bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted dianthin is a powerful toxin to treat pancreatic carcinoma when applied in combination with the glycosylated triterpeneSO1861
Authors: Bhargava Cheenu , Dürkop Horst , Zhao Xiangli , Weng Alexander , Melzig Matthias F. , Fuchs Hendrik
Published: July 2017

Targeted cancer therapy provides the basis for the arrest of tumor growth in aggressive pancreatic carcinoma; however, a number of protein‐based targeted toxins lack efficacy due to insufficient endosomal escape after being endocytosed. Therefore, we tested a fusion protein of the ribosome‐inactivating protein dianthin and human epidermal growth factor in combination with a glycosylated triterpene (SO1861) that serves as an endosomal escape enhancer.In vitroinvestigations with the pancreatic carcinoma cell lines BxPC‐3 andMIAPaCa‐2 revealed no significant differences to off‐target cells in the half maximal inhibitory concentration (IC50) for the fusion protein. In contrast, combination withSO1861 decreased theIC50for BxPC‐3 cells from 100 to 0.17 nm, whereas control cells remained unaffected. Monotherapy of BxPC‐3 xenografts inCD‐1 nude mice led to a 51.7% average reduction in tumor size (40.8 mm3) when compared to placebo; however, combined treatment withSO1861 resulted in a more than 13‐fold better efficacy (3.0 mm3average tumor size) with complete regression in 80% of cases. Immunohistochemical analyses showed that tumor cells with lower target receptor expression are, in contrast to the combination therapy, able to escape from the monotherapy, which finally results in tumor growth. At the effective concentration, we did not observe liver toxicity and saw no other side effects with the exception of a reversible skin hardening at theSO1861 injection site, alongside an increase in platelet counts, plateletcrit, and platelet distribution width. In conclusion, combining a targeted toxin withSO1861 is proven to be a very promising approach for pancreatic cancer treatment.
Uplift and denudation history of the Akaishi Range, a thrust block formed by arc‐arc collision in central Japan: Insights from low‐temperature thermochronometry and thermokinematic modeling
Authors: Sueoka S. , Ikeda Y. , Kano K. , Tsutsumi H. , Tagami T. , Kohn B. P. , Hasebe N. , Tamura A. , Arai S. , Shibata K.
Published: July 2017

Fission track (FT), (U‐Th)/He (He), and U‐Pb data were used to identify the denudation history of the Akaishi Range, central Japan. The northern Akaishi Range is bounded on the east by the Itoigawa‐Shizuoka Tectonic Line Fault Zone (ISTL‐FZ). The thermochronometric ages progressively decrease with the decreasing distance to the ISTL‐FZ. Thermokinematic calculations suggest that the age pattern observed can be explained by 5–7.5 mm/yr reverse slip on the ISTL‐FZ that dips 34–45° west and soles onto detachment at 20–22.5 km depth. By assuming the same geometry and slip rate of the fault, the bedrock uplift rates and denudation rates are estimated at ~4 mm/yr. Thus, the uplift and denudation style of the northern Akaishi Range is well explained as a simple tilted thrust block that has been exhumed along the listric ISTL‐FZ. On the other hand, considering both the difference in apatite FT age and the active fault distribution, the southern Akaishi Range might be different in uplift origin and timing, although the difference in apatite FT ages between them may be attributable to the chlorine content variation in apatite. The inferred total denudation is larger than several kilometers and likely exceeds 10 km since the beginning of the northern Akaishi Range uplift, suggesting that the low‐relief surfaces on the ridges and the relatively constant elevations of the summits reflect postuplift denudation rather than preexisting low‐relief landforms.
The impact of higher‐order ionospheric effects on estimated tropospheric parameters in Precise Point Positioning
Authors: Zus F. , Deng Z. , Wickert J.
Published: July 2017

The impact of higher‐order ionospheric effects on the estimated station coordinates and clocks in Global Navigation Satellite System (GNSS) Precise Point Positioning (PPP) is well documented in literature. Simulation studies reveal that higher‐order ionospheric effects have a significant impact on the estimated tropospheric parameters as well. In particular, the tropospheric north‐gradient component is most affected for low‐latitude and midlatitude stations around noon. In a practical example we select a few hundred stations randomly distributed over the globe, in March 2012 (medium solar activity), and apply/do not apply ionospheric corrections in PPP. We compare the two sets of tropospheric parameters (ionospheric corrections applied/not applied) and find an overall good agreement with the prediction from the simulation study. The comparison of the tropospheric parameters with the tropospheric parameters derived from the ERA‐Interim global atmospheric reanalysis shows that ionospheric corrections must be consistently applied in PPP and the orbit and clock generation. The inconsistent application results in an artificial station displacement which is accompanied by an artificial “tilting” of the troposphere. This finding is relevant in particular for those who consider advanced GNSS tropospheric products for meteorological studies.
Monitoring deep inspiration breath hold for left‐sided localized breast cancer radiotherapy with an in‐house developed laser distance meter system
Authors: Jensen Christer A. , Abramova Tatiana , Frengen Jomar , Lund Jo‐Åsmund
Published: July 2017

Deep inspiration breath hold (DIBH) in left‐sided breast cancer radiotherapy is a technique to reduce cardiac and pulmonary doses while maintaining target coverage. This study aims at evaluating an in‐house developed DIBH system. Free‐breathing (FB) and DIBH plans were generated for 22 left‐sided localized breast cancer patients who had radiation therapy (RT) after breast‐conserving surgery. All patients were treated utilizing an in‐house laser distance measuring system. 50 Gy was prescribed, and parameters of interest were target coverage, left anterior descending coronary artery, (LAD) and heart doses. Portal images were acquired and the reproducibility and stability of DIBH treatment were compared to FB. The comparing result shows there is a significant reduction in all LAD and heart dose statistics for DIBH compared to FB plans without compromising the target coverage. The maximum LAD dose was reduced from 43.7 Gy to 29.0 Gy and the volume of the heart receiving >25 Gy was reduced from 3.3% to 1.0% using the in‐house system, both statistically significant. The in‐house system gave a reproducible and stable DIBH treatment where the systematic error ∑, and random error σ, were less than 2.2 mm in all directions, but were not significantly better than at FB. The system was well tolerated and all patients completed their treatment sessions with DIBH.
Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes
Authors: van Coevorden‐Hameete Marleen H. , van Beuningen Sam F.B. , Perrenoud Matthieu , Will Lena M. , Hulsenboom Esther , Demonet Jean‐Francois , Sabater Lidia , Kros Johan M. , Verschuuren Jan J.G.M. , Titulaer Maarten J. , de Graaff Esther , Sillevis Smitt Peter A.E. , Hoogenraad Casper C.
Published: July 2017

Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti‐TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell‐based assay. Anti‐TRIM46 antibodies can occur in patients with diverse neurological syndromes and are associated with small‐cell lung carcinoma.
Gold‐Catalyzed [4+2]‐ and [3+3]‐Annulations of Ynamides with 1‐Yn‐3‐ols to Access Six‐Membered Carbocycles and Oxacycles via Three Distinct Cyclizations
Authors: Giri Sovan Sundar , Liu Rai‐Shung
Published: July 2017

Three distinct strategies for catalytic annulations between ynamides and 1‐yn‐3‐ols are described; the resulting carbo‐ and heterocycles were produced efficiently in one‐pot operations using a gold catalyst. The chemoselectivities of these annulations are controlled by variations of the substituents of the ynamides and the 1‐yn‐3‐ols. This reaction sequence involves initial alkoxylations of ynamides, followed by Claisen rearrangement of propargylic enol ethers, and ends with 6‐endo‐trig cyclizations of 1‐allenyl‐5‐amide intermediates. Among these cascade annulations, the cyclizations of 5‐allenyl‐1‐amides to yield 5,6‐dihydro‐2‐pyranones and 6‐alkylenecyclohex‐2‐ene‐1‐carboxamides are unprecedented in the literature.

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Chemical Origin of the Stability Difference between Copper(I)‐ and Silver(I)‐Based Halide Double Perovskites
Authors: Xiao Zewen , Du Ke‐Zhao , Meng Weiwei , Mitzi David B. , Yan Yanfa
Published: July 2017

Recently, CuI‐ and AgI‐based halide double perovskites have been proposed as promising candidates for overcoming the toxicity and instability issues inherent within the emerging Pb‐based halide perovskite absorbers. However, up to date, only AgI‐based halide double perovskites have been experimentally synthesized; there are no reports on successful synthesis of CuI‐based analogues. Here we show that, owing to the much higher energy level for the Cu 3d10 orbitals than for the Ag 4d10 orbitals, CuI atoms energetically favor 4‐fold coordination, forming [CuX4] tetrahedra (X=halogen), but not 6‐fold coordination as required for [CuX6] octahedra. In contrast, AgI atoms can have both 6‐ and 4‐fold coordinations. Our density functional theory calculations reveal that the synthesis of CuI halide double perovskites may instead lead to non‐perovskites containing [CuX4] tetrahedra, as confirmed by our material synthesis efforts.
Microfluidic Lithography of Bioinspired Helical Micromotors
Authors: Yu Yunru , Shang Luoran , Gao Wei , Zhao Ze , Wang Huan , Zhao Yuanjin
Published: July 2017

Considerable efforts have been devoted to developing artificial micro/nanomotors that can convert energy into movement. A flow lithography integrated microfluidic spinning and spiraling system is developed for the continuous generation of bioinspired helical micromotors. Because the generation processes could be precisely tuned by adjusting the flow rates and the illuminating frequency, the length, diameter, and pitch of the helical micromotors were highly controllable. Benefiting from the fast online gelation and polymerization, the resultant helical micromotors could be imparted with Janus, triplex, and core–shell cross‐sectional structures that have never been achieved by other methods. Owing to the spatially controlled encapsulation of functional nanoparticles in the microstructures, the helical micromotors can perform locomotion not only by magnetically actuated rotation or corkscrew motion but also through chemically powered catalytic reaction.
In Situ Localization of Enzyme Activity in Live Cells by a Molecular Probe Releasing a Precipitating Fluorochrome
Authors: Liu Hong‐Wen , Li Ke , Hu Xiao‐Xiao , Zhu Longmin , Rong Qiming , Liu Yongchao , Zhang Xiao‐Bing , Hasserodt Jens , Qu Feng‐Li , Tan Weihong
Published: July 2017

Current enzyme‐responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited‐state intramolecular proton transfer (ESIPT)‐based solid‐state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme‐responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion‐resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer.
Multicavity Metallosupramolecular Architectures
Authors: Vasdev Roan A. S. , Preston Dan , Crowley James D.
Published: July 2017

Discrete metallosupramolecular systems are often macrocyclic or cage‐like architectures with an accessible internal cavity. Guest molecules can reside within these cavities and much of the interest in these systems is derived from these fascinating host–guest interactions. A range of potential applications stem from the ability of these metallosupramolecular architectures to encapsulate guests. These applications include catalysis or acting as molecular reaction flasks, the molecular scavenging of pollutants, storage of reactive species, and drug delivery. Multicavity metallosupramolecular architectures combine the ability of large hollow assemblies to bind multiple guests concurrently with the binding specificity associated with small cages. A variety of different approaches to generating separate compartments within a single metallosupramolecular assembly have emerged. These include interpenetrated cages, cages with polytopic ligands that have a long backbone, and molecules that have two or more clefts. This review examines these approaches, and highlights key contributions to the field.
Hypospadias, Intrauterine Growth Restriction, and Abnormalities of the Placenta
Authors: Toufaily M. Hassan , Roberts Drucilla J. , Westgate Marie‐Noel , Hunt Anne‐Therese , Holmes Lewis B.
Published: July 2017

Background

Hypospadias is more common among male infants with growth restriction, defined as a birth weight less than the 10th centile, than in infants with a normal birth weight. Intrauterine growth retardation (IUGR) has been associated, also, with abnormalities of the placenta, such as maternal vascular malperfusion. In a consecutive sample of newborn infants, the association between hypospadias, IUGR and abnormalities of the placenta could be analyzed.

Methods

Affected infants were identified among 289,365 liveborn and stillborn infants in the Active Malformations Surveillance Program between 1972 and 2012. The four anatomic locations of the ectopic urethral opening, based on the recorded physical examination findings, were: (1) glandular; (2) subcoronal; (3) penile; (4) penoscrotal. Affected infants with associated malformations, a chromosome abnormality, teratogenic exposure, maternal diabetes mellitus, or multiple gestations were excluded.

Results

Three hundred sixteen affected infants were identified: 52.2% glandular, 11.7% subcoronal, 27.8% penile, and 8.2% penoscrotal. The highest frequency of IUGR (34.6%) was in the infants with the most severe hypospadias (penoscrotal). The 39 reports of placenta findings showed a high frequency of abnormalities.

Conclusion

An increased rate of occurrence of hypospadias and abnormalities of the placenta were present in infants with intrauterine growth restriction. The postulated cause of this association is a deficiency in the function of the placenta during weeks 10 to 14 of gestation when normal masculinization occurs due to an increase in the level of placental human chorionic gonadotropin and fetal testosterone. The cause of the placental deficiency has not been established. Birth Defects Research 110:122–127, 2018.© 2017 Wiley Periodicals, Inc.
Postnatal Evaluation of Cervical Ribs in Control Rats
Authors: Mukerji Pushkor , Glatt Christine , Gannon Shawn , Lewis Joseph M.
Published: July 2017

Background

Cervical ribs in rat fetuses have been widely reported to occur in controls as well as in response to various maternal chemical exposures. However, few evaluations of cervical ribs have been reported in rats postnatally. The available literature has indicated that the postnatal incidences of cervical ribs in control rats are no higher than in perinatal fetuses.

Methods

In a developmental toxicity study in rats conducted by the inhalation route, a control group of 44 time‐mated female rats was exposed to filtered air only from gestation day (GD) 6 to 20, and divided into two cohorts. For one cohort, fetuses were removed from dams by laparohysterectomy for skeletal evaluation on GD 21. The other cohort of dams was permitted to deliver, and adult offspring were euthanized on postnatal day 65 for a subsequent postnatal skeletal evaluation of cervical ribs.

Results

The incidence of cervical ribs (mean percentage of affected fetuses or adults per litter) was observed to increase during postnatal development, from 1.0% on GD 21 to 12.7% on postnatal day 65. Further evaluation is ongoing to determine whether these observations were attributable to the inhalation exposure conditions used in this study.

Conclusion

These results, while limited to the evaluation of one skeletal alteration in control rats, support the need for additional research into the area of postnatal development of skeletal abnormalities observed in developmental toxicity studies and the relevance of these skeletal observations to human risk assessment. Birth Defects Research 109:1301–1304, 2017. © 2017 Wiley Periodicals, Inc.
An Efficient Transformation Method for the Bioplastic‐Producing “Knallgas” Bacterium Ralstonia eutropha H16
Authors: Tee Kang Lan , Grinham James , Othusitse Arona M. , González‐Villanueva Miriam , Johnson Abayomi O. , Wong Tuck Seng
Published: July 2017

Ralstonia eutropha H16 (also known as Cupriavidus necator H16) is a Gram‐negative lithoautotrophic β‐proteobacterium with increasing biotechnological applications, including carbon capture and utilization, biopolymer synthesis, and biofuel production. Engineering of this organism is supported by the availability of its genome sequence and suitable plasmid systems. However, the lack of a simple and robust transformation method remains a challenge as it limits both the pace and ease of engineering this organism. To overcome this limitation, a systematic study is performed to evaluate the effects of different parameters on the transformation efficiency of R. eutropha H16. The optimized electroporation protocol uses R. eutropha H16 cells grown to OD600 0.6. These cells are made competent by a 15‐min incubation in 50 mM CaCl2, followed by two cell washes and final resuspension in 0.2 M sucrose prior to electroporation using 2.3 kV. This protocol achieves a transformation efficiency of (3.86 ± 0.29) × 105 cfu µg−1 DNA, a 103‐fold improvement compared to a previously published value for the same plasmid. This transformation method is a valuable tool for R. eutropha H16 research and will further enable the development of other advanced molecular biology methods for this industrially relevant microorganism.
Promoter Choice Impacts the Efficiency of Plant Glyco‐Engineering
Authors: Kallolimath Somanath , Gruber Clemens , Steinkellner Herta , Castilho Alexandra
Published: July 2017

Glyco‐modulation of therapeutic proteins produced in plants has shown great success. Plant‐based expression platforms for tailored human‐like N‐glycosylation are based on the overexpression of foreign genes. However, drawbacks such as protein miss targeting, interference with endogenous glycosyltransferases, or with plant development hamper the widespread use of the technology. Here a technique that facilitates the generation of recombinant proteins with targeted N‐glycosylation at high homogeneity is described. It is focused on the synthesis of human‐type β1,4‐galactosylation by the overexpression of the human β1,4‐galactosyltransferase (GalT) in Nicotiana benthamiana. A GalT construct that targets the enzyme to the required late Golgi compartment (STGalT) is transiently co‐expressed with two pharmaceutically relevant glycoproteins. The impact of eight promoters driving the expression of STGalT is evaluated by mass spectrometry (MS) ‐based analyses. It is shown that five promoters (amongst them high expressors) induce aberrant non‐human glycosylation. In contrast, three promoters, considered as moderately active, regulate gene expression to levels leading to an improved efficiency of di‐galactosylation (and subsequent sialylation) on the reporter proteins. The results point to the importance of promoter choice for optimizing glycan engineering processes.
Controlling localization of Escherichia coli populations using a two‐part synthetic motility circuit: An accelerator and brake
Authors: McKay Ryan , Hauk Pricila , Wu Hsuan‐Chen , Pottash Alex Eli , Shang Wu , Terrell Jessica , Payne Gregory F. , Bentley William E.
Published: July 2017

Probiotics, whether taken as capsules or consumed in foods, have been regarded as safe for human use by regulatory agencies. Being living cells, they serve as “tunable” factories for the synthesis of a vast array of beneficial molecules. The idea of reprogramming probiotics to act as controllable factories, producing potential therapeutic molecules under user‐specified conditions, represents a new and powerful concept in drug synthesis and delivery. Probiotics that serve as drug delivery vehicles pose several challenges, one being targeting (as seen with nanoparticle approaches). Here, we employ synthetic biology to control swimming directionality in a process referred to as “pseudotaxis.” Escherichia coli, absent the motility regulator cheZ, swim sporadically, missing the traditional “run” in the run:tumble swimming paradigm. Upon introduction of cheZ in trans and its signal‐generated upregulation, engineered bacteria can be “programmed” to swim toward the source of the chemical cue. Here, engineered cells that encounter sufficient levels of the small signal molecule pyocyanin, produce an engineered CheZ and swim with programmed directionality. By incorporating a degradation tag at the C‐terminus of CheZ, the cells stop running when they exit spaces containing pyocyanin. That is, the engineered CheZ modified with a C‐terminal extension derived from the putative DNA‐binding transcriptional regulator YbaQ (RREERAAKKVA) is consumed by the ClpXP protease machine at a rate sufficient to “brake” the cells when pyocyanin levels are too low. Through this process, we demonstrate that over time, these engineered E. coli accumulate in pyocyanin‐rich locales. We suggest that such approaches may find utility in engineering probiotics so that their beneficial functions can be focused in areas of principal benefit.
NMR investigation of water diffusion in different biofilm structures
Authors: Herrling Maria P. , Weisbrodt Jessica , Kirkland Catherine M. , Williamson Nathan H. , Lackner Susanne , Codd Sarah L. , Seymour Joseph D. , Guthausen Gisela , Horn Harald
Published: July 2017

Mass transfer in biofilms is determined by diffusion. Different mostly invasive approaches have been used to measure diffusion coefficients in biofilms, however, data on heterogeneous biomass under realistic conditions is still missing. To non‐invasively elucidate fluid–structure interactions in complex multispecies biofilms pulsed field gradient‐nuclear magnetic resonance (PFG‐NMR) was applied to measure the water diffusion in five different types of biomass aggregates: one type of sludge flocs, two types of biofilm, and two types of granules. Data analysis is an important issue when measuring heterogeneous systems and is shown to significantly influence the interpretation and understanding of water diffusion. With respect to numerical reproducibility and physico‐chemical interpretation, different data processing methods were explored: (bi)‐exponential data analysis and theΓdistribution model. Furthermore, the diffusion coefficient distribution in relation to relaxation was studied byD‐T2maps obtained by 2D inverse Laplace transform (2D ILT). The results show that the effective diffusion coefficients for all biofilm samples ranged from 0.36 to 0.96 relative to that of water. NMR diffusion was linked to biofilm structure (e.g., biomass density, organic and inorganic matter) as observed by magnetic resonance imaging and to traditional biofilm parameters: diffusion was most restricted in granules with compact structures, and fast diffusion was found in heterotrophic biofilms with fluffy structures. The effective diffusion coefficients in the biomass were found to be broadly distributed because of internal biomass heterogeneities, such as gas bubbles, precipitates, and locally changing biofilm densities. Thus, estimations based on biofilm bulk properties in multispecies systems can be overestimated and mean diffusion coefficients might not be sufficiently informative to describe mass transport in biofilms and the near bulk.
Bidirectional reporter assay using HAL promoter and TOPFLASH improves specificity in high‐throughput screening of Wnt inhibitors
Authors: Yamaguchi Kiyoshi , Zhu Chi , Ohsugi Tomoyuki , Yamaguchi Yuko , Ikenoue Tsuneo , Furukawa Yoichi
Published: July 2017

Constitutive activation of Wnt signaling plays an important role in colorectal and liver tumorigenesis. Cell‐based assays using synthetic TCF/LEF (T‐cell factor/lymphoid enhancer factor) reporters, as readouts of β‐catenin/TCF‐dependent transcriptional activity, have contributed greatly to the discovery of small molecules that modulate Wnt signaling. In the present study, we report a novel screening method, called a bidirectional dual reporter assay. Integrated transcriptome analysis identified a histidine ammonia‐lyase gene (HAL) that was negatively regulated by β‐catenin/TCF‐dependent transcriptional activity. We leveraged a promoter region of the HAL gene as another transcriptional readout of Wnt signaling. Cells stably expressing both an optimized HAL reporter and the TCF/LEF reporter enabled bidirectional reporter activities in response to Wnt signaling. Increased HAL reporter activity and decreased TCF/LEF reporter activity were observed simultaneously in the cells when β‐catenin/TCF7L2 was inhibited. Notably, this method could decrease the number of false positives observed when screening an inhibitor library compared with the conventional TCF/LEF assay. We found that Brefeldin A, a disruptor of the Golgi apparatus, inhibited the Wnt/β‐catenin signaling pathway. The utility of our system could be expanded to examine other disease‐associated pathways beyond the Wnt/β‐catenin signaling pathway.
Quantification of free fatty acids in human stratum corneum using tandem mass spectrometry and surrogate analyte approach
Authors: Dapic Irena , Kobetic Renata , Brkljacic Lidija , Kezic Sanja , Jakasa Ivone
Published: July 2017

The free fatty acids (FFAs) are one of the major components of the lipids in the stratum corneum (SC), the uppermost layer of the skin. Relative composition of FFAs has been proposed as a biomarker of the skin barrier status in patients with atopic dermatitis (AD). Here, we developed an LC‐ESI‐MS/MS method for simultaneous quantification of a range of FFAs with long and very long chain length in the SC collected by adhesive tape (D‐Squame). The method, based on derivatization with 2‐bromo‐1‐methylpyridinium iodide and 3‐carbinol‐1‐methylpyridinium iodide, allowed highly sensitive detection and quantification of FFAs using multiple reaction monitoring. For the quantification, we applied a surrogate analyte approach and internal standardization using isotope labeled derivatives of FFAs. Adhesive tapes showed the presence of several FFAs, which are also present in the SC, a problem encountered in previous studies. Therefore, the levels of FFAs in the SC were corrected using C12:0, which was present on the adhesive tape, but not detected in the SC. The method was applied to SC samples from patients with atopic dermatitis and healthy subjects. Quantification using multiple reaction monitoring allowed sufficient sensitivity to analyze FFAs of chain lengths C16–C28 in the SC collected on only one tape strip.
Multicomponent determination of traditional Chinese medicine preparation yin‐zhi‐huang injection by LC–MS/MS for screening of its potential bioactive candidates using HepaRG cells
Authors: Rao Zhi , Zhang Fan , Zhang Xiao‐Yi , Zhang Guo‐Qiang , Ma Yan‐Rong , Zhou Yan , Qin Hong‐Yan , Wu Xin‐An , Wei Yu‐Hui
Published: July 2017

Yin‐zhi‐huang (YZH) injection is an injectable multiherbal prescription derived from the ancient Chinese medicine formula of Yin‐chen‐hao‐tang, which is widely used in the clinic for the treatment of jaundice and chronic liver diseases. To date, the systematic study of the components in this multiherbal prescription still lacks suitable analytical methods that are able to simultaneously detect a broad array of components at low concentrations. In this study, a new liquid chromatography–tandem mass spectrometry method using dynamic multiple reaction monitoring mode was developed to determine multiple peaks in traditional Chinese medicine preparation YZH injection. This simple, selective and sensitive method enabled the quantification of 22 components with standard materials with a lower limit of quantification of 1.46–12.5 ng/mL in cell lysates. This method was successfully applied to celluar uptake and binding investigation of components in YZH injection. The results indicated that this strategy might be a useful approach for rapidly screening of the potential bioactive candidates from YZH injection, and the discovered candidates could be used to investigate the pharmacodynamics in further studies.
Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs)
Authors: Sen Utsav , Shenoy P Sudheer , Bose Bipasha
Published: July 2017

Colorectal cancer is one of the global causes of cancer deaths. Cancer stem cells (CSCs) inside the tumour niche responsible for metastasis and relapses, and hence need to be targeted for cancer therapeutics. Although dietary fibre and lifestyle changes have been recommended as measures for colorectal cancer prevention, no such recommendations are available for using water soluble vitamins as prophylaxis measure for colorectal cancers. High dose of Vitamin C has been proven to selectively kill colon cancer cells having BRAF and KRAS mutations by inducing oxidative stress. In this study, we show for the first time the opposing effects of the low and high dose of Vitamin C and vitamin B3 on colon CSCs isolated from HT‐29 and HCT‐15 colorectal carcinoma cell lines. At small doses, both of these vitamins exerted a cell proliferative effect only on CSCs, while there was no change in the proliferation status of non‐stem cancer cells and wild‐type (WT) populations. On the other hand, the death effects induced by high doses of Vitamin C and B3 were of the order of 50–60% and ∼30% on CSCs from HT‐29 and HCT15, respectively. Interestingly, the control fibroblast cell line (NIH3T3) was highly refractory all the tested concentrations of Vitamin C and B3, except for the highest dose – 10,000 μg of Vitamin C that induced only 15% of cell death. Hence, these results indicate the future scope of use of therapeutic doses of Vitamin C and B3 especially in patients with advanced colorectal cancer.
Induction treatment of acute myeloid leukemia in an elderly patient with intramarrow injection/administration of cytarabine. Second case report
Authors: Islam Anwarul
Published: July 2017

Key Clinical Message

We show for the second time that intramarrow injection/administration of chemotherapeutic agents such as cytarabine (Ara‐C) can be used safely and effectively and is associated with no toxicity, promising antileukemic activity and possible improved survival.
Reactivity of the Sterically Demanding Siloxanediol Mes2Si(OH)(μ‐O)Si(OH)Mes2 Towards Water and Ether Molecules
Authors: Roesch Philipp , Warzok Ulrike , Enke Martin , Müller Robert , Schattenberg Caspar , Schalley Christoph A. , Kaupp Martin , Braun Thomas , Wittwer Philipp
Published: July 2017

A series of isotopologues of the siloxanediol Mes2Si(OH)(μ‐O)Si(OH)Mes2 (3 a) (Mes=2,4,6‐trimethylphenyl) were synthesized by reactions of the corresponding disiloxane precursors Mes2Si(μ‐O)2SiMes2 (2 a), Mes2Si(μ‐17O)2SiMes2 (2 b) or Mes2Si(μ‐18O)2SiMes2 (2 c) with an excess of H2O, H217O or H218O. NMR and IR signal assignments for the siloxanediols in benzene are supported by quantum‐chemical calculations, which indicate small energy differences between trans and cis conformers, the latter of which exhibits an intramolecular hydrogen bond. 1H NMR as well as IR data suggest the presence of a mixture of both conformers in C6D6. Hydrogen‐bonded adducts of Mes2Si(OH)(μ‐O)Si(OH)Mes2 with ethers such as diethylether, dimethoxyethane or dioxane were observed in the solid state, where they form polymeric chain‐like structures. The latter appear to be stable only in the crystal. 17O{1H} NMR and IR data in THF solution suggest an interaction of 3 a with at least one THF molecule, whereas diethylether appears not to interact. Water adducts form neither in solution nor in the solid state as indicated by NMR and ATR IR data. 17O{1H} NMR and ESI‐MS experiments illustrate the remarkably high stability of the siloxanediols towards water and show no evidence for intra‐ or intermolecular oxygen‐exchange reactions. In marked contrast, a stepwise exchange of all three oxygen atoms‐including the one in the Si‐O‐Si bridge‐occurred in the gas phase, when [Mes2Si(18OH)(μ‐18O)Si(18O)Mes2]− was treated with H2O in the hexapole of an ESI FT‐ICR mass spectrometer. The scrambling between the bridging and the other oxygen atoms likely proceeds through cyclic Si2O2 intermediates.
Investigation of wax deposit ‘sloughing’ from paraffinic mixtures in pipe flow
Authors: Sinha Chandni , Mehrotra Anil K.
Published: July 2017

Deposit ‘sloughing’ from ‘waxy’ crude oils has been described in the literature as a possible mechanism, leading to partial or complete dislodging of the deposit from the pipe wall due to changes in flow parameters. A bench‐scale flow loop apparatus was used to investigate ‘sloughing’ with prepared single‐phase ‘waxy’ mixtures of a multicomponent paraffinic wax dissolved in a multicomponent solvent. Experiments were performed to study the changes in the deposit‐layer thickness due to step increments in the ‘waxy’ mixture flow rate, the mixture temperature, and the coolant temperature. It was observed that the deposit‐layer thickness decreased with an increase in each of the three parameters; however, a complete or sudden dislodging of the deposit‐layer did not occur in any of the experiments. A steady‐state heat‐transfer model was used to predict the variation in the deposit mass or thickness due to changes in the selected parameters. In each case, the step‐wise decrease in the deposit thickness, as observed experimentally, was predicted to be caused by changes in the thermal resistance and/or thermal driving force.
PIV investigation of the flow features of double and single 45° up‐pumping pitched blade turbines in a square tank
Authors: Wang Cunteng , Xu Ying , Wu Yuebin , An Zicheng
Published: July 2017

The non‐conventionally square stirred tank with up‐pumping impellers has been recently adopted in wastewater treatment processes due to its simplicity and high efficiency. In this paper, the time‐averaged flow fields in the square tank with both double and single 45° up‐pumping pitched blade turbines (PBTs) are investigated using particle image velocimetry (PIV). Flow field generated by double impellers are directly compared with the flow fields by single impeller. The flow number (FI), anisotropy, total kinetic energy, and energy dissipation rate are calculated to further investigate the flow features of the double impellers and single impeller. The results show that the high velocity region generated by a single impeller is about 0.4T (T is the length of square cross‐section of tank) in z direction. Flow number of the upper impeller is much larger than that of the lower impeller. In flow fields with a single impeller, the higher the impeller, the larger the flow number. The high flow anisotropy in terms of large scales occurs in the areas both above and beneath the impeller and near wall region. However, the high kinetic energy area corresponds to the high velocity region. Three numerical methods commonly used in the traditional cylindrical tank are employed to calculate . The maximum happens in areas near the impeller. Three methods give similar dissipation rate distributions but different values, which is the same as that in the cylindrical tank. It means that these methods could also be well used in square stirred tanks.
Experimental validation of equilibrium based mathematical modelling of liquid‐liquid phase transfer catalysis
Authors: Vir Anil B. , Pushpavanam Subramaniam
Published: July 2017

The reaction between two compounds which reside in immiscible phases can be accelerated using a phase transfer catalyst. The catalyst helps to transfer a species ion from one phase to the other phase, thus promoting its reaction. Several mechanisms have been proposed to describe phase transfer catalyzed reactions. In this work, we have carried out an experimental and theoretical study of phase transfer catalysis in batch mode. A mathematical model is developed which helps to predict the progress of the reaction under different operating conditions. Here the different species in the aqueous phase are assumed to be in equilibrium and these react with the species in the organic phase. The effect of diffusional resistance inside the dispersed organic phase is shown to be negligible. The two reaction systems studied are the phase transfer catalyzed (i) thioetherification and (ii) benzyl alcohol oxidation using sodium hypochlorite. Batch experiments were performed to determine the effect of catalyst loading, solvent dilution, and pH. The experimental results show that with an increase in catalyst loading, the phase transfer catalyzed reactions were accelerated. The use of a minimal amount of solvent results in a better performance. Benzyl alcohol oxidation is favoured under low pH conditions. The developed model is able to capture the performance of the system over a wide range of operating conditions accurately.
Kinetics of simultaneous HDS of DBT and 4‐MDBT/4,6‐DMDBT over CoMoP/γ‐Al2O3catalysts
Authors: Ali Syed A. , Bdwi Emad A. S. , Hossain Mohammad M.
Published: July 2017

A series of CoMo/γ‐Al2O3 catalysts were prepared with an addition of 0.0, 0.5, 1.0, or 1.5 % phosphorus pentaoxide to investigate the influence of phosphorus addition on the simultaneous hydrodesulphurization (HDS) of refractory sulphur compounds. Two sets of HDS experiments were carried out using sulphur bearing model compounds: (i) DBT (dibenzothiophene) with 4‐MDBT (4‐methyl dibenzothiophene) and (ii) DBT (dibenzothiophene) with 4,6‐DMDBT (4,6‐dimethyl dibenzothiophene). The Langmuir‐Hinshelwood mechanism based kinetics model was developed from the experimental conversion and product distribution data for simultaneous HDS of the two sulphur compounds via direct desulphurization (DDS) and hydrogenation (HYD) routes. The kinetic model fits the experimental data quite adequately for all the species. The HDS rate for DBT was found to be approximately 2 and 7 times higher than that estimated for 4‐MDBT and 4,6‐DMDBT, respectively. Enhancement of HDS rate by P addition was observed up to 0.01 g/g (1.0 wt%) P2O5 while a higher amount of P is not advantageous. A marginal preference towards HYD pathway was observed for the HDS of 4,6‐DMDBT while the DDS route was predominant during the HDS of DBT and 4‐MDBT.The trends in values of the rate constants estimated by the Langmuir‐Hinshelwood kinetic model compared well with pseudo‐first rate constants.
Spatial and Temporal Variation of Parameters in Wadi Andlou, Tunisia‐Pollution by Pulp Mill Discharge
Authors: Ltifi Abdelkader , Saidi Neila , Rabhi Mokded , Sealey Kathleen S. , Hafiane Amor , Smaoui Abderrazak , Abdelly Chedly
Published: July 2017

This study evaluated space‐time variation of water quality data sets for the Wadi Andlou Kasserine, Tunisia, using multivariate analytical techniques including cluster analysis, principal component analysis (PCA) and correlation analysis (CA). The present study showed that values of temperature (T), electrical conductivity (EC), biochemical oxygen demand (BOD), chemical oxygen demand (COD), chloride, phosphate, sulfate, fecal coliform, Streptococcus, Salmonella spp., and Enterococci were significantly higher in the dry season compared to samples taken in the wet season. Concurrently, pH, dissolved oxygen (DO), turbidity, suspended matter (SM), presented values significantly lower in dry season than surveys in rainy season. The following parameters BOD5, COD, , Cl−, SM, Salmonella spp. did not meet the Tunisian standard NT 106 for surface water quality. Analysis of pollutant concentrations via PCA showed that the two first components accounted for 87.34 and 93.17% of the total variance for dry and rainy season sampling, respectively. The first component included T, pH, EC, SM, , Cl−, , turbidity, COD, BOD, , Enterococci, fecal coliform and streptococcus, Salmonella spp., and total bacteria. The second included DO and . Cluster analysis identified the five sampling sites into three groups in the rainy and dry season based on seasonal differences and various pollution levels caused by physicochemical and bacteriological properties. The results suggest that future monitoring can include fewer sampling sites, and stratified random sampling plans can save time and resources.
Phase contrast cell detection using multilevel classification
Authors: Essa Ehab , Xie Xianghua
Published: July 2017

In this paper, we propose a fully automated learning‐based approach for detecting cells in time‐lapse phase contrast images. The proposed system combines 2 machine learning approaches to achieve bottom‐up image segmentation. We apply pixel‐wise classification using random forests (RF) classifiers to determine the potential location of the cells. Each pixel is classified into 4 categories (cell, mitotic cell, halo effect, and background noise). Various image features are extracted at different scales to train the RF classifier. The resulting probability map is partitioned using the k‐means algorithm to form potential cell regions. These regions are expanded into the neighboring areas to recover some missing or broken cell regions. To validate the cell regions, another machine learning method based on the bag‐of‐features and spatial pyramid encoding is proposed. The result of the second classifier can be a validated cell, a merged cell, or a noncell. In the case that the cell region is classified as a merged cell, it is split by using the seeded watershed method. The proposed method is demonstrated on several phase contrast image datasets, ie, U2OS, HeLa, and NIH 3T3. In comparison to state‐of‐the‐art cell detection techniques, the proposed method shows improved performance, particularly in dealing with noise interference and drastic shape variations.
Self‐Assembled DNA Nanostructures for Biomedical Applications
Authors: Song Linlin , Jiang Qiao , Wang Zhen‐Gang , Ding Baoquan
Published: July 2017

DNA has been demonstrated to be a promising engineering material for the fabrication of pre‐designed nanostructures and nanodevices, which feature structural programmability, spatial addressability, dynamic mechanics, and biocompatibility. Here, we review the recent progress in the design, construction and biomedical applications of DNA nanostructures, particularly imaging probes and drug delivery carriers. We discuss several key points for in vivo biomedical applications of DNA‐based delivery systems, such as the cost and safety issues. In the end, we explore the challenges and opportunities of DNA nanotechnology in the field of nanomedicine.
Application of Liquid Biopsies in Cancer Targeted Therapy
Authors: Sumanasuriya S , Lambros MB , de Bono JS
Published: July 2017

As a growing body of evidence demonstrates intertumoral and intratumoral heterogeneity and clonal evolution, both during carcinogenesis and also throughout treatment resulting in acquired drug resistance, the utility of blood‐based assays or “liquid biopsies” is becoming increasingly recognized in clinical practice and trial design. “Liquid biopsies” provide a less invasive approach to the current gold standard of interrogating tumors by tissue biopsies, which are frequently unfeasible, associated with morbidity, and cannot be performed as often.
The Introduction and Clinical Use of Cardiac‐Specific Troponin Assays
Authors: Antman Elliott M.
Published: July 2017

The earliest biomarkers introduced to diagnose myocardial infarction (MI) such as aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) lacked cardiac specificity and were replaced by creatine kinase (CK), the CK‐MB isoenzyme, and ultimately the cardiac‐specific troponins (cTnT and cTnI). This has opened up the possibilities of ruling out MI more rapidly and also identifying patients with a chronic elevation of cTn and a poor prognosis in a range of cardiac conditions.
Employee‐Driven Sustainability Performance Assessment in Public Organisations
Authors: Coutinho Vera , Domingues Ana Rita , Caeiro Sandra , Painho Marco , Antunes Paula , Santos Rui , Videira Nuno , Walker Richard M. , Huisingh Donald , Ramos Tomás B.
Published: July 2017

Organisations are increasingly adopting sustainability performance assessment tools. However, these formal organisational sustainability assessments are typically managed and prepared by technical staff. There is a lack of research on approaches that enable a stakeholder‐driven performance assessment. This paper develops a framework of informal/complementary stakeholder‐driven sustainability performance assessment, from the perspective of employee voluntary collaboration. The framework composes a checklist of questions covering the main sustainability domains: perceptions, individual practices, and voluntary monitoring indicators. In an exploratory case study in a public organisation, the checklist was evaluated by employees in a participatory workshop. The evaluation criteria of understanding and usefulness were rated more positively than reliability. This paper shows a novel way of integrating employee inputs for informal sustainability assessment and supports the importance of empowering public organisations, thereby increasing their understanding of sustainability management frameworks. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Cytological features of the Warthin‐like variant of salivary mucoepidermoid carcinoma
Authors: Hang Jen‐Fan , Shum Chung H. , Ali Syed Z. , Bishop Justin A.
Published: July 2017

Warthin‐like mucoepidermoid carcinoma is a recently proposed variant of musoepidermoid carcinoma. Histologically, it is characterized by its close resemblance to Warthin tumor, including dense lymphocytic infiltration, flattened intermediate epithelium resembling squamous metaplasia, and cystic change. Given its histologic similarity to Warthin tumor, confirmatory testing for MAML2 rearrangement is often required for this diagnosis. Here we present the first cytologic reports of two 53‐year‐old female patients with parotid masses. In both cases, the fine needle aspirations showed fragments of bland epithelium with a squamous appearance, mucinous cyst content, and focal lymphocytic background. Neither frank keratinization nor mucinous cells were identified in the smears. Fluorescence in situ hybridization (FISH) study confirmed MAML2 rearrangement on the resection specimens in both. Other cytologic differential diagnoses, including Warthin tumor with metaplasia, lymphadenoma, and lymphoepithelial cyst, were briefly discussed.