bluuebunny/crossref_metadata_2025 huggingface dataset:
Efeito da exposição à fumaça do cigarro sobre parâmetros comportamentais e peroxidação lipídica em camundongos
Authors: Martini Denise Zanatta , Mack Josiel Mileno , Linares Carlos Eduardo Blanco , Bolzan Rodrigo Cordeiro
Published: May 2018

O tabagismo é um dos principais fatores de risco para o desenvolvimento de várias doenças, dentre elas o câncer. Ao inalar a fumaça de cigarro, o organismo recebe, além da nicotina, capaz de promover alterações comportamentais, elevadas quantidades de substâncias reativas de oxigênio, capazes de promover o estresse oxidativo. Este trabalho examinou as alterações comportamentais em camundongos expostos à fumaça de cigarro em um padrão de exposição que simula a exposição humana em locais fechados, como bares e boates. Também foi avaliado o índice de peroxidação lipídica no fígado, cérebro e pulmão desses animais. Os resultados obtidos permitem verificar que ocorreu alteração comportamental no grupo de camundongos exposto à fumaça do cigarro, que se tornou mais ansioso e teve elevação da atividade exploratória. Essa modificação comportamental foi acompanhada de elevação do índice de peroxidação lipídica no cérebro desses animais. Conclui-se que a exposição de camundongos a fumaça do cigarro, mesmo por curto período de tempo, é capaz de produzir alterações comportamentais e induzir a degradação do tecido cerebral através da peroxidação lipídica, tornando-se um fator de risco para o desenvolvimento de câncer e de doenças degenerativas.
Aplicação dos biomodelos de prototipagem rápida na Odontologia, confeccionados pela técnica da impressão tridimensional
Authors: Safira Lucio Costa , Maciel Anderson Da Silva , Souto-Maior José Carlos Criales , Azevedo Roberto Almeida de , Cavalcante Weber Ceo , Francischone Carlos Eduardo , Sarmento Viviane Almeida
Published: May 2018

A Prototipagem Rápida (PR) é uma tecnologia de uso recente na Odontologia, que consiste na aquisição de biomodelos, compatíveis com a anatomia humana, a partir da associação da imaginologia médico-odontológica com sistemas de computadores (CAD - CAM). A confecção de biomodelos de prototipagem rápida assume grande importância na Cirurgia e Traumatologia Bucomaxilofacial e Implantodontia, por permitir um melhor planejamento cirúrgico. Esses modelos anatômicos facilitam a visualização da extensão da lesão e dos tecidos, o planejamento da cirurgia em todas as suas etapas e a utilização dos materiais cirúrgicos no modelo, reduzindo o tempo de intervenção cirúrgica. O objetivo deste trabalho é apresentar uma atualização sobre esse tema, ilustrada com biomodelos confeccionados pela técnica da Impressão Tridimensional (3DP- 3D Printing), utilizados em cirurgias realizadas no Hospital Santo Antônio (BA), e em hospitais privados de Salvador (BA).
A utilização de inibidores de PARP na profilaxia e no tratamento do câncer de mama deficiente no gene BRCA1
Authors: Lajus Tirzah Braz Petta
Published: May 2018

A enzima poli (ADP-ribose) polimerase-1 (PARP-1) representa um novo alvo importante na terapia-alvo do câncer. PARP-1 é essencial para o reparo de quebras no DNA via o reparo por excisão de base. Inibidores da PARP-1 têm mostrado um aumento nos efeitos citotóxicos das radiações ionizantes e das terapias quimioterápicas com os agentes de metilação e topoisomerase I. Neste momento, existem pelo menos cinco inibidores de PARP sendo testados em ensaios clínicos. Este artigo apresenta uma visão global dessa ferramenta na área de oncologia molecular e debate a real importância dessa descoberta no tratamento do câncer.
Novas perspectivas no tratamento da hiperplasia adrenal congênita
Authors: Faria Junior José Antônio Diniz , Sampaio Danilo Sousa , Oliveira Luciana Mattos Barros , Lago Renata , Silva Célia Nunes , Canguçu-Campinho Ana Karina , Schleu Minna , Toralles Maria Betânia Pereira
Published: May 2018

A HAC é um distúrbio congênito, caracterizado pela deficiência na biossíntese do cortisol, associado ou não à deficiência de aldosterona e, consequentemente, à superprodução de andrógeno. Essa condição afeta igualmente homens e mulheres. No sexo feminino, acarreta virilização da genitália externa em graus variados. No sexo masculino, nenhuma anormalidade se apresenta fenotipicamente ao nascimento. Tradicionalmente, o tratamento dessa síndrome consiste na reposição diária de glicocorticoides e mineralocorticoides. Novas terapias têm sido propostas com  intuito de se obterem resultados mais satisfatórios; dentre elas, existem: análogos do LHRH, GH, inibidores da aromatase, antiandrógenos e a adrenalectomia. Resultados preliminares apontam para uma melhora da altura final e do manejo clínico dos pacientes submetidos aos novos tratamentos. O objetivo deste estudo foi revisar a literatura acerca dessas novas modalidades terapêuticas, com o intuito de explorar o que há de mais novo na abordagem dessa síndrome.
Temporal and Spatial Matching in Human‐Earth System Model Coupling
Authors: Chou Jieming , Hu Chuanye , Dong Wenjie , Ban Jinghan
Published: May 2018

In the use of integrated assessment models to determine how the economy is affected by climate change, the bidirectional coupling of Earth system model with the integrated assessment model is needed. In the context of coupled problems in human‐Earth systems, two issues persist: spatial and temporal scale matching. For spatial scale matching, this paper proposes the area weight conversion method, a gridding method for calculations to accord with the grid of the Earth's system mode, where administrative data cells are transformed into grid data by “pregridding” and “postgridding.” For temporal scale matching, the temporal scale of the economic statistics was shortened to 1 year to render it consistent with the Earth system model. Using the area weight conversion method, grid processing was performed in terms of population and Gross Domestic Product for all provinces of China and every country of the world, respectively. The results showed that the characteristics of gridding population and Gross Domestic Product data were consistent with their actual distributions, that is, the credibility of gridding was high. The temporal matching treatment refined to the year and the spatial matching treatment following gridding met the overall requirements of coupling. Moreover, they provide a foundation for the coupling of the human‐Earth system model.
Geological Analysis of Martian Rover‐Derived Digital Outcrop Models Using the 3‐D Visualization Tool, Planetary Robotics 3‐D Viewer—PRo3D
Authors: Barnes Robert , Gupta Sanjeev , Traxler Christoph , Ortner Thomas , Bauer Arnold , Hesina Gerd , Paar Gerhard , Huber Ben , Juhart Kathrin , Fritz Laura , Nauschnegg Bernhard , Muller Jan‐Peter , Tao Yu
Published: May 2018

Panoramic camera systems on robots exploring the surface of Mars are used to collect images of terrain and rock outcrops which they encounter along their traverse. Image mosaics from these cameras are essential in mapping the surface geology and selecting locations for analysis by other instruments on the rover's payload. 2‐D images do not truly portray the depth of field of features within an image, nor their 3‐D geometry. This paper describes a new 3‐D visualization software tool for geological analysis of Martian rover‐derived Digital Outcrop Models created using photogrammetric processing of stereo‐images using the Planetary Robotics Vision Processing tool developed for 3‐D vision processing of ExoMars PanCam and Mars 2020 Mastcam‐Z data. Digital Outcrop Models are rendered in real time in the Planetary Robotics 3‐D Viewer PRo3D, allowing scientists to roam outcrops as in a terrestrial field campaign. Digitization of point, line, and polyline features is used for measuring the physical dimensions of geological features and communicating interpretations. Dip and strike of bedding and fractures is measured by digitizing a polyline along the contact or fracture trace, through which a best fit plane is plotted. The attitude of this plane is calculated in the software. Here we apply these tools to analysis of sedimentary rock outcrops and quantification of the geometry of fracture systems encountered by the science teams of NASA's Mars Exploration Rover Opportunity and Mars Science Laboratory rover Curiosity. We show the benefits PRo3D allows for visualization and collection of geological interpretations and analyses from rover‐derived stereo‐images.
A New Tool to Account for Crater Obliteration Effects in Crater Size‐Frequency Distribution Measurements
Authors: Riedel Christian , Michael Gregory , Kneissl Thomas , Orgel Csilla , Hiesinger Harald , van der Bogert Carolyn H.
Published: May 2018

The analysis of crater size‐frequency distributions (CSFDs) is a widely used technique to date and investigate planetary surface processes. There are two well‐established crater measurement techniques, traditional crater counting and buffered crater counting, and two new geometric corrections, nonsparseness correction and buffered nonsparseness correction. The new techniques consider the effects of crater obliteration and subsequent recratering while measuring CSFDs in areas of high crater density. Currently, the ArcGIS add‐in CraterTools can be used to apply the well‐established techniques. The tool relies on Esri's ArcGIS environment and is restricted to 32 bit and single‐core computing. These limitations make the implementation of the new geometric corrections in CraterTools inefficient, as the new techniques are computationally more intensive than the well‐established ones. To this end, we developed CSFD Tools, an application to conduct CSFD measurements from shapefiles. It supports 64 bit and multicore data processing and uses existing open geospatial libraries. Open libraries, however, conduct spatial measurements on a Cartesian plane and do not take a curved planetary surface into account. Therefore, we implemented methods for geodesic measurements and workarounds for the geodesic modification of polygon data to minimize map distortion effects during CSFD measurements. As a result, the new nonsparseness correction and buffered nonsparseness correction techniques can be applied through a software tool.
Altered dynamics of neurovascular coupling in CADASIL
Authors: Huneau Clément , Houot Marion , Joutel Anne , Béranger Benoit , Giroux Christian , Benali Habib , Chabriat Hugues
Published: May 2018

Background and Objective

Neurovascular coupling is the complex biological process that underlies use‐dependent increases in blood flow in response to neural activation. Neurovascular coupling was investigated at the early stage of CADASIL, a genetic paradigm of ischemic small vessel disease.

Methods

Functional hyperemia and evoked potentials during 20‐ and 40‐sec visual and motor stimulations were monitored simultaneously using arterial spin labeling‐functional magnetic resonance imaging (ASL‐fMRI) and electroencephalography.

Results

Cortical functional hyperemia differed significantly between 19 patients and 19 healthy individuals, whereas evoked potentials were unaltered. Functional hyperemia dynamics, assessed using the difference in the slope of the response curve between 15 and 30 sec, showed a time‐shifted decrease in the response to 40‐sec neural stimulations in CADASIL patients. These results were replicated in a second cohort of 10 patients and 10 controls and confirmed in the whole population.

Interpretation

Alterations of neurovascular coupling occur early in CADASIL and can be assessed by ASL‐fMRI using a simple marker of vascular dysfunction.
Patient Concerns and Perceptions Regarding Biologic Therapies in Ankylosing Spondylitis: Insights From a Large‐Scale Survey of Social Media Platforms
Authors: Dzubur Eldin , Khalil Carine , Almario Christopher V. , Noah Benjamin , Minhas Deeba , Ishimori Mariko , Arnold Corey , Park Yujin , Kay Jonathan , Weisman Michael H. , Spiegel Brennan M. R.
Published: May 2018

Objective

Few studies have examined ankylosing spondylitis (AS) patients’ concerns about and perceptions of biologic therapies, apart from traditional surveys. In this study, we used social media data to examine the knowledge, attitudes, and beliefs of AS patients regarding biologic therapies.

Methods

We collected posts published on 601 social media sites between January 1, 2016 and April 26, 2017. In each post, both an AS keyword and a biologic were mentioned. To explore themes within the collection of posts in an unsupervised manner, a latent Dirichlet allocation topic model was fit to the data set. Each discovered topic was represented as a discrete distribution over the words in the collection, similar to a word cloud. The topics were manually reviewed to identify themes, which were confirmed using thematic data analysis.

Results

We examined 27,416 social media posts and identified 112 themes. The majority of themes (n = 67 [60%]) focused on discussions related to AS treatment. Other themes, including the psychological impact of AS, reporting of medical literature, and AS disease consequences, accounted for the remaining 40% (n = 45). In discussions regarding AS treatment, most topics involved biologics, and most subthemes involved side effects (e.g., fatigue, allergic reactions), biologic treatment attributes (e.g., dosing, frequency), and concerns about use of biologics (e.g., increased cancer risk). Additional implicit patient needs (e.g., support) were identified using qualitative analyses.

Conclusion

Social media revealed a dynamic range of themes governing AS patients’ experience with and choice of biologic agents. The complexity of selecting biologics from among many such agents and navigating their risk/benefit profiles suggests the merit of creating online tools tailored to support patients’ decision‐making with regard to biologic therapies for AS.
HPV Oncogene Manipulation Using Nonvirally Delivered CRISPR/Cas9 or Natronobacterium gregoryi Argonaute
Authors: Lao Yeh‐Hsing , Li Mingqiang , Gao Madeleine A. , Shao Dan , Chi Chun‐Wei , Huang Dantong , Chakraborty Syandan , Ho Tzu‐Chieh , Jiang Weiqian , Wang Hong‐Xia , Wang Sihong , Leong Kam W.
Published: May 2018

CRISPR/Cas9 technology enables targeted gene editing; yet, the efficiency and specificity remain unsatisfactory, particularly for the nonvirally delivered, plasmid‐based CRISPR/Cas9 system. To tackle this, a self‐assembled micelle is developed and evaluated for human papillomavirus (HPV) E7 oncogene disruption. The optimized micelle enables effective delivery of Cas9 plasmid with a transient transgene expression profile, benefiting the specificity of Cas9 recognition. Furthermore, the feasibility of using the micelle is explored for another nucleic acid‐guided nuclease system, Natronobacterium gregoryi Argonaute (NgAgo). Both systems are tested in vitro and in vivo to evaluate their therapeutic potential. Cas9‐mediated E7 knockout leads to significant inhibition of HPV‐induced cancerous activity both in vitro and in vivo, while NgAgo does not show significant E7 inhibition on the xenograft mouse model. Collectively, this micelle represents an efficient delivery system for nonviral gene editing, adding to the armamentarium of gene editing tools to advance safe and effective precision medicine‐based therapeutics.
A Review of Electrocatalytic Reduction of Dinitrogen to Ammonia under Ambient Conditions
Authors: Cui Xiaoyang , Tang Cheng , Zhang Qiang
Published: May 2018

The production of ammonia (NH3) from molecular dinitrogen (N2) under mild conditions is one of the most attractive topics in the field of chemistry. Electrochemical reduction of N2 is promising for achieving clean and sustainable NH3 production with lower energy consumption using renewable energy sources. To date, emerging electrocatalysts for the electrochemical reduction of N2 to NH3 at room temperature and atmospheric pressure remain largely underexplored. The major challenge is to achieve both high catalytic activity and high selectivity. Here, the recent progress on the electrochemical nitrogen reduction reaction (NRR) at ambient temperature and pressure from both theoretical and experimental aspects is summarized, aiming at extracting instructive perceptions for future NRR research activities. The prevailing theories and mechanisms for NRR as well as computational screening of promising materials are presented. State‐of‐the‐art heterogeneous electrocatalysts as well as rational design of the whole electrochemical systems for NRR are involved. Importantly, promising strategies to enhance the activity, selectivity, efficiency, and stability of electrocatalysts toward NRR are proposed. Moreover, ammonia determination methods are compared and problems relating to possible ammonia contamination of the system are mentioned so as to shed fresh light on possible standard protocols for NRR measurements.
Self‐Limited on‐Site Conversion of MoO3 Nanodots into Vertically Aligned Ultrasmall Monolayer MoS2 for Efficient Hydrogen Evolution
Authors: Huang Lin‐Bo , Zhao Lu , Zhang Yun , Chen Yu‐Yun , Zhang Qing‐Hua , Luo Hao , Zhang Xing , Tang Tang , Gu Lin , Hu Jin‐Song
Published: May 2018

MoS2 has emerged as a promising alternative electrocatalyst for the hydrogen evolution reaction (HER) due to high intrinsic per‐site activity on its edge sites and S‐vacancies. However, a significant challenge is the limited density of such sites. Reducing the size and layer number of MoS2 and vertically aligning them would be an effective way to enrich and expose such sites for HER. Herein, a facile self‐limited on‐site conversion strategy for synthesizing monolayer MoS2 in a couple of nanometers which are highly dispersed and vertically aligned on 3D porous carbon sheets is reported. It is discovered that the preformation of well‐dispersed MoO3 nanodots in 1–2 nm as limited source is the key for the fabrication of such an ultrasmall MoS2 monolayer. As indicated by X‐ray photoelectron spectroscopy and electron spin resonance data, these ultrasmall MoS2 monolayers are rich in accessible S‐edge sites and vacancies and the smaller MoS2 monolayers the more such sites they have, leading to enhanced electrocatalytic activity with a low overpotential of 126 mV at 10 mA cm−2 and 140 mV at 100 mA mg−1 for HER. This state‐of‐the‐art performance for MoS2 electrocatalysts enables the present strategy as a new avenue for exploring well‐dispersed ultrasmall nanomaterials as efficient catalysts.
If these crawls could talk: Studying and documenting web archives provenance
Authors: Maemura Emily , Worby Nicholas , Milligan Ian , Becker Christoph
Published: May 2018

The increasing use and prominence of web archives raises the urgency of establishing mechanisms for transparency in the making of web archives to facilitate the process of evaluating a web archive's provenance, scoping, and absences. Some choices and process events are captured automatically, but their interactions are not currently well understood or documented. This study examined the decision space of web archives and its role in shaping what is and what is not captured in the web archiving process. By comparing how three different web archives collections were created and documented, we investigate how curatorial decisions interact with technical and external factors and we compare commonalities and differences. The findings reveal the need to understand both the social and technical context that shapes those decisions and the ways in which these individual decisions interact. Based on the study, we propose a framework for documenting key dimensions of a collection that addresses the situated nature of the organizational context, technical specificities, and unique characteristics of web materials that are the focus of a collection. The framework enables future researchers to undertake empirical work studying the process of creating web archives collections in different contexts.
A Stealth Integrity Targeted Cyber‐Attack in Distributed Electric Power Networks with Local Model Information
Authors: Ahmadloo Fatemeh , Salmasi Farzad Rajaei
Published: May 2018

Electric power networks are critical infrastructures, and their correct operation is of vital importance. Nowadays, these systems are prone to cyber‐attacks because of new vulnerabilities in the system and access to shared networks. In this paper, a novel Stealth Integrity Targeted Attack (SITA) is proposed in the context of distributed power systems. A distributed power system comprises several sub‐networks, or zones with dedicated control and monitoring centers. The overall system is represented by linear time invariant state space models with coupled dynamical and algebraic equations. In the proposed strategy, the attacker has access to only one of the sub networks; therefore, the attacker only requires local information about one of the power system zones. Primarily, the proposed attack policy is defined based on zero‐dynamics of the sub network. The intruder injects predesigned signals to both the local generation unit controller as well as local unsecured and controllable loads in the attacked zone. Moreover, the local measurement system, or the sensors of the targeted zone are tampered. Furthermore, it will be proved that although the neighbor zones have physical connections with the attacked zone, the injected adversary signals are designed as they do not impact other zones directly in order to conceal the local attack from neighbor control centers as much as possible. We provide some advice to system administrators to make the intrusion unfeasible or to reveal the attack. The simulations on IEEE‐118 bus test system illustrate the validity of the assertions.
Improved Performance in Mammalian Cell Perfusion Cultures by Growth Inhibition
Authors: Wolf Moritz K. F , Closet Aurélie , Bzowska Monika , Bielser Jean‐Marc , Souquet Jonathan , Broly Hervé , Morbidelli Massimo
Published: May 2018

Mammalian cell perfusion cultures represent a promising alternative to the current fed‐batch technology for the production of various biopharmaceuticals. Long‐term operation at a fixed viable cell density (VCD) requires a viable culture and a constant removal of excessive cells. Product loss in the cell removing bleed stream deteriorates the process yield. In this study, the authors investigate the use of chemical and environmental growth inhibition on culture performance by either adding valeric acid (VA) to the production media or by reducing the culture temperature (33.0 °C) with respect to control conditions (36.5 °C, no VA). Low temperature significantly reduces cellular growth, thus, resulting in lower bleed rates accompanied by a reduced product loss of 11% compared to 26% under control conditions. Additionally, the cell specific productivity of the target protein improves and maintained stable leading to media savings per mass of product. VA shows initially an inhibitory effect on cellular growth. However, cells seemed to adapt to the presence of the inhibitor resulting in a recovery of the cellular growth. Cell cycle and Western blot analyses support the observed results. This work underlines the role of temperature as a key operating variable for the optimization of perfusion cultures.
Early identification of unusually clustered mutations and root causes in therapeutic antibody development
Authors: Qian Yueming , Chen Zhiqiang , Huang Xin , Wang Xuning , Xu Xuankuo , Kirov Stefan , Ludwig Richard , Qian Nan‐Xin , Ravi Kandasamy , Tao Li , Borys Michael C. , Li Zheng Jian
Published: May 2018

This study reports findings of an unusual cluster of mutations spanning 22 bp (base pairs) in a monoclonal antibody expression vector. It was identified by two orthogonal methods: mass spectrometry on expressed protein and next‐generation sequencing (NGS) on the plasmid DNA. While the initial NGS analysis confirmed the designed sequence modification, intact mass analysis detected an additional mass of the antibody molecule expressed in CHO cells. The extra mass was eventually found to be associated with unmatched nucleotides in a distal region by checking full‐length sequence alignment plots. Interestingly, the complementary sequence of the mutated sequence was a reverse sequence of the original sequence and flanked by two 10‐bp reverse‐complementary sequences, leading to an undesirable DNA recombination. The finding highlights the necessity of rigorous examination of expression vector design and early monitoring of molecule integrity at both DNA and protein levels to prevent clones from having sequence variants during cell line development.
Morphological analysis of pore size and connectivity in a thick mixed‐culture biofilm
Authors: Rosenthal Alex F. , Griffin James S. , Wagner Michael , Packman Aaron I. , Balogun Oluwaseyi , Wells George F.
Published: May 2018

Morphological parameters are commonly used to predict transport and metabolic kinetics in biofilms. Yet, quantification of biofilm morphology remains challenging because of imaging technology limitations and lack of robust analytical approaches. We present a novel set of imaging and image analysis techniques to estimate internal porosity, pore size distributions, and pore network connectivity to a depth of 1 mm at a resolution of 10 µm in a biofilm exhibiting both heterotrophic and nitrifying activities. Optical coherence tomography (OCT) scans revealed an extensive pore network with diameters as large as 110 µm directly connected to the biofilm surface and surrounding fluid. Thin‐section fluorescence in situ hybridization microscopy revealed that ammonia‐oxidizing bacteria (AOB) distributed through the entire thickness of the biofilm. AOB were particularly concentrated in the biofilm around internal pores. Areal porosity values estimated from OCT scans were consistently lower than those estimated from multiphoton laser scanning microscopy, though the two imaging modalities showed a statistically significant correlation (r = 0.49, p < 0.0001). Estimates of areal porosity were moderately sensitive to gray‐level threshold selection, though several automated thresholding algorithms yielded similar values to those obtained by manually thresholding performed by a panel of environmental engineering researchers (±25% relative error). These findings advance our ability to quantitatively describe the geometry of biofilm internal pore networks at length scales relevant to engineered biofilm reactors and suggest that internal pore structures provide crucial habitat for nitrifier growth.
Low‐adhesive ethylene vinyl alcohol–based packaging to xenogeneic islet encapsulation for type 1 diabetes treatment
Authors: Yang Kai‐Chiang , Yanai Goichi , Yang Sin‐Yu , Canning Priyadarshini , Satou Yoshio , Kawagoe Masako , Sumi Shoichiro
Published: May 2018

Transplantation of encapsulated porcine islets is proposed to treat type 1 diabetes. However, the envelopment of fibrous tissue and the infiltration of immune cells impair islet function and eventually cause implant failure. It is known that hemodialysis using an ethylene vinyl alcohol (EVOH) membrane results in minor tissue responses. Therefore, we hypothesized that using a low‐adhesive EVOH membrane for encapsulation may prevent host cell accumulation and fibrous capsule formation. In this study, rat islets suspended in chitosan gel were encapsulated in bags made from highly porous EVOH membranes, and their in vitro insulin secretion function as well as in vivo performance was evaluated. The results showed that the EVOH bag did not affect islet survival or glucose‐stimulated insulin secretion. Whereas naked islets were dysfunctional after 7 days of culture in vitro, islets within the EVOH bag produced insulin continuously for 30 days. Streptozotocin‐induced diabetic mice were given islets–chitosan gel–EVOH implants intraperitoneally (650–800 islets equivalent) and exhibited lower blood glucose levels and regained body weight during a 4‐week observation period. The transplanted mice had higher levels of serum insulin and C‐peptide, with an improved blood glucose disappearance rate. Retrieved implants had minor tissue adhesion, and histology showed a limited number of mononuclear cells and fibroblasts surrounding the implants. No invasion of host cells into the EVOH bags was noticed, and the encapsulated islets were intact and positive for insulin–glucagon immunostaining. In conclusion, an EVOH bag can protect encapsulated islets, limit fibrous capsule formation, and extend graft function.
Boosting mediated electron transfer in bioelectrochemical systems with tailored defined microbial cocultures
Authors: Schmitz Simone , Rosenbaum Miriam A.
Published: May 2018

Bioelectrochemical systems (BES) hold great promise for sustainable energy generation via a microbial catalyst from organic matter, for example, from wastewater. To improve current generation in BES, understanding the underlying microbiology of the electrode community is essential. Electron mediator producing microorganism like Pseudomonas aeruginosa play an essential role in efficient electricity generation in BES. These microbes enable even nonelectroactive microorganism like Enterobacter aerogenes to contribute to current production. Together they form a synergistic coculture, where both contribute to community welfare. To use microbial co‐operation in BES, the physical and chemical environments provided in the natural habitats of the coculture play a crucial role. Here, we show that synergistic effects in defined cocultures of P. aeruginosa and E. aerogenes can be strongly enhanced toward high current production by adapting process parameters, like pH, temperature, oxygen demand, and substrate requirements. Especially, oxygen was identified as a major factor influencing coculture behavior and optimization of its supply could enhance electric current production over 400%. Furthermore, operating the coculture in fed‐batch mode enabled us to obtain very high current densities and to harvest electrical energy for 1 month. In this optimized condition, the coulombic efficiency of the process was boosted to 20%, which is outstanding for mediator‐based electron transfer. This study lays the foundation for a rationally designed utilization of cocultures in BES for bioenergy generation from specific wastewaters or for bioprocess sensing and for benefiting from their synergistic effects under controlled bioprocess condition.
Bioengineering triacetic acid lactone production in Yarrowia lipolytica for pogostone synthesis
Authors: Yu James , Landberg Jenny , Shavarebi Farbod , Bilanchone Virginia , Okerlund Adam , Wanninayake Umayangani , Zhao Le , Kraus George , Sandmeyer Suzanne
Published: May 2018

Yarrowia lipolytica is an oleaginous yeast that is recognized for its ability to accumulate high levels of lipids, which can serve as precursors to biobased fuels and chemicals. Polyketides, such as triacetic acid lactone (TAL), can also serve as a precursor for diverse commodity chemicals. This study used Y. lipolytica as a host organism for the production of TAL via expression of the 2‐pyrone synthase gene from Gerbera hybrida. Induction of lipid biosynthesis by nitrogen‐limited growth conditions increased TAL titers. We also manipulated basal levels of TAL production using a DNA cut‐and‐paste transposon to mobilize and integrate multiple copies of the 2‐pyrone synthase gene. Strain modifications and batch fermentation in nitrogen‐limited medium yielded TAL titers of 2.6 g/L. Furthermore, we show that minimal medium allows TAL to be readily concentrated at >94% purity and converted at 96% yield to pogostone, a valuable antibiotic. Modifications of this reaction scheme yielded diverse related compounds. Thus, oleaginous organisms have the potential to be flexible microbial biofactories capable of economical synthesis of platform chemicals and the generation of industrially relevant molecules.
Microdevice‐based solid‐phase polymerase chain reaction for rapid detection of pathogenic microorganisms
Authors: Pham Quang Nghia , Trinh Kieu The Loan , Jung Seung Won , Lee Nae Yoon
Published: May 2018

We demonstrate the integration of DNA amplification and detection functionalities developed on a lab‐on‐a‐chip microdevice utilizing solid‐phase polymerase chain reaction (SP‐PCR) for point‐of‐need (PON) DNA analyses. First, the polycarbonate microdevice was fabricated by thermal bonding  to contain microchambers as reservoirs for performing SP‐PCR. Next, the microchambers were subsequently modified with polyethyleneimine and glutaraldehyde for immobilizing amine‐modified forward primers. During SP‐PCR, the immobilized forward primers and freely diffusing fluorescence‐labeled reverse primers cooperated to generate target amplicons, which remained covalently attached to the microchambers for the fluorescence detection. The SP‐PCR microdevice was used for the direct identifications of two widely detected foodborne pathogens, namely Salmonella spp. and Staphylococcus aureus, and an alga causing harmful algal blooms annually in South Korea, Cochlodinium polykrikoides. The SP‐PCR microdevice would be versatilely applied in PON testing as a universal platform for the fast identification of foodborne pathogens and environmentally threatening biogenic targets.
Acute blood pressure levels and long‐term outcome in ischemic stroke
Authors: Bager Johan‐Emil , Hjalmarsson Clara , Manhem Karin , Andersson Bjorn
Published: May 2018

Objectives

Elevated blood pressure (BP) is common in acute ischemic stroke, but its effect on outcome is not fully understood. We aimed to investigate the association of baseline BP and BP change within the first day after stroke with stroke severity, functional outcome, and mortality.

Methods

Patients admitted to hospital with acute ischemic stroke (IS) from 15 February 2005 through 31 May 2009 were consecutively included. Acute stroke severity and functional outcome at three and twelve months were investigated using multivariate regression analysis; the association between BP and all‐cause mortality at one, three, and twelve was investigated by Cox proportional hazard regression and Kaplan–Meier survival curves.

Results

A total of 799 patients (mean age 78.4 ± 8.0, 48% men) were included. Higher decreases in systolic and mean arterial blood pressure (ΔSBP and ΔMAP) were associated with decreased 1‐month mortality (ΔSBP: hazard ratio, HR: 0.981; 95% CI: 0.968 – 0.994; p = .005), 3‐month mortality (ΔSBP: HR 0.989; 95% CI 0.981 – 0.998; p‐value .014), and twelve‐month mortality (ΔSBP: HR 0.989; 95% CI 0.982 – 0.996; p‐value .003). Stroke severity was associated with ΔMAP (B coefficient −.46, p‐value .011). Higher SBP and MAP on admission were associated with better functional outcome at three (SBP: OR 0.987; 95% CI 0.978 – 0.997; p‐value .008 ‐ MAP: OR 0.985; 95% CI 0.971 – 1; p‐value .046) and twelve (SBP: OR 0.988; 95% CI 0.979 – 0.998; p‐value .015 – MAP: OR 0.983; 95% CI 0.968 – 0.997; p‐value .02) months.

Conclusion

In this elderly population, higher BP on arrival to the emergency room (ER) and decrease in BP after the patients’ arrival to the ward were associated with improved functional outcome and reduced mortality, respectively. These results may reflect a regulatory situation in which elevated initial blood pressure indicates adequate response to cerebral tissue ischemia while subsequent blood pressure decrease instead may be a consequence of partial, successful reperfusion.
LGR5 promotes epithelial ovarian cancer proliferation, metastasis, and epithelial–mesenchymal transition through the Notch1 signaling pathway
Authors: Liu Wenxue , Zhang Jing , Gan Xupei , Shen Fangqian , Yang Xiaoming , Du Na , Xia Dandan , Liu Lei , Qiao Lianqiao , Pan Jufang , Sun Yunyan , Xi Xiaowei
Published: May 2018

Leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5) plays a vital role in the development of malignant tumors; however, its biological role and underlying mechanism in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to investigate the biological function and clinical significance of LGR5 in human EOC. We evaluated LGR5 expression in EOC cell lines and tissues from ovarian cancer patients by qPCR, Western blotting, and immunohistochemical analysis. Cell proliferation, colony formation, transwell invasion assay, and scratch‐wound assays were conducted to evaluate the expansion and invasion abilities of EOC cells. Tumor xenograft experiments were performed in female BALB/c athymic nude mice to test cell proliferation in vivo. Western blot analysis was performed to confirm the expression of epithelial‐to‐mesenchymal transition (EMT) signature proteins and their association with Notch1 signaling. The results demonstrated that LGR5 was overexpressed in EOC tissues and cell lines. Aberrant expression of LGR5 was significantly associated with patient age (P = 0.006), tumor histologic type (P < 0.001), and distant metastasis (P = 0.025). Consistent with these findings, suppression of LGR5 expression led to decreased proliferation and metastasis of EOC cell lines. Furthermore, LGR5 could induce EMT and regulate the Notch1 signaling pathway. Taken together,LGR5 may have an important role in the promotion of tumorigenesis and metastasis of EOC and is a potential therapeutic target for EOC management.
Nonmuscle myosin II in cardiac and skeletal muscle cells
Authors: Wang Jushuo , Fan Yingli , Sanger Jean M. , Sanger Joseph W.
Published: May 2018

De novoassembly of contractile myofibrils begins with the formation of premyofibrils where filaments of non‐muscle myosin (NM II), and actin organize in sarcomeric patterns with Z‐Bodies containing muscle‐specific alpha‐actinin. Interactions of muscle specific myosin (MM II) with NM II occur in a nascent myofibril stage that precedes the assembly of mature myofibrils. By the final stage of myofibrillogenesis, the only myosin II present in the mature myofibrils is MM II. In this current study of myofibril assembly, the three vertebrate isoforms of NM II (A, B, and C) and sarcomeric alpha‐actinin, ligated to GFP family proteins, were coexpressed in avian embryonic skeletal and cardiac muscle cells. Each isoform of NM II localized only in the mini‐A‐Bands of premyofibrils and nascent myofibrils. There was no evidence of localization of NM II in Z‐Bodies of premyofibrils and nascent myofibrils or in Z‐Bands of mature myofibrils. Fluorescence Recovery After Photobleaching (FRAP) experiments indicated similar exchange rates in premyofibrils for NM II isoforms A and B, whereas the IIC isoform was significantly less dynamic. Fluorescence Resonance Energy Transfer (FRET) measurements of colocalized fluorescent pairs of different NM II isoforms yielded signals similar to identical pairs, indicating copolymerization of the different NM II pairs. The role of NM II may reside in establishing the future sarcomere pattern in mature myofibrils by binding to the oppositely polarized actin filaments that extend between pairs of Z‐Bodies along premyofibrils prior to their transformation into mature myofibrils.
Immense random colocalization, revealed by automated high content image cytometry, seriously questions FISH as gold standard for detecting EML4‐ALK fusion
Authors: Smuk Gábor , Tornóczky Tamás , Pajor László , Chudoba Ilse , Kajtár Béla , Sárosi Veronika , Pajor Gábor
Published: May 2018

EML4‐ALK gene fusion (inv2(p21p23)) of non‐small cell lung cancer (NSCLC) predisposes to tyrosine kinase inhibitor treatment. One of the gold standard diagnostics is the dual color (DC) break‐apart (BA) FISH technique, however, the unusual closeness of the involved genes has been suggested to raise likelihood of random co‐localization (RCL) of signals. Although this is suspected to decrease sensitivity (often to as low as 40–70%), the exact level and effect of RCL has not been revealed thus far. Signal distances were analyzed to the 0.1 µm precision in more than 25,000 nuclei, via automated high content‐image cytometry. Negative and positive controls were created using conventional DC BA‐, and inv2(p21p23) mimicking probe‐sets, respectively. Average distance between red and green signals was 9.72 pixels (px) (±5.14px) and 3.28px (±2.44px), in positives and negatives, respectively; overlap in distribution being 41%. Specificity and sensitivity of correctly determining ALK status was 97% and 29%, respectively. When investigating inv2(p21p23) with DC BA FISH, specificity is high, but seven out of ten aberrant nuclei are inevitably falsely classified as negative, due to the extreme level of RCL. Together with genetic heterogeneity and dilution effect of non‐tumor cells in NSCLC, this immense analytical false negativity is the primary cause behind the often described low diagnostic sensitivity. These results convincingly suggest that if FISH is to remain a gold standard for detecting the therapy relevant inv(2), either a modified evaluation protocol, or a more reliable probe‐design should be considered than the current DC BA one. © 2018 International Society for Advancement of Cytometry
The indestructible insect: Velvet ants from across the United States avoid predation by representatives from all major tetrapod clades
Authors: Gall Brian G. , Spivey Kari L. , Chapman Trevor L. , Delph Robert J. , Brodie Edmund D. , Wilson Joseph S.
Published: May 2018

Velvet ants are a group of parasitic wasps that are well known for a suite of defensive adaptations including bright coloration and a formidable sting. While these adaptations are presumed to function in antipredator defense, observations between potential predators and this group are lacking. We conducted a series of experiments to determine the risk of velvet ants to a host of potential predators including amphibians, reptiles, birds, and small mammals. Velvet ants from across the United States were tested with predator's representative of the velvet ants native range. All interactions between lizards, free‐ranging birds, and a mole resulted in the velvet ants survival, and ultimate avoidance by the predator. Two shrews did injure a velvet ant, but this occurred only after multiple failed attacks. The only predator to successfully consume a velvet ant was a single American toad (Anaxyrus americanus). These results indicate that the suite of defenses possessed by velvet ants, including aposematic coloration, stridulations, a chemical alarm signal, a hard exoskeleton, and powerful sting are effective defenses against potential predators. Female velvet ants appear to be nearly impervious to predation by many species whose diet is heavily derived of invertebrate prey.
Predicting phototoxicity of alkylated PAHs, mixtures of PAHs, and water accommodated fractions (WAF) of neat and weathered petroleum with the phototoxic target lipid model
Authors: Marzooghi Solmaz , Finch Bryson E. , Stubblefield William A. , Di Toro Dominic M.
Published: May 2018

The toxicity of petroleum can increase considerably after exposure to solar radiation, during which certain components in the mixture, including polycyclic aromatic hydrocarbons (PAHs), absorb light in ultraviolet and visible portions of the solar radiation spectrum. A phototoxic target lipid model (PTLM), previously developed to predict the phototoxicity of single PAHs, is validated for 4 species (Americamysis bahia, Rhepoxynius abronius, Daphnia magna, and Pimephales promelas) exposed to 12 compounds that are components of petroleum, including alkylated PAHs and dibenzothiophene. The PTLM is also used to predict the phototoxicity of binary and ternary mixtures of 3 PAHs, pyrene, anthracene, and fluoranthene, to A. bahia and Menidia beryllina. Finally, it is used to predict the toxicity of water accommodated fractions of neat and naturally weathered Macondo crude oil samples from the Deepwater Horizon oil spill sites. The Gulf of Mexico species, including A. bahia, M. beryllina, Cyprinodon variegatus, and Fundulus grandis were exposed to the oil samples under natural and simulated solar radiation. The results support the applicability of the PTLM for predicting the phototoxicity of petroleum. Environ Toxicol Chem 2018;37:2165–2174. © 2018 SETAC.
FishGen.net: An Online Genetic Repository for Salmon and Steelhead Genetic Baselines
Authors: McCane Jesse , Adam Chris , Fleming Bill , Bricker Mark , Campbell Matthew R
Published: May 2018

FishGen is a final repository for Pacific salmon Oncorhynchus spp. and steelhead O. mykiss genetic data generated as part of the genetic stock identification and parentage-based tagging projects in the Columbia River basin and throughout the Pacific Coast of North America. Resource Data, Inc., developed this web-based, GIS-interfaced software, which is freely available to the public, with funding from the Pacific Coastal Salmon Recovery Fund and Bonneville Power Administration. FishGen currently houses genetic stock identification baselines for both Chinook Salmon O. tshawytscha and steelhead in the Columbia and Snake river basins, as well as hatchery, parentage-based, tagging baselines for both species in the Snake River basin. Because it has a user-friendly interface and protocol for submitting and storing standardized genetic and sample metadata, it is an excellent tool for supporting genetic research and monitoring projects throughout the region.
Tools for work‐up and prepurification of tritium‐labeled small molecules
Authors: Muri Dieter , Edelmann Martin R.
Published: May 2018

This practitioner protocol describes the use and application of different types of solid‐phase extractions and metal scavengers for small‐scale reactions, particularly in the context of purifying tritiated molecules from heavily contaminated reaction mixtures. Polymer‐bound strong cation exchangers are especially suitable for separating basic compounds from neutral or acidic molecules and have been widely applied in the work‐up of iridium‐based hydrogen isotope exchange reactions. Polymer‐bound strong anion exchangers can help to separate acidic compounds from their neutral or basic counterparts or to easily convert a trifluoroacetate or formate salt to its free base after HPLC purification. Metal scavengers have been used for the work‐up of metal‐catalyzed coupling reactions and hydrogen isotope exchange reactions, facilitating subsequent chromatographic purifications.
Cost‐efficient magnetic nanoporous carbon derived from citrus peel for the selective adsorption of seven insecticides
Authors: Zhou Yuantao , Cao Shurui , Xi Cunxian , Chen Jiuyan , Zhang Lei , Li Xianliang , Wang Guomin , Chen Zhiqiong
Published: May 2018

A magnetic solid‐phase extraction adsorbent that consisted of citrus peel‐derived nanoporous carbon and silica‐coated Fe3O4 microspheres (C/SiO2@Fe3O4) was successfully fabricated by co‐precipitation. As a modifier for magnetic microspheres, citrus peel‐derived nanoporous carbon was not only economical and renewable for its raw material, but exerted enormous nanosized pore structure, which could directly influence the type of adsorbed analytes. The C/SiO2@Fe3O4 also possessed the advantages of Fe3O4 microspheres like superparamagnetism, which could be easily separated magnetically after adsorption. Integrating the superior of biomass‐derived nanoporous carbon and Fe3O4 microspheres, the as‐prepared C/SiO2@Fe3O4 showed high extraction efficiency for target analytes. The obtained material was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, and the Brunauer–Emmett–Teller method, which demonstrated that C/SiO2@Fe3O4 was successfully synthesized. Under the optimal conditions, the adsorbent was selected for the selective adsorption of seven insecticides before gas chromatography with mass spectrometry detection, and good linearity was obtained in the concentration range of 2–200 μg/kg with the correlation coefficient ranging from 0.9952 to 0.9997. The limits of detection were in the range of 0.03–0.39 μg/kg. The proposed method has been successfully applied to the enrichment and detection of seven insecticides in real vegetable samples.