bluuebunny/crossref_metadata_2025 huggingface dataset:
Chlorophyll Fluorescence Better Captures Seasonal and Interannual Gross Primary Productivity Dynamics Across Dryland Ecosystems of Southwestern North America
Authors: Smith W. K. , Biederman J. A. , Scott R. L. , Moore D. J. P. , He M. , Kimball J. S. , Yan D. , Hudson A. , Barnes M. L. , MacBean N. , Fox A. M. , Litvak M. E.
Published: January 2018

Satellite remote sensing provides unmatched spatiotemporal information on vegetation gross primary productivity (GPP). Yet understanding of the relationship between GPP and remote sensing observations and how it changes with factors such as scale, biophysical constraint, and vegetation type remains limited. This knowledge gap is especially apparent for dryland ecosystems, which have characteristic high spatiotemporal variability and are under‐represented by long‐term field measurements. Here we utilize an eddy covariance (EC) data synthesis for southwestern North America in an assessment of how accurately satellite‐derived vegetation proxies capture seasonal to interannual GPP dynamics across dryland gradients. We evaluate the enhanced vegetation index, solar‐induced fluorescence (SIF), and the photochemical reflectivity index. We find evidence that SIF is more accurately capturing seasonal GPP dynamics particularly for evergreen‐dominated EC sites and more accurately estimating the full magnitude of interannual GPP dynamics for all dryland EC sites. These results suggest that incorporation of SIF could significantly improve satellite‐based GPP estimates.
Effects of Ensemble Configuration on Estimates of Regional Climate Uncertainties
Authors: Goldenson N. , Mauger G. , Leung L. R. , Bitz C. M. , Rhines A.
Published: January 2018

Internal variability in the climate system can contribute substantial uncertainty in climate projections, particularly at regional scales. Internal variability can be quantified using large ensembles of simulations that are identical but for perturbed initial conditions. Here we compare methods for quantifying internal variability. Our study region spans the west coast of North America, which is strongly influenced by El Niño and other large‐scale dynamics through their contribution to large‐scale internal variability. Using a statistical framework to simultaneously account for multiple sources of uncertainty, we find that internal variability can be quantified consistently using a large ensemble or an ensemble of opportunity that includes small ensembles from multiple models and climate scenarios. The latter also produce estimates of uncertainty due to model differences. We conclude that projection uncertainties are best assessed using small single‐model ensembles from as many model‐scenario pairings as computationally feasible, which has implications for ensemble design in large modeling efforts.
Discovery of 1 Hz Range Modulation of Isolated Proton Aurora at Subauroral Latitudes
Authors: Ozaki M. , Shiokawa K. , Miyoshi Y. , Kataoka R. , Connors M. , Inoue T. , Yagitani S. , Ebihara Y. , Jun C.‐W. , Nomura R. , Sakaguchi K. , Otsuka Y. , Uchida H. A. , Schofield I. , Danskin D. W.
Published: January 2018

Isolated proton aurora (IPA) is a manifestation of the wave‐particle interaction visible at subauroral latitudes, with activity on many timescales. We herein present the first observational evidence of rapid luminous modulation of IPA correlated with simultaneously observed Pc1 waves observed on the ground, which are equivalent to the electromagnetic ion cyclotron (EMIC) waves in the magnetosphere. The fastest luminous modulation of IPA was observed in the 1 Hz frequency range, which was twice the frequency of the related Pc1 waves. The time lag between variations of Pc1 wave power and the IPA luminosity suggests that the source regions of IPA are distributed near the magnetic equator, suggesting an EMIC wave‐energetic (a few tens of keV) proton or relativistic (MeV or sub‐MeV) electron interaction. The generation mechanism of this 1 Hz luminous modulation remains an open issue, but this study supports the importance of nonlinear pitch angle scattering via wave‐particle interactions.
Discrete Light Spectrum of Complex‐Shaped Meta‐atoms
Authors: Silva Solange , Morgado Tiago A. , Silveirinha Mário G.
Published: January 2018

We investigate the potentials of open plasmonic resonators (meta‐atoms) with different shapes in the context of light trapping. Consistent with the theory of Silveirinha (2014), it is found that in some conditions complex‐shaped dielectric cavities may support discrete light states screened by volume plasmons that in the limit of vanishing material loss have an infinite lifetime. The embedded eigenstates can be efficiently pumped with a plane wave excitation when the meta‐atom core has a nonlinear response, such that the trapped light energy is precisely quantized.
A Bayesian Hierarchical Approach to Multivariate Nonstationary Hydrologic Frequency Analysis
Authors: Bracken C. , Holman K. D. , Rajagopalan B. , Moradkhani H.
Published: January 2018

We present a general Bayesian hierarchical framework for conducting nonstationary frequency analysis of multiple hydrologic variables. In this, annual maxima from each variable are assumed to follow a generalized extreme value (GEV) distribution in which the location parameter is allowed to vary in time. A Gaussian elliptical copula is used to model the joint distribution of all variables. We demonstrate the utility of this framework with a joint frequency analysis model of annual peak snow water equivalent (SWE), annual peak flow, and annual peak reservoir elevation at Taylor Park dam in Colorado, USA. Indices of large‐scale climate drivers—El Niño Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), and Atlantic Multidecadal Oscillation (AMO) are used as covariates to model temporal nonstationarity. The Bayesian framework provides the posterior distribution of the model parameters and consequently the return levels. Results show that performing a multivariate joint frequency analysis reduces the uncertainty in return level estimates and better captures multivariate dependence compared to an independent model.
Presence versus Proximity: The Role of Pendant Amines in the Catalytic Hydrolysis of a Nerve Agent Simulant
Authors: Islamoglu Timur , Ortuño Manuel A. , Proussaloglou Emmanuel , Howarth Ashlee J. , Vermeulen Nicolaas A. , Atilgan Ahmet , Asiri Abdullah M. , Cramer Christopher J. , Farha Omar K.
Published: January 2018

Amino‐functionalized zirconium‐based metal‐organic frameworks (MOFs) have shown unprecedented catalytic activity compared to non‐functionalized analogues for hydrolysis of organophosphonate‐based toxic chemicals. Importantly, the effect of the amino group on the catalytic activity is significantly higher in the case of UiO‐66‐NH2, where the amino groups reside near the node, compared to UiO‐67‐m‐NH2, where they are directed away from the node. Herein, we show that the proximity of the amino group is crucial for fast catalytic activity towards hydrolysis of organophosphonate‐based nerve agents. The generality of the observed amine‐proximity‐dictated catalytic activity has been tested on two different MOF systems which have different topology. DFT calculations reveal that amino groups on all the MOFs studied are not acting as Brønsted bases; instead they control the microsolvation environment at the Zr6‐node active site and therefore increase the overall catalytic rates.
The Solution of the Puzzle of Smectic‐Q: The Phase Structure and the Origin of Spontaneous Chirality
Authors: Lu Huanjun , Zeng Xiangbing , Ungar Goran , Dressel Christian , Tschierske Carsten
Published: January 2018

The so‐called smectic‐Q (SmQ) liquid crystal phase was discovered in 1983 in rod‐like molecules, but its structure remain unclear in spite of numerous attempts to solve it. Herein, we report what we believe to be the solution: A unique bicontinuous phase that is non‐cubic and is made up of orthogonal twisted columns with planar 4‐way junctions. While SmQ had only been observed in chiral compounds, we show that this chiral phase forms also in achiral materials through spontaneous symmetry breaking. The results strongly support the idea of a helical substructure of bicontinuous phases and long‐range homochirality being sustained by helicity‐matching at network junctions. The model also explains the triangular shape of double‐gyroid domains growing within a SmQ environment. SmQ‐forming materials hold potential for applications such as circularly polarized light emitters that require no alignment or asymmetric synthesis.
An Expanded Porphycene with High NIR Absorptivity That Stabilizes Two Different Kinds of Metal Complexes
Authors: Anguera Gonzalo , Cha Won‐Young , Moore Matthew D. , Brewster James T. , Zhao Michael Y. , Lynch Vincent D. , Kim Dongho , Sessler Jonathan L.
Published: January 2018

A new expanded porphycene with 26 π‐electrons has been prepared by the McMurry coupling of 1,4‐bis(3,4‐diethyl‐2‐pyrryl)benzene dialdehyde. Expansion of the porphycene framework provides a ligand capable of stabilizing a bis(rhodium) and a monoruthenium complex. These new porphycene derivatives absorb strongly in the NIR spectral region, with appreciable absorptivity up to 1300 nm. On the basis of their ground‐ and excited‐state spectroscopic features and structural parameters, both the free‐base system and the bis(rhodium) complex are considered to be Hückel‐type aromatic systems. This conclusion is supported by DFT calculations.
SuFEx Chemistry of Thionyl Tetrafluoride (SOF4) with Organolithium Nucleophiles: Synthesis of Sulfonimidoyl Fluorides, Sulfoximines, Sulfonimidamides, and Sulfonimidates
Authors: Gao Bing , Li Suhua , Wu Peng , Moses John E. , Sharpless K. Barry
Published: January 2018

Thionyl tetrafluoride (SOF4) is a valuable connective gas for sulfur fluoride exchange (SuFEx) click chemistry that enables multidimensional linkages to be created via sulfur–oxygen and sulfur–nitrogen bonds. Herein, we expand the available SuFEx chemistry of SOF4 to include organolithium nucleophiles, and demonstrate, for the first time, the controlled projection of sulfur–carbon links at the sulfur center of SOF4‐derived iminosulfur oxydifluorides (R1−N=SOF2). This method provides rapid and modular access to sulfonimidoyl fluorides (R1−N=SOFR2), another array of versatile SuFEx connectors with readily tunable reactivity of the S−F handle. Divergent connections derived from these valuable sulfonimidoyl fluoride units are also demonstrated, including the synthesis of sulfoximines, sulfonimidamides, and sulfonimidates.
Influence of study approaches and course design on academic success in the undergraduate anatomy laboratory
Authors: Eleazer Courtney D. , Scopa Kelso Rebecca
Published: January 2018

Many pre‐health professional programs require completion of an undergraduate anatomy course with a laboratory component, yet grades in these courses are often low. Many students perceive anatomy as a more challenging subject than other coursework, and the resulting anxiety surrounding this perception may be a significant contributor to poor performance. Well‐planned and deliberate guidance from instructors, as well as thoughtful course design, may be necessary to assist students in finding the best approach to studying for anatomy. This article assesses which study habits are associated with course success and whether course design influences study habits. Surveys (n = 1,274) were administered to students enrolled in three undergraduate human anatomy laboratory courses with varying levels of cooperative learning and structured guidance. The surveys collected information on potential predictors of performance, including student demographics, educational background, self‐assessment ability, and study methods (e.g., flashcards, textbooks, diagrams). Compared to low performers, high performers perceive studying in laboratory, asking the instructor questions, quizzing alone, and quizzing others as more effective for learning. Additionally, students co‐enrolled in a flipped, active lecture anatomy course achieve higher grades and find active learning activities (e.g., quizzing alone and in groups) more helpful for their learning in the laboratory. These results strengthen previous research suggesting that student performance is more greatly enhanced by an active classroom environment thatpracticessuccessful study strategies rather than one that simplyencouragesstudents to employ such strategies inside and outside the classroom. Anat Sci Educ 11: 496–509. © 2018 American Association of Anatomists.
Determination of cycloserine in microdialysis samples using liquid chromatography–tandem mass spectrometry with benzoyl chloride derivatization
Authors: Zhang Wenjing , Wan Sihui , Chen Lizhi , Wang Xuebin , Wang Zhuo , Huang Yi
Published: January 2018

A new method for the analysis of cycloserine (4‐amino‐3‐isoxazolidinone, CYC) in rat microdialysis samples has been developed. This method consists of derivatizing the CYC with benzoyl chloride, which transforms primary amines into highly stable derivatives. An attractive feature of this method was that the derivatization reaction is straightforward and can be completed within 10 min. The formed derivative, in contrast to the non‐derivatized analyte, exhibited increased chromatographic retention and decreased matrix effects resulting from the co‐elution of other components using reversed‐phase liquid chromatography and on‐line switching. Detection on a quadrupole–linear ion trap mass spectrometer (AB3200 Q‐Trap) was performed using electrospray tandem mass spectrometry in multiple reaction monitoring mode. Various derivatization parameters were optimized in order to improve chromatographic separation and minimize ion suppression. In particular, the benzoylation reaction was improved to enhance the reproducibility and sensitivity of the chromatographic method. The transition m/z 207.1 → 105.1 was acquired to monitor the CYC derivatization products. The method was fully validated for its sensitivity, selectivity, matrix effect and stability. A good linearity over the selected range (r > 0.99, range = 22–2200 mg/L), as well as accuracy and precision within ±7% of the target values, was obtained. The assay described herein was successfully applied to quantitatively measure CYC in the lung and blood of anesthetized rats.
Preparation of an injectable doxorubicin surface modified cellulose nanofiber gel and evaluation of its anti‐tumor and anti‐metastasis activity in melanoma
Authors: Alizadeh Najmeh , Akbari Vajihe , Nurani Maryam , Taheri Azade
Published: January 2018

Cellulose nanofibers (Cel‐NFs) gel can be considered as a useful drug carrier because of its biocompatibility, high specific surface area, and high loading capacity of drugs. Injectable Cel‐NFs gel could deliver doxorubicin (DOX) for localized chemotherapy of melanoma and suppress melanoma cells migration because of the physical barrier property of Cel‐NFs. We prepared DOX surface modified Cel‐NFs (DOX‐Cel‐NFs) gel by the electrostatic attachment of DOX molecules on the surface of Cel‐NFs. The increase in the zeta potential of nanofibers and the changes in the FTIR spectra of DOX‐Cel‐NFs compared to Cel‐NFs proved this attachment. DOX‐Cel‐NFs showed nano‐fibrous structure with an average diameter of 22.32 ± 10.66 nm after analyzing using field emission scanning electron microscopy. The suitable injectability of DOX‐Cel‐NFs gel verified its promising application for the localized chemotherapy. DOX‐Cel‐NFs gel exhibited a sustained drug release manner. The cytotoxicity results showed that DOX‐Cel‐NFs were more cytotoxic against melanoma cancer cells than the free DOX during 48 h incubation period. Moreover, DOX‐Cel‐NFs gel can suppress the melanoma cancer cells migration efficiently. Thus our results emphasize the potential of DOX‐Cel‐NFs gel as a chemotherapeutic agent for local delivery of DOX in order to treat melanoma and prevent its metastasis. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:537–545, 2018
Online measurement of the respiratory activity in shake flasks enables the identification of cultivation phases and patterns indicating recombinant protein production in various Escherichia coli host strains
Authors: Ihling Nina , Bittner Natalie , Diederichs Sylvia , Schelden Maximilian , Korona Anna , Höfler Georg Theo , Fulton Alexander , Jaeger Karl‐Erich , Honda Kohsuke , Ohtake Hisao , Büchs Jochen
Published: January 2018

Escherichia coli is commonly used for recombinant protein production with many available host strains. Screening experiments are often performed in batch mode using shake flasks and evaluating only the final product concentration. This conventional approach carries the risk of missing the best strain due to limited monitoring capabilities. Thus, this study focuses on investigating the general suitability of online respiration measurement for selecting expression hosts for heterologous protein production. The oxygen transfer rate (OTR) for different T7‐RNA polymerase‐dependent Escherichia coli expression strains was compared under inducing and noninducing conditions. As model enzymes, a lipase A from Bacillus subtilis (BSLA) and a 3‐hydroxybutyryl‐CoA dehydrogenase from Thermus thermophilus (HBD) were chosen. Four strains were compared during expression of both enzymes in autoinduction medium. Additionally, four strains were compared during expression of the BSLA with IPTG induction. It was found that the metabolic burden during recombinant protein production induces a phase of constant OTR, while undisturbed cell growth with no or little product formation is indicated by an exponential increase. This pattern is independent of the host strain, expressed enzyme, and induction method. Furthermore, the OTR gives information about carbon source consumption, biomass formation, and the transition from production to noninduced second growth phase, thereby ensuring a fair comparison of different strains. In conclusion, online monitoring of the respiration activity is suited to qualitatively identify, if a recombinant protein is produced by a strain or not. Furthermore, laborious offline sampling is avoided. Thus, the technique is easier and faster compared to conventional approaches. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:315–327, 2018
Leveraging single‐pass tangential flow filtration to enable decoupling of upstream and downstream monoclonal antibody processing
Authors: Brinkmann Alex , Elouafiq Sanaa , Pieracci John , Westoby Matthew
Published: January 2018

Decoupling upstream and downstream operations in biopharmaceutical production could enable more flexible manufacturing operations and could allow companies to leverage strategic or financial benefits that would be otherwise unattainable. A decoupling process was developed and scaled up utilizing single‐pass tangential flow filtration for volume reduction, followed by bulk freezing in single‐use bags prior to purification. Single‐pass tangential flow filtration can be used to continuously concentrate harvested cell culture fluid, reducing the volume by 15‐25× with a step yield of >96%. These concentration factors were reproduced with a second product, indicating that the process could be amenable to platform processes. Experimental data indicate that the product tested was stable for at least one year at −40 or −70°C. The concentration of the harvested cell culture fluid—either with or without a subsequent period of frozen storage—had no impact on the product quality attributes that were tested. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:405–411, 2018
Characterizing the fluid dynamics of the inverted frustoconical shaking bioreactor
Authors: Zhu Likuan , Zhang Xueting , Cheng Kai , Lv Zhonghua , Zhang Lei , Meng Qingyong , Yuan Shujie , Song Boyan , Wang Zhenlong
Published: January 2018

The authors conducted a three‐dimensional computational fluid dynamics (CFD) simulation to calculate the flow field in the inverted frustoconical shaking bioreactor with 5 L working volume (IFSB‐5L). The CFD models were established for the IFSB‐5L at different operating conditions (different shaking speeds and filling volumes) and validated by comparison of the liquid height distribution in the agitated IFSB‐5L. The “out of phase” operating conditions were characterized by analyzing the flow field in the IFSB‐5L at different filling volumes and shaking speeds. The values of volumetric power consumption (P/VL) and volumetric mass transfer coefficient (kLa) were determined from simulated and experimental results, respectively. Finally, the operating condition effect on P/VL and kLa was investigated. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:478–485, 2018
HPV‐16 targeted DNA vaccine expression: The role of purification
Authors: Almeida Ana M. , Tomás Joana , Pereira Patrícia , Queiroz João A. , Sousa Fani , Sousa Ângela
Published: January 2018

DNA vaccines have come to light in the last decades as an alternative method to prevent many infectious diseases, but they can also be used for the treatment of specific diseases, such as cervical cancer caused by Human Papillomavirus (HPV). This virus produces E6 and E7 oncoproteins, which alter the cell cycle regulation and can interfere with the DNA repairing system. These features can ultimately lead to the progression of cervical cancer, after cell infection by HPV. Thus, the development of a DNA vaccine targeting both proteins arises as an interesting option in the treatment of this pathology. Nonetheless, before evaluating its therapeutic potential, the purity levels of a biopharmaceutical must meet the regulatory agency specifications. Previously, our research group successfully purified the supercoiled isoform of the recombinant HPV‐16 E6/E7 DNA vaccine with virtual 100% purity by affinity chromatography. The present work was designed to evaluate the effect that pDNA sample purity levels may exert in the expression of a target protein. Thus, in vitro studies were performed to assess the vaccine ability to produce the target proteins and to compare the expression efficiency between the pDNA sample obtained by affinity chromatography, which only presents the sc isoform and fulfils the regulatory agency recommendations, and the same DNA vaccine retrieved by a commercial purification kit, which contains different pDNA isoforms. Our achievements suggest that the E6/E7 DNA vaccine purified by affinity chromatography promotes higher E6 and E7 mRNA and protein expression levels than the DNA vaccine purified with the commercial kit. Overall, these results underline the importance that a purification strategy may present in the therapeutic outcome of recombinant DNA vaccines, envisaging their further application as biopharmaceuticals. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:546–551, 2018
Ectopic expression of EuWRI1, encoding a transcription factor in E. ulmoides, changes the seeds oil content in transgenic tobacco
Authors: Wang Lu , Du Xilong , Feng Yanzhi , Liu Panfeng , Zhu Jingle , Zhang Lin , Du Hongyan , Ma Mingguo , Li Fangdong
Published: January 2018

The WRINKLED1 (WRI1) gene is a well‐established key transcriptional regulator involved in the regulation of fatty acid biosynthesis in developing seeds. In this study, a new WRI1 gene was isolated from seeds of Eucommia ulmoides and named EuWRI1. A close link between gibberellins signaling and EuWRI1 gene expression was suggested in this study. Functional characterization of EuWRI1 was elucidated through seed‐specific expression in tobacco. In transgenic tobacco, the expression of EuWRI1 in eight independent transgenic lines was detected by semiquantitative RT‐PCR. The relative mRNA accumulation of genes encoding enzymes involved in fatty acid biosynthesis (biotin carboxyl carrier protein and keto‐ACP synthase 1) was also assayed in tobacco seeds. Analysis of the seeds oil content and starch content indicated that the transgenic lines showed a significant increase in seeds oil content, whereas starch content decreased significantly. Further analysis of the fatty acid composition revealed that palmitic acid (16:0), linoleic acid (18:2) and linolenic acid (18:3) increased significantly in seeds of transgenic tobacco lines, but stearic acid (18:0) levels significantly declined. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:337–346, 2018
Protein A chromatography resin lifetime—impact of feed composition
Authors: Pathak Mili , Rathore Anurag S. , Lintern Katherine , Bracewell Daniel G.
Published: January 2018

Adsorbent lifetime during protein A chromatography is not readily predicted or understood, representing a key challenge to be addressed for biopharmaceutical manufacturers. This article focuses on the impact of feed composition on the performance of a typical agarose‐based protein A resin across a lifetime of 50 cycles. Cycling studies were performed using three different feed materials with varying levels of feed components including proteases, histones, DNA, and nonhistone proteins. Changes in the process and quality attributes were measured. The DBCs were not seen to vary between conditions although there was a reduction in particle porosity in all cases. Fluorescence spectroscopy and LC‐MS/MS were used to identify the contribution and extent of fouling to the observed capacity loss. Residual protein A ligand density and deposition of foulants (HCP, residual mAb, and DNA) varied between the three feed materials. Resins cycled in feed materials containing high concentrations of HCP and histones were seen to have greater extents of capacity loss. The mode of performance loss, capacity loss, or impact on product quality was seen to vary depending on the feed material. The results indicate that feed material composition may be correlated to the rate and mode of resin aging as a basis for improved process understanding. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:412–419, 2018
Identification of the Biosynthetic Gene Cluster for Himeic Acid A: A Ubiquitin‐Activating Enzyme (E1) Inhibitor in Aspergillus japonicus MF275
Authors: Hashimoto Makoto , Kato Hikaru , Katsuki Ayako , Tsukamoto Sachiko , Fujii Isao
Published: January 2018

Himeic acid A, which is produced by the marine fungus Aspergillus japonicus MF275, is a specific inhibitor of the ubiquitin‐activating enzyme E1 in the ubiquitin–proteasome system. To elucidate the mechanism of himeic acid biosynthesis, feeding experiments with labeled precursors have been performed. The long fatty acyl side chain attached to the pyrone ring is of polyketide origin, whereas the amide substituent is derived from leucine. These results suggest that a polyketide synthase–nonribosomal peptide synthase (PKS‐NRPS) is involved in himeic acid biosynthesis. A candidate gene cluster was selected from the results of genome sequencing analysis. Disruption of the PKS‐NRPS gene by Agrobacterium‐mediated transformation confirms that HimA PKS‐NRPS is involved in himeic acid biosynthesis. Thus, the him biosynthetic gene cluster for himeic acid in A. japonicus MF275 has been identified.
A Nanocrystalline POM@MOFs Catalyst for the Degradation of Phenol: Effective Cooperative Catalysis by Metal Nodes and POM Guests
Authors: Zhong Xiahua , Lu Ying , Luo Fang , Liu Yiwei , Li Xiaohui , Liu Shuxia
Published: January 2018

Crystalline POM@MOFs hybrids are very promising for catalysis, due to catalytically active polyoxometalates (POMs) dispersed at the molecular level, and enhanced stability of both POMs and metal‐organic frameworks (MOFs). Herein, PW12 was encapsulated into MOF HKUST‐1 through a facile liquid‐assisted grinding method, and the obtained [Cu2(BTC)4/3(H2O)2]6[HPW12O40] (BTC=1,2,3‐benzenetricarboxylic acid) nanocrystals (NENU‐3N) were applied as catalysts in the degradation of phenol. It is the first time that liquid‐assisted grinding was applied in the preparation of nanocrystalline POM@MOFs hybrids. The NENU‐3N nanocrystals catalyzed the degradation of phenol on the basis of both MOF and POM catalytic activities, representing the first example of POM@MOFs catalyst boosting catalytic oxidation reaction with double actives sites. Strikingly, up to 97 % conversion and 88 % mineralization have successfully realized by perfect cooperative catalysis between POMs and CuII nodes in MOFs at 35 °C. Moreover, comparative experiments suggest that the reduced size of NENU‐3N catalyst is beneficial for improving its catalytic performance. Finally, the nanocrystalline NENU‐3N catalyst possesses high stability, which can be easily recovered and reused 5 times without loss of catalytic activity.
On the Field Relevance of Negative Lug Corrosion by Micro‐Hybrid Operation Mode in the Vehicle
Authors: Börger Alexander , Keil Sabrina Nadine
Published: January 2018

Bei Bleibatterien mit nicht festgelegter Batteriesäure (sog. Nassbatterien) ist vor geraumer Zeit das Auftreten eines neuen Schädigungsmechanismus beschrieben worden, die Abkorrosion negativer Stromableiter. Diese kann unter Laborbedingungen durch artifizielle Pulsfolgen erzeugt werden, die mit einer hohen Strombelastung einhergehen. Die Messergebnisse an Starterbatterien mit Referenzelektroden und echten Start‐Pulsen im Fahrzeug werden kontrastiert und lassen nicht den Schluss zu, dass es bei Start‐Stopp‐Betrieb tatsächlich zu vermehrter negativer Fahnenkorrosion kommen sollte.
Controlling the error on target motion through real‐time mesh adaptation: Applications to deep brain stimulation
Authors: Bui Huu Phuoc , Tomar Satyendra , Courtecuisse Hadrien , Audette Michel , Cotin Stéphane , Bordas Stéphane P.A.
Published: January 2018

An error‐controlled mesh refinement procedure for needle insertion simulations is presented. As an example, the procedure is applied for simulations of electrode implantation for deep brain stimulation. We take into account the brain shift phenomena occurring when a craniotomy is performed. We observe that the error in the computation of the displacement and stress fields is localised around the needle tip and the needle shaft during needle insertion simulation. By suitably and adaptively refining the mesh in this region, our approach enables to control, and thus to reduce, the error whilst maintaining a coarser mesh in other parts of the domain. Through academic and practical examples we demonstrate that our adaptive approach, as compared with a uniform coarse mesh, increases the accuracy of the displacement and stress fields around the needle shaft and, while for a given accuracy, saves computational time with respect to a uniform finer mesh. This facilitates real‐time simulations. The proposed methodology has direct implications in increasing the accuracy, and controlling the computational expense of the simulation of percutaneous procedures such as biopsy, brachytherapy, regional anaesthesia, or cryotherapy. Moreover, the proposed approach can be helpful in the development of robotic surgeries because the simulation taking place in the control loop of a robot needs to be accurate, and to occur in real time.
Investigating Protein–Ligand Interactions by Solution Nuclear Magnetic Resonance Spectroscopy
Authors: Becker Walter , Bhattiprolu Krishna Chaitanya , Gubensäk Nina , Zangger Klaus
Published: January 2018

Protein–ligand interactions are of fundamental importance in almost all processes in living organisms. The ligands comprise small molecules, drugs or biological macromolecules and their interaction strength varies over several orders of magnitude. Solution NMR spectroscopy offers a large repertoire of techniques to study such complexes. Here, we give an overview of the different NMR approaches available. The information they provide ranges from the simple information about the presence of binding or epitope mapping to the complete 3 D structure of the complex. NMR spectroscopy is particularly useful for the study of weak interactions and for the screening of binding ligands with atomic resolution.
How to Consider Rare Genetic Variants in Personalized Drug Therapy
Authors: Lauschke Volker M. , Ingelman‐Sundberg Magnus
Published: January 2018

Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug‐metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME). In addition, genetic variation in factors encoding the major histocompatibility complex have been helpful to predict immune‐mediated drug toxicity. This knowledge has been translated into clinical applications through the implementation of pharmacogenomic biomarkers. Over 230 of such markers that can, to a certain extent, predict drug efficacy or the likelihood of adverse drug reactions (ADRs) are recognized by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and are included in the drug labels of the respective medication. They are of particular value in cancer therapy to provide information of use to avoid ADRs and lack of response.
Different in vitro and in vivo tools for elucidating the human metabolism of alpha‐cathinone‐derived drugs of abuse
Authors: Manier Sascha K. , Richter Lilian H.J. , Schäper Jan , Maurer Hans H. , Meyer Markus R.
Published: January 2018

In vitro and in vivo experiments are widely used for studying the metabolism of new psychoactive substances (NPS). The availability of such data is required for toxicological risk assessments and development of urine screening approaches. This study investigated the in vitro metabolism of the 5 pyrrolidinophenone‐derived NPS alpha‐pyrrolidinobutyrophenone (alpha‐PBP), alpha‐pyrrolidinopentiothiophenone (alpha‐PVT), alpha‐pyrrolidinohexanophenone (alpha‐PHP), alpha‐pyrrolidinoenanthophenone (alpha‐PEP, PV8), and alpha‐pyrrolidinooctanophenone (alpha‐POP, PV9). First, they were incubated with pooled human liver microsomes (pHLM) or pooled human liver S9 fraction (pS9) for identification of the main phase I and II metabolites. All substances formed hydroxy metabolites and lactams. Longer alkyl chains resulted in keto group and carboxylic acid formation. Comparing these results with published data obtained using pHLM, primary human hepatocytes (PHH), and authentic human urine samples, PHH provided the most extensive metabolism. Second, enzyme kinetic studies showed that the initial metabolic steps were formed by cytochrome P450 isoforms (CYP) CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 resulting in pyrrolidine, thiophene or alkyl hydroxy metabolites depending on the length of the alkyl chain. The kinetic parameters indicated an increasing affinity of the CYP enzymes with increase of the length of the alkyl chain. These parameters were then used to calculate the contribution of a single CYP enzyme to the in vivo hepatic clearance. CYP2C19 and CYP2D6 were mainly involved in the case of alpha‐PBP and CYP1A2, CYP2C9 and CYP2C19 in the case of alpha‐PVT, alpha‐PHP, alpha‐PEP, and alpha‐POP.
Keratinous matrices for the assessment of drugs of abuse consumption: A correlation study between hair and nails
Authors: Cappelle Delphine , De Keukeleire Steven , Neels Hugo , Been Frederic , De Doncker Mireille , Dom Geert , Crunelle Cleo L. , Covaci Adrian , van Nuijs Alexander L.N.
Published: January 2018

Keratinous matrices – hair and nails – accumulate substances over time and allow retrospective investigation of past consumption. Analysis of these matrices can provide information complementary to blood and urine analysis or can be used as standalone. So far, research has primarily focused on the detection of substances in hair, while studies in nails are scarce. In this study, we assessed concentrations of drugs of abuse and their metabolites in hair, fingernails, and toenails collected from the same individuals to evaluate differences and correlations between matrices. A total of 26 hair, 24 fingernail, and 18 toenail samples were collected. Samples were analysed by a validated liquid chromatography–tandem mass spectrometry method able to simultaneously detect the following compounds: amphetamine (AMP), methamphetamine, 3,4‐methylenedioxymethamphetamine (MDMA), 3,4‐methylenedioxyethylamphetamine, morphine (MOR), codeine (COD), 6‐monoacetylmorphine (6‐MAM), methadone (MTD), 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP), cocaine (COC), benzoylecgonine (BE), and ecgonine methyl ester (EME). Strong positive correlations between hair, fingernails, and toenails were present for COC, BE, EME, AMP and MDMA. MOR, COD, 6‐MAM, MTD and EDDP showed positive trends. Concentrations were generally higher in nails compared to hair. Ratios between parent compounds and their metabolites were assessed for 6‐MAM/MOR, EDDP/MTD, BE/COC and EME/COC. Preliminary cut‐off concentrations for COC, BE, EME and AMP in fingernails and toenails were proposed. In light of these results, nails can be considered as a useful alternative to hair for monitoring of long‐term drug consumption. However, care should be taken regarding the variability in the accumulation of compounds between the matrices.
Regulators of spindle microtubules and their mechanisms: Living together matters
Authors: Lakshmi R. Bhagya , Nair Vishnu M. , Manna Tapas K.
Published: January 2018

Development and survival of all eukaryotic organisms depend on equal partitioning of their chromosomes between the two newly formed daughter cells during mitosis. The mitotic spindle performs the task of physically segregating the chromosomes through multiple stages of mitosis. During this process, kinetochore‐microtubule attachment requires to be selectively stabilized to hold the chromosomes, but at the same time, it has to be flexible enough to allow kinetochore microtubule dynamicity and chromosome movements. Research during the last decade or so has identified a number of proteins associated with the spindle microtubule plus ends that regulate these processes and orchestrate forces to spatially organize and separate the chromosomes. In this review, we describe the molecular details of those regulators and their mechanisms of action at the kinetochore‐microtubule interface. © 2018 IUBMB Life, 70(2):101–111, 2018
Rapid determination of carbendazim in complex matrices by electrospray ionization mass spectrometry with syringe filter needle
Authors: Yang Bi‐cheng , Wan Xi‐di , Yang Xiao , Li Yun‐jun , Zhang Zi‐yu , Wan Xiao‐ju , Luo Yong , Deng Wei , Wang Feng , Huang Ou‐ping
Published: January 2018

The determination of pesticide residues is an indispensable task in controlling food safety and environment protection. Carbendazim is one of the extensive uses of pesticides in the agricultural industry. In this study, a simple method utilizing syringe filter has been applied as electrospray ionization emitter for mass spectrometric identification and quantification of carbendazim in complex matrices including soil, natural water, and fruit juice samples, which contain many insoluble materials. With online syringe filter of the complex samples, most of insoluble materials such as soil were excluded in spray ionization process due to the filter effect, and analytes were subsequently sprayed out from syringe needle for mass spectrometric detection. The pore sizes of filters and diameters of syringe needles also were investigated. The analytical performances, including the linear range (1–200 ng·mL−1), limit of detection (0.2–0.6 ng·mL−1, S/N > 3), limit of quantitation (3.5–8.6 ng·mL−1, S/N > 10), reproducibility (6.4%–12.5%, n = 6), and recoveries (72.1%–91.0%, n = 6) were well acceptable for direct analysis of raw samples. Matrix effect for detection of carbendazim in soil samples also was experimentally investigated. This study demonstrated that syringe filter needle coupled with electrospray ionization mass spectrometry is a simple, efficient, and sensitive method for detection of pesticide residues in water, soil, and fruit juice for risk assessment.
Electrophysiological characteristics of the frontal nerve in patients with herpetic ophthalmic neuralgia
Authors: XU Gang , Zhou Chaosheng , Liu Shasha , Li Wen , Tang Weizhen
Published: January 2018

Introduction: The aim of this study was to explore a method for obtaining sensory nerve action potentials (SNAPs) of the supratrochlear (STN) and supraorbital (SON) nerves and evaluate the function of affected nerves in patients with herpetic ophthalmic neuralgia (HON). Methods: Thirty healthy volunteers and 40 subjects with subacute HON participated in this study. Results: The amplitudes and sensory conduction velocities (SCVs) that predicted HON were identified. The corresponding cutoff values for the amplitudes ranged from 11.10 μV to 12.45 μV. The corresponding cutoff values for the SCVs ranged from 43.14 m/s to 44.64 m/s. SCVs were markedly lower on the affected side compared with healthy volunteers (P < 0.05), and the amplitudes of SNAPs on the affected side were decreased by 36% compared with healthy volunteers (P < 0.05). Discussion: SCVs of STN and SONs can be obtained with the 3‐channel method and used to evaluate myelinated fibers in patients with HON. Muscle Nerve 57: 973–980, 2018
cfDNA screening and diagnosis of monogenic disorders – where are we heading?
Authors: Chiu Eunice Ka Long , Hui Winnie Wai In , Chiu Rossa Wai Kwun
Published: January 2018

Cell‐free fetal DNA analysis for non‐invasive prenatal screening of fetal chromosomal aneuploidy has been widely adopted for clinical use. Fetal monogenic diseases have also been shown to be amenable to non‐invasive detection by maternal plasma DNA analysis. A number of recent technological developments in this area has increased the level of clinical interest, particularly as one approach does not require customized reagents per mutation. The mutational status of the fetus can be assessed by determining which parental haplotype that fetus has inherited based on the detection of haplotype‐associated SNP alleles in maternal plasma. Such relative haplotype dosage analysis requires the input of the parental haplotype information for interpretation of the fetal inheritance pattern from the maternal plasma DNA data. The parental haplotype information can be obtained by direct means, reducing the need to infer haplotypes using DNA from other family members. The technique also allows the assessment of complex mutations and has multiplexing capabilities where a number of genes and mutations can be assessed at the same time. These advantages allow non‐invasive prenatal diagnosis of fetal monogenic diseases to be much more scalable. These applications may drive the next wave of clinical adoption of cell‐free fetal DNA testing. © 2018 The Authors Prenatal Diagnosis Published by John Wiley & Sons Ltd
Effect of FAK inhibitor VS‐6063 (defactinib) on docetaxel efficacy in prostate cancer
Authors: Lin Hui‐Ming , Lee Brian Y. , Castillo Lesley , Spielman Calan , Grogan Judith , Yeung Nicole K. , Kench James G. , Stricker Phillip D. , Haynes Anne‐Maree , Centenera Margaret M. , Butler Lisa M. , Shreeve S. Martin , Horvath Lisa G. , Daly Roger J.
Published: January 2018

Background

Docetaxel, the standard chemotherapy for metastatic castration‐resistant prostate cancer (CRPC) also enhances the survival of patients with metastatic castration‐sensitive prostate cancer (CSPC) when combined with androgen‐deprivation therapy. Focal Adhesion Kinase (FAK) activation is a mediator of docetaxel resistance in prostate cancer cells. The aim of this study was to investigate the effect of the second generation FAK inhibitor VS‐6063 on docetaxel efficacy in pre‐clinical CRPC and CSPC models.

Methods

Docetaxel‐resistant CRPC cells, mice with PC3 xenografts, and ex vivo cultures of patient‐derived primary prostate tumors were treated with VS‐6063 and/or docetaxel, or vehicle control. Cell counting, immunoblotting, and immunohistochemistry techniques were used to evaluate the treatment effects.

Results

Docetaxel and VS‐6063 co‐treatment caused a greater decrease in the viability of docetaxel‐resistant CRPC cells, and a greater inhibition in PC3 xenograft growth compared to either monotherapy. FAK expression in human primary prostate cancer was positively associated with advanced tumor stage. Patient‐derived prostate tumor explants cultured with both docetaxel and VS‐6063 displayed a higher percentage of apoptosis in cancer cells, than monotherapy treatment.

Conclusions

Our findings suggest that co‐administration of the FAK inhibitor, VS‐6063, with docetaxel represents a potential therapeutic strategy to overcome docetaxel resistance in prostate cancer.
Fine structure in the hydrogen atom boxed in a spherical impenetrable cavity
Authors: Rojas R. A. , Aquino N. , Flores‐Riveros A.
Published: January 2018

The spectrum of the hydrogen atom confined in a spherical impenetrable box of radius Rc has been investigated by many authors up to date, but not at the level of relativistic corrections. It is well known that, as Rc diminishes, all energy levels and the pressure increase very rapidly, whereas the polarizability goes to zero. In this report, we have computed the relativistic corrections that underlie the fine structure of the confined hydrogen atom, as a function of Rc. Such corrections correspond to relativistic kinetic energy, spin‐orbit coupling and the Darwin term, which are calculated in the frame of time‐independent perturbation theory, for which, use was made of the exact confined hydrogen atom wave functions. We show that for a confinement radius of 0.5 au the relativistic corrections increase up to three orders of magnitude with respect to those corresponding to the free atom. As Rc decreases, the kinetic energy correction and the spin‐orbit coupling for
become negative whereas their absolute value and the Darwin term, which is positive, increase very rapidly.
Investigation of cadmium accumulation mechanism in hepatopancreas of Patinopecten yessoensis by synchrotron radiation X‐ray absorption fine structure and synchrotron radiation X‐ray fluorescence analyses
Authors: Terada Kenji , Abe Yoshinari , Nakai Izumi , Maruhashi Shingo , Miura Shigetoshi , Honda Kotaro , Tomooka Yasuhiro
Published: January 2018

Chemical state of cadmium in a hepatopancreas of a scallop (Patinopecten yessoensis) was studied by means of synchrotron radiation‐based X‐ray analytical techniques. X‐ray absorption fine structure (XAFS) and X‐ray fluorescence (XRF) imaging were used to identify the chemical state and the distribution of cadmium in the hepatopancreas, respectively. The results of in vivo Cd K‐edge XAFS suggested that the neighboring atoms of the cadmium in the hepatopancreas are of sulfur. Therefore, we propose that cadmium was accumulated by a metalloprotein with sulfur. Micro XRF imaging of thin sections of the hepatopancreas showed that cadmium is distributed on the surface of intestinal epithelia and concentrated in the internal tissue of the hepatopancreas. These results indicated that scallops accumulate cadmium inside the hepatopancreas through the intestinal epithelium.
Lecture on Methylmercury Poisoning in Minamata (MPM)
Authors: Yokoyama Hisashi
Published: January 2018

This chapter outlines the methylmercury poisoning in Minamata (MPM): about the history, symptom pathogenesis, research on the causal agent, and responses of the national and local governments and the responsible company, i.e., Chisso, to the outbreak of MPM. A book written by Nishimura and Okamoto (2001) played an important role to clarify the mechanism of the MPM outbreak. Based on this book and the published data on mercury concentrations of aquatic organisms and newborns’ umbilical cords, how methylmercury generated in the plant, flew into the sea, transferred to aquatic organisms, and was consumed by residents are explained. Victims of MPM, compensation and environmental restructure, and court ruling against this incident are described. Based on lecture notes from a university course, students’ suggestions for avoiding a repeat of the tragedy are also introduced.