaturization of Sample Processing for Bioassays
Authors: Mariella Raymond
Published: October 2018

LLNL has recently licensed its hand-held advanced nucleic-acid analyzer, the HANAA, for commercial development. This (as is characteristic of other miniaturized, portable diagnostic instruments being developed around the world) typically still requires manual sample handling and preparation by skilled operators. Dielectrophoretic and acoustic manipulation of fluids and particles are techniques that have shown good promise to reduce the demands on manual sample preparation both for miniature and for table-top instrumentation.
Compound Characterization Using Gene Microarrays
Authors: Elbrecht Alex , Chen Yuli , Xu Jian , Gerhold David , Berger Joel , Adams Alan , Blevins Richard
Published: October 2018

Ligands for peroxisome proliferator activated receptors (PPARs) are used as hypolipidemic agents and for the treatment of type II diabetes, PPARa and PPARg, respectively. PPARs are members of the nuclear receptor family of ligand activated transcription factors which exert their effects primarily by regulating gene transcription. We have used gene microarrays to characterize PPAR ligands (profiling) and to investigate their mechanism of action. Compound profiles based on gene expression allow for novel ligand groupings when compared with groupings based on compound structure or on the results from single variable assays.
An Introduction to Using XML for the Management of Laboratory Data
Authors: Russo Mark F. , Rubin A. Erik
Published: October 2018

Extensible Markup Language (XML) and the XML Path Language (XPath) are introduced with software examples demonstrating how one can use them to write laboratory data management programs. Topics explored include XML document creation, manipulation, and searching. Programming examples make use of the Microsoft® XML Parser library and the Visual Basic programming language. The problem of managing microplate screening data is used as an illustration. Source code for all examples can be downloaded from http://www.labprogrammer.net .
Moving beyond Combinatorial Chemistry for Greater Efficiency in Lead Discovery
Authors: Edwards Paul J.
Published: October 2018

Pfizer Inc. is a research based global pharmaceutical company committed to the discovery and development of innovative medicines that improve the quality of life of individuals throughout the world. In order to gain a competitive advantage over competitor companies in the discovery of new medicines, we must speed up drug discovery and drive down costs. Using non-combinatorial chemistry techniques increases the efficiency with which we discover new ‘leads,’ leveraging our drug discovery efforts through retaining complete control over the properties of each product made. Compound purification, managed through in-house software, augments the quality of data obtained upon biological screening of compounds.
Automation of the Pre-Analytical Phase: A Performance Evaluation of Alternative Scenarios
Authors: De Capitani C. , Marocchi A. , Tolio T.
Published: October 2018

This paper is about the automation of the pre-analytical phase in a biochemical laboratory, which performs more than 3.7 million tests per year. The paper presents how an investment in the laboratory can be evaluated considering both economic criteria, future performance and service quality. The study comprises a workflow analysis of biological materials and information, the corresponding data collection and the use of simulation for performance evaluation. Alternative scenarios have been considered in terms of personnel, pre-analytical devices and management policies. The final scenario has been chosen according to economic criteria among a set of feasible scenarios, able to satisfy constraints.
Automation for High-Throughput Identification and Picking of GFP Expressing Colonies
Authors: Stephens Sarah , Figg Aaron , Mann Chris , Atkinson Robert , Woodrough Robert
Published: October 2018

Green fluorescent protein (GFP) has many applications as a marker in living cells, and has become widely used as a reporter gene in microbial, plant and animal cells. Screening microbial colonies for GFP expression enables various types of assays (e.g. for secretory mutations). However, this is laborious, non-quantitative and potentially hazardous to the operator (due to UV illumination) when performed manually. In order to address this the GloPix robot was developed. The imaging system discriminates between colonies based on the level of fluorescence activity and the picking function automatically transfers cells to microplate wells. Measuring fluorescent activity allows quantitation of fluorescent tag concentration/expression.
Flexible and Scalable Automation Solutions for Scoring Single Nucleotide Polymorphisms Using Rolling Circle Amplification
Authors: Ghouze Firman , Scozzafava Giuseppe , Oreo Ray , Hughes Barry , Roe Phyllida , Wheeler Claire , Howe Roland , Morris Stephen , Comley John
Published: October 2018

A single nucleotide polymorphism (SNP) scoring assay that uses ligation-dependent Rolling Circle Amplification (RCA)† was transferred to a series of automated protocols addressing a range of throughput levels. The systems utilised various automation modules consisting of custom-made and off-the-shelf devices. Several system parameters were evaluated to ensure assay integrity and homogeneity. These included reagent carry over, liquid evaporation rates, thermal regulation of reactions and fluorescence reading capabilities.

Data analysis software was developed in order to rapidly allocate SNP calls from data generated by the automated system. A modified fuzzy c-means clustering algorithm was employed to separate data points into groups associated with specific genotypes. Data were then presented graphically and within a summary table, which allowed easy and rapid organization and interpretation of data.
Customization of a Commercially Available Prep Scale SFC System to Provide Enhanced Capabilities
Authors: Olson Jeff , Pan Jeff , Hochlowski Jill , Searle Philip , Blanchard Dave
Published: October 2018

Preparative Scale Supercritical Fluid Chromatography is emerging as a powerful alternative to HPLC for the purification and separation of complex chemical reaction mixtures. Advantages include greatly reduced solvent usage (and thus lower cost and environmental impact), higher throughput, and in some cases higher resolution. While there are commercially available prep SFC instruments, none currently offer all the features desired by many medicinal chemists engaged in the drug discovery process. These include: the ability to collect an unlimited number of fractions per sample with high recovery and negligible carryover, fully automated capacity to collect several hundred fractions, and the ability to collect fractions into the same disposable test tubes and racks which are already employed in HPLC. This article describes the customization of a preparatory scale SFC system purchased from Berger Instruments, Inc., Newark, DE. (a subsidiary Mettler-Toledo International, Inc., of Greifensee, Switzerland) in order to provide these capabilities.