bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous Consecutive Reactions with Inter‐Reaction Solvent Exchange by Membrane Separation
Authors: Peeva Ludmila , Da Silva Burgal Joao , Heckenast Zsofia , Brazy Florine , Cazenave Florian , Livingston Andrew
Published: September 2016

Pharmaceutical production typically involves multiple reaction steps with separations between successive reactions. Two processes which complicate the transition from batch to continuous operation in multistep synthesis are solvent exchange (especially high‐boiling‐ to low‐boiling‐point solvent), and catalyst separation. Demonstrated here is membrane separation as an enabling platform for undertaking these processes during continuous operation. Two consecutive reactions are performed in different solvents, with catalyst separation and inter‐reaction solvent exchange achieved by continuous flow membrane units. A Heck coupling reaction is performed in N,N‐dimethylformamide (DMF) in a continuous membrane reactor which retains the catalyst. The Heck reaction product undergoes solvent exchange in a counter‐current membrane system where DMF is continuously replaced by ethanol. After exchange the product dissolved in ethanol passes through a column packed with an iron catalyst, and undergoes reduction (>99 % yield).
1H‐Detected Solid‐State NMR Studies of Water‐Inaccessible Proteins In Vitro and In Situ
Authors: Medeiros‐Silva João , Mance Deni , Daniëls Mark , Jekhmane Shehrazade , Houben Klaartje , Baldus Marc , Weingarth Markus
Published: September 2016

1H detection can significantly improve solid‐state NMR spectral sensitivity and thereby allows studying more complex proteins. However, the common prerequisite for 1H detection is the introduction of exchangeable protons in otherwise deuterated proteins, which has thus far significantly hampered studies of partly water‐inaccessible proteins, such as membrane proteins. Herein, we present an approach that enables high‐resolution 1H‐detected solid‐state NMR (ssNMR) studies of water‐inaccessible proteins, and that even works in highly complex environments such as cellular surfaces. In particular, the method was applied to study the K+ channel KcsA in liposomes and in situ in native bacterial cell membranes. We used our data for a dynamic analysis, and we show that the selectivity filter, which is responsible for ion conduction and highly conserved in K+ channels, undergoes pronounced molecular motion. We expect this approach to open new avenues for biomolecular ssNMR.
Supertetrahedral Networks and Lithium‐Ion Mobility in Li2SiP2 and LiSi2P3
Authors: Haffner Arthur , Bräuniger Thomas , Johrendt Dirk
Published: September 2016

The new phosphidosilicates Li2SiP2 and LiSi2P3 were synthesized by heating the elements at 1123 K and characterized by single‐crystal X‐ray diffraction. Li2SiP2 (I41/acd, Z=32, a=12.111(1) Å, c=18.658(2) Å) contains two interpenetrating diamond‐like tetrahedral networks consisting of corner‐sharing T2 supertetrahedra [(SiP4/2)4]. Sphalerite‐like interpenetrating networks of uniquely bridged T4 and T5 supertetrahedra make up the complex structure of LiSi2P3 (I41/a, Z=100, a=18.4757(3) Å, c=35.0982(6) Å). The lithium ions are located in the open spaces between the supertetrahedra and coordinated by four to six phosphorus atoms. Temperature‐dependent 7Li solid‐state MAS NMR spectroscopic data indicate high mobility of the Li+ ions with low activation energies of 0.10 eV in Li2SiP2 and 0.07 eV in LiSi2P3.
How to use QSPR‐type approaches to predict properties in the context of Green Chemistry
Authors: Fayet Guillaume , Rotureau Patricia
Published: September 2016

Green Chemistry is an active field of chemical research in which the ultimate targets are to promote high‐value, safe, clean products from renewable resources using inherently safer and clean processes. Until recently, the main efforts focused on the production of chemicals based on renewable resources by cleaner processes, notably by eliminating or substituting solvents.

Quantitative Structure‐Property Relationships (QSPR) offer the opportunity to also take into account safety issues (in particular fire and explosion risks) in the early steps of development of chemicals and processes in the context of Green Chemistry. Based on robust methods for their development and validation, these predictive approaches allow access to the properties of substances based only on the knowledge of their molecular structures, even before their synthesis. QSPR models have been developed for various kinds of properties, including physico‐chemical hazards, for diverse families of compounds.

They can be used as virtual screening tools to identify the best candidate among a series of possible compounds (within databases of products) for a target application and even in computer‐aided molecular design to propose alternative molecular structures, for instance for substitution purposes. So they represent very relevant tools to take into account the physico‐chemical hazards of substances together with targeted functional properties from the early stages of R&D projects toward safe‐by‐design “green” products and processes. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
Camelid VHH affinity ligands enable separation of closely related biopharmaceuticals
Authors: Pabst Timothy M. , Wendeler Michaela , Wang Xiangyang , Bezemer Sandra , Hermans Pim , Hunter Alan K.
Published: September 2016

Interest in new and diverse classes of molecules such as recombinant toxins, enzymes, and blood factors continues to grow for use a biotherapeutics. Compared to monoclonal antibodies, these novel drugs typically lack a commercially available affinity chromatography option, which leads to greater process complexity, longer development timelines, and poor platformability. To date, for both monoclonal antibodies and novel molecules, affinity chromatography has been mostly reserved for separation of process‐related impurities such as host cell proteins and DNA. Reports of affinity purification of closely related product variants and modified forms are much rarer. In this work we describe custom affinity chromatography development using camelid VHH antibody fragments as "tunable" immunoaffinity ligands for separation of product‐related impurities. One example demonstrates high selectivity for a recombinant immunotoxin where no binding was observed for an undesired deamidated species. Also discussed is affinity purification of a coagulation factor through specific recognition of the gamma‐carboxylglutamic acid domain.
Surface Functionalization by Bioactive Coating on Magnetic Nanoparticles for Bio‐sensing Application
Authors: Jeong Jong‐Chan , Jang Yoon‐Hee , Yang Sung Yun
Published: September 2016

Magnetic nanoparticles (MNPs) have been drawing much technological interests in medical diagnostics and therapy. However, it remains a challenge reducing false signal arising from non‐specific interactions. Here, we coated MNPs with polyelectrolyte multilayer (PEM) films by layer‐by‐layer deposition with poly(allylamine hydrochloride) and poly(acrylic acid). The polyelectrolytes multilayers film prevented irreversible coagulation of MNPs and could be used for conjugation of biomolecules on the MNPs. Furthermore, we also demonstrated a potential application of the PEM‐coated MNPS into a microfluidic system.
Exact Fundamental Function for the One‐Dimensional Random Walk with a Perfect Mirror under the External Field
Authors: Yoon Joung‐Hahn , Kim Hyojoon
Published: September 2016

The exact analytical probability function is presented for the random walk with a perfect mirror under the constant external field in one dimension. Unlike the field‐free solution, the symmetry around the boundary is broken by the external field and the fundamental function is not given by a simple form. We prove the solution by mathematical induction method and numerical simulations. Monte Carlo simulations can be replaced by the function without statistical noise. Based on this function, we also obtain the solution for the continuum diffusion‐influenced reaction, which is shown to be superior to the known solution especially for the system with a strong external field.
Rhamnetin Exhibits Anti‐Tuberculosis Activity and Protects against Lung Inflammation
Authors: Kim Min Jun , Jeon Dasom , Kwak Chulhee , Ryoo Sungweon , Kim Yangmee
Published: September 2016

Rhamnetin, a natural flavonoid found in cloves and berries has been reported to show anti‐inflammatory activities in lipopolysaccharide‐stimulated RAW264.7 cells and may be a potent inhibitor for extracellular signal‐regulated kinase 1 (ERK1) and c‐Jun N‐terminal kinase. Here, we showed that rhamnetin has antimycobacterial effects on Mycobacterium tuberculosis (MT) H37Rv, multi‐drug‐, and extensively drug‐resistant clinical isolates. We also investigated the effect of rhamnetin on interferon (IFN)‐γ‐stimulated human lung fibroblast MRC‐5 cells, since MT infection causes intensive lung inflammation. Rhamnetin suppressed mRNA levels of tumor necrosis factor‐α, interleukin (IL)‐1β, IL‐6, IL‐12, and matrix metalloproteinase‐1. Furthermore, it inhibited IFN‐γ‐mediated stimulation of ERK1 and p38 mitogen‐activated protein kinase in MRC‐5 cells. These results showed that rhamnetin has potent anti‐tuberculosis activities and effectively suppresses lung inflammation, implying that rhamnetin can be a potent anti‐tuberculosis dietary agent.
Glycosylation of monoclonal antibody products: Current status and future prospects
Authors: Batra Jyoti , Rathore Anurag S.
Published: September 2016

Protein based therapeutics have started to dominate the pharmaceutical landscape primarily due to the high efficacy that they have demonstrated against complex diseases. Despite the significant success, issues with regards to safety, efficacy and quality of biotherapeutics have been a point of considerable debate and concern among the various stakeholders. The correlation between the glycoform profile and the safety and efficacy of a drug, in particular, has garnered significant attention of researchers worldwide. An escalated emphasis is presently given to develop an understanding of how the various process parameters as well molecular biology considerations contribute to glycan heterogeneity. This paper aims to review the major developments that have occurred in this area over the last decade. The impact of the various process parameters on glycan expression, methods for obtaining a pre‐determined glycan levels/profiles of a protein therapeutic and developments in the area of real‐time glycan monitoring and control are discussed. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1091–1102, 2016
Effect of green and red light in lipid accumulation and transcriptional profile of genes implicated in lipid biosynthesis in Chlamydomonas reinhardtii
Authors: Gaytán‐Luna Daniel Eugenio , Ochoa‐Alfaro Ana Erika , Rocha‐Uribe Alejandro , Pérez‐Martínez Ana Silvia , Alpuche‐Solís Ángel Gabriel , Soria‐Guerra Ruth Elena
Published: September 2016

Microalgae have the potential to accumulate triacylglycerols under different light spectra. In this work, Chlamydomonas reinhardtii was grown under white (400–700 nm), red (650 nm), and green (550 nm) lights. According to our results, red light (650 nm) has a positive effect in the microalgae growth and chlorophyll concentration. About the lipid content, the control culture (white light‐illuminated) reached a 4.4% of dry cell weight (dcw), whereas the culture grown at 550 nm showed an increase of 1.35‐fold in the lipids accumulation (5.96% dcw). Interestingly, the most significant accumulation was found in the culture grown at 650 nm (14.78% dcw) which means 3.36‐fold higher with respect to the white light‐illuminated culture. The most abundant fatty acids found in lipid extracts obtained from the cultures under different light wavelength were palmitic (C16: 0), oleic (C18: 1n9), stearidonic (C18: 4), and linoleic (C18: 2), which are useful in the biodiesel production. Changes in gene expression in response to different wavelength illuminations were assessed; however, an in‐depth analysis of a larger number of genes involved in lipid biosynthesis is necessary to fully explain the highest accumulation of lipids in the culture grown under red light. This approach will be useful to find a sustainable source of lipids for biodiesel production. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1404–1411, 2016
Bone marrow sarcoidosis associated with long‐term interferon‐β treatment for multiple sclerosis
Authors: Teh Angela , Russell Patrick , Li Jordan , Hewage Udul
Published: September 2016

Key Clinical Message

Sarcoidosis is a diagnosis that should be considered in patients receiving interferon therapy, who present with anemia and multiorgan dysfunction regardless of the duration of their treatment. When sarcoidosis is suspected, bone marrow biopsy should be considered especially for cases predominant by extrapulmonary features.
Pharmacist blood pressure management programs using telemonitoring systems are useful for monitoring side effects of antihypertensive drugs in a community pharmacy
Authors: Mizuno Tomohiro , Nabetani Nobuko , Yamashita Natsuki , Matsumoto Chizuru , Yasuda Yoshinari , Nagamatsu Tadashi , Umemura Norimasa
Published: September 2016

Key Clinical Message

We previously started pharmacist blood pressure (BP) management programs using telemonitoring systems for monitoring side effects of antihypertensive drugs in a community pharmacy. The present case demonstrates that pharmacist BP management programs using telemonitoring systems are useful for monitoring side effects of antihypertensive drugs in a community pharmacy.
A Synthesis of Exiguaquinol Dessulfate
Authors: Schwarzwalder Gregg M. , Scott David R. , Vanderwal Christopher D.
Published: September 2016

A concise and stereoselective synthesis of exiguaquinol dessulfate is described. Sequential application of a Diels–Alder cycloaddition, a desymmetrizing aldol addition, and a reductive Heck cyclization established most of the architecture of exiguaquinol, and a carefully choreographed introduction of the polar substituents afforded the title compound; unfortunately, naphthoquinol sulfation could not be achieved to deliver exiguaquinol. Our hypothesis regarding the configurational preference of the N‐acyl hemiaminal, which was based upon an analysis of internal hydrogen‐bonding interactions with polar functional groups, was proven correct. A late‐stage intermediate did not demonstrate bactericidal activity against H. pylori cultures.
A combined biomarker and clinical panel for chronic graft versus host disease diagnosis
Authors: Pidala Joseph , Sigdel Tara K , Wang Anyou , Hsieh Sue , Inamoto Yoshi , Martin Paul J , Flowers Mary ED , Hansen John A , Lee Stephanie J , Sarwal Minnie M
Published: September 2016

Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi‐centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non‐GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0‐3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers.
Pancreatic neuroendocrine microadenomatosis: A case report of cytology and histology correlation
Authors: Vo Nguyen , Cohen David W. , Dillhoff Mary E. , Jin Ming
Published: September 2016

Pancreatic neuroendocrine neoplasia is categorized by grade, size, and functional status. Neuroendocrine microadenoma (NEMA) is defined as a neuroendocrine tumor (NET) that measures less than 0.5 cm in diameter. Multiple NEMAs are termed neuroendocrine adenomatosis (NEMAtosis). The surgical pathology and clinical aspects of pancreatic NEMAtosis have been reported, but there has been no report regarding EUS‐FNA cytology of NEMAtosis. We report a case of NEMAtosis with cytologic correlation and illustrate the diagnostic challenges and potential pitfalls. The pre‐operative cytology can be problematic. The main differential diagnosis of the EUS‐FNA specimen includes NET, normal pancreas, and islet cell hyperplasia/aggregation associated with chronic pancreatitis. The helpful cytopathologic feature of NEMAtosis is the presence of two intermingled populations of loosely‐cohesive neuroendocrine cell clusters and tight acinar cell groups arranged in microacinar and/or grape‐like structures. Although neuroendocrine cells and acinar cells possess different cytomorphology, the distinction is not always straightforward because both types of cells are small and cytologically bland. Cytologic assessment of both architecture and individual cell morphology is imperative to avoid interpretation error and further guide appropriate clinical management. Diagn. Cytopathol. 2017;45:143–147. © 2016 Wiley Periodicals, Inc.
Yes, We Can!
Authors: Férey Gérard
Published: September 2016

The passage to applications is a new challenge for MOFs and PCPs. The immense knowledge acquired in academic science deserves a new step, more than just to increase the number of MOFs and PCPs. From his own experience, Gérard Férey analyzes the supplementary factors necessary for a smooth from passage from preparation to applications.
Comparative evaluation of biogas production from dairy manure and co‐digestion with maize silage by CSTR and new anaerobic hybrid reactor
Authors: Varol Ayhan , Ugurlu Aysenur
Published: September 2016

This study aimed to investigate potential methane production through anaerobic digestion of dairy manure and co‐digestion with maize silage. Two different anaerobic reactor configurations (single‐stage continuously stirred tank reactor [CSTR] and hybrid anaerobic digester) were used and biogas production performances for each reactor were compared. The HR was planned to enable phase separation in order to improve process stability and biogas production under higher total solids loadings (≥4%). The systems were tested under six different organic loading rates increased steadily from 1.1 to 5.4 g VS/L.d. The CSTR exhibited lower system stability and biomass conversion efficiency than the HR. The specific biogas production of the hybrid system was between 440 and 320 mL/gVS with 81–65% volatile solids (VS) destruction. The hybrid system provided 116% increase in specific biogas production and VS destruction improved by more than 14%. When MS was co‐digested together with dairy manure, specific biogas production rates increased about 1.2‐fold. Co‐digestion was more beneficial than mono‐material digestion. The hybrid system allowed for generating methane enriched biogas (>75% methane) by enabling phase separation in the reactor. It was observed that acidogenic conditions prevailed in the first two compartments and the following two segments as methanogenic conditions were observed. The pH of the acidogenic part ranged between 4.7 and 5.5 and the methanogenic part was between 6.8 and 7.2.
Not all that glitters is gold: A guide to critical appraisal of animal drug trials in epilepsy
Authors: Galanopoulou Aristea S. , Mowrey Wenzhu B.
Published: September 2016

Preclinical studies have produced numerous drugs with antiseizure properties that currently are the standard of care. One third of the human population with epilepsy still continues to have seizures despite the ongoing discoveries. The recognized clinical gaps of care that need to be addressed are the identification of antiepileptogenic and disease‐modifying treatments, and treatments for refractory seizures or for seizures and epilepsies with limited or unsatisfactory treatments, such as early life epileptic encephalopathies. In this invited review, we provide a historical summary of the international efforts to reevaluate the strategies adopted in preclinical epilepsy therapy discovery studies. We discuss issues that may affect the quality, interpretation, and validation of preclinical studies and their translation to successful therapies for humans affected with epilepsy. These include the selection of animal models and the study design; research practices that affect rigor (such as appropriate use of statistics and reporting of study methods and results, their validation across models, labs, and preclinical‐clinical studies); the need to harmonize research methods and outcome assessment; and the importance of improving translation to clinically appropriate situations. The epilepsy research community is incrementally adopting collaborative research, including consortia or multicenter studies to meet these needs. Improving the infrastructure that can support these efforts will be instrumental in future success.
Responses of juvenile southern flounder exposed to Deepwater Horizon oil-contaminated sediments
Authors: Brown-Peterson Nancy J. , Krasnec Michelle O. , Lay Claire R. , Morris Jeffrey M. , Griffitt Robert J.
Published: September 2016

The Deepwater Horizon oil spill released millions of barrels of crude oil into the northern Gulf of Mexico, much of which remains associated with sediments and can have continuing impacts on biota. Juvenile southern flounder (Paralichthys lethostigma) were exposed for 28 d in the laboratory under controlled conditions to reference and Deepwater Horizon oil-contaminated sediments collected from coastal Louisiana to assess the impacts on an ecologically and commercially important benthic fish. The measured polycyclic aromatic hydrocarbon (PAH) concentrations in the sediments ranged from 0.25 mg/kg to 3940 mg/kg suite of 50 PAH analytes (tPAH50). Mortality increased with both concentration and duration of exposure. Exposed flounder length and weight was lower compared to controls after 28 d of exposure to the sediments with the highest PAH concentration, but condition factor was significantly higher in these fish compared with all other treatments. Histopathological analyses showed increased occurrence of gill abnormalities, including telangiectasis, epithelial proliferation, and fused lamellae in flounder exposed to sediments with the highest tPAH50 concentrations. In addition, hepatic vascular congestion and macrovesicular vacuolation were observed in flounder exposed to the more contaminated sediments. These data suggest that chronic exposure to field collected oil-contaminated sediments results in a variety of sublethal impacts to a benthic fish, with implications for long-term recovery from oil spills. Environ Toxicol Chem 2017;36:1067–1076. © 2016 SETAC
Effective inter‐symbol interference mitigation with a limited amount of enzymes in molecular communications
Authors: Cho Yae Jee , Yilmaz H. Birkan , Guo Weisi , Chae Chan‐Byoung
Published: September 2016

In molecular communication via diffusion (MCvD), the inter‐symbol interference (ISI) is a well‐known severe problem that deteriorates both data‐rate and link reliability. ISI mainly occurs because of the slow and highly random propagation of the messenger molecules, which causes the emitted molecules from the previous symbols to interfere with molecules from the current symbol. An effective way to mitigate the ISI is using enzymes to degrade undesired molecules. Prior work on ISI mitigation by enzymes has assumed an infinite amount of enzymes randomly distributed around the molecular channel. Taking a different approach, this paper assumes an MCvD channel with a limited amount of enzymes. The main question this paper addresses is how to deploy these enzymes in an effective structure so that ISI mitigation is maximized. To find an effective MCvD channel environment, this study considers optimization of the shape of the transmitter node, the deployment location and structure, the size of the enzyme deployed area, and the half‐lives of the enzymes. It also analyzes the dependence of the optimum size of the enzyme area on the distance and half‐life. Lastly, the paper yields interesting results regarding the actual shape of the enzyme region itself.
Validity of using ad hoc methods to analyze secondary traits in case‐control association studies
Authors: Yung Godwin , Lin Xihong
Published: September 2016

Case‐control association studies often collect from their subjects information on secondary phenotypes. Reusing the data and studying the association between genes and secondary phenotypes provide an attractive and cost‐effective approach that can lead to discovery of new genetic associations. A number of approaches have been proposed, including simple and computationally efficient ad hoc methods that ignore ascertainment or stratify on case‐control status. Justification for these approaches relies on the assumption of no covariates and the correct specification of the primary disease model as a logistic model. Both might not be true in practice, for example, in the presence of population stratification or the primary disease model following a probit model. In this paper, we investigate the validity of ad hoc methods in the presence of covariates and possible disease model misspecification. We show that in taking an ad hoc approach, it may be desirable to include covariates that affect the primary disease in the secondary phenotype model, even though these covariates are not necessarily associated with the secondary phenotype. We also show that when the disease is rare, ad hoc methods can lead to severely biased estimation and inference if the true disease model follows a probit model instead of a logistic model. Our results are justified theoretically and via simulations. Applied to real data analysis of genetic associations with cigarette smoking, ad hoc methods collectively identified as highly significant () single nucleotide polymorphisms from over 10 genes, genes that were identified in previous studies of smoking cessation.
Paracrine sonic hedgehog signaling contributes significantly to acquired steroidogenesis in the prostate tumor microenvironment
Authors: Lubik Amy A. , Nouri Mannan , Truong Sarah , Ghaffari Mazyar , Adomat Hans H. , Corey Eva , Cox Michael E. , Li Na , Guns Emma S. , Yenki Parvin , Pham Steven , Buttyan Ralph
Published: September 2016

Despite the substantial benefit of androgen deprivation therapy (ADT) for metastatic prostate cancer, patients often progress to castration‐resistant disease (CRPC) that is more difficult to treat. CRPC is associated with renewed androgen receptor activity in tumor cells and restoration of tumor androgen levels through acquired intratumoral steroidogenesis (AIS). Although prostate cancer (PCa) cells have been shown to have steroidogenic capability in vitro, we previously found that benign prostate stromal cells (PrSCs) can also synthesize testosterone (T) from an adrenal precursor, DHEA, when stimulated with a hedgehog (Hh) pathway agonist, SAG. Here, we show exposure of PrSCs to a different Smoothened (Smo) agonist, Ag1.5, or to conditioned medium from sonic hedgehog overexpressing LNCaP cells induces steroidogenic enzyme expression in PrSCs and significantly increases production of T and its precursor steroids in a Smo‐dependent manner from 22‐OH‐cholesterol substrate. Hh agonist‐/ligand‐treated PrSCs produced androgens at a rate similar to or greater than that of PCa cell lines. Likewise, primary bone marrow stromal cells became more steroidogenic and produced T under the influence of Smo agonist. Treatment of mice bearing LNCaP xenografts with a Smo antagonist, TAK‐441, delayed the onset of CRPC after castration and substantially reduced androgen levels in residual tumors. These outcomes support the idea that stromal cells in ADT‐treated primary or metastatic prostate tumors can contribute to AIS as a consequence of a paracrine Hh signaling microenvironment. As such, Smo antagonists may be useful for targeting prostate tumor stromal cell‐derived AIS and delaying the onset of CRPC after ADT.
Simultaneous quantification of triterpenoid saponins in rat plasma by UHPLC–MS/MS and its application to a pharmacokinetic study after oral total saponin of Aralia elata leaves
Authors: Sun Yichun , Xue Juan , Li Baimei , Lin Xiaoting , Wang Zhibin , Jiang Hai , Zhang Hongwei , Wang Qiuhong , Kuang Haixue
Published: September 2016

A rapid, sensitive, and reliable analytical ultra performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of Aralia‐saponin IV, 3‐O‐β‐d‐glucopyranosyl‐(1→3)‐β‐d‐glucopyranosyl‐(1→3)‐β‐d‐glucopyranosyl oleanolic acid 28‐O‐β‐d‐glucopyranoside, Aralia‐saponin A and Aralia‐saponin B after the oral administration of total saponin of Aralia elata leaves in rat plasma. Plasma samples were pretreated by protein precipitation with methanol. The analysis was performed on an ACQUITY UPLC HSS T3 column. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using an electrospray ionization source with negative ionization mode. Under the experimental conditions, the calibration curves of four analytes had good linearity values (r > 0.991). The intra‐ and inter‐day precision values of the four analytes were ≤ 11.6%, and the accuracy was between –6.2 and 4.2%.The extraction recoveries of four triterpenoid saponins were in the range of 84.06–91.66% (RSD < 10.5%), and all values of the matrix effect were more than 90.30%. The developed analytical method was successfully applied to pharmacokinetic study on simultaneous determination of the four triterpenoid saponins in rat plasma after oral administration of total saponin of Aralia elata leaves, which helps guiding clinical usage of Aralia elata leaves.
Cationic Main‐Chain Polyelectrolytes with Pyridinium‐Based p‐Phenylenevinylene Units and Their Aggregation‐Induced Gelation
Authors: Samanta Suman Kalyan , Scherf Ullrich
Published: September 2016

Cationic polyelectrolytes find potential applications in electronic device fabrication, biosensing as well as in biological fields. Herein, a series of cationic main‐chain polyelectrolytes with pyridinium‐based p‐phenylenevinylene units that are connected via alkylene spacers of varying lengths are synthesized by a base‐catalyzed aldol‐type coupling reaction. Their mean average molecular weights range from 15 000 to 32 000 g mol‐1, corresponding to about 16–33 repeat units. Due to the presence of alkyl side‐chains and alkylene spacers as well as cationic hard‐charges the polymers are endowed with amphiphilic character and hence, aggregation of these polyelectrolytes at high concentration leads to thermoreversible physical gel formation in dimethyl sulfoxide accompanied by interchain interactions. Morphological analysis shows spherical aggregates in case of C16‐Poly‐S12 in dimethyl sulfoxide. Dependence of gelation behavior on the length of alkyl side‐chains and alkylene spacers of the polyelectrolytes are addressed.

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Influence of the Polymeric Matrix and Thermal Treatment on the Properties of Polyolefin‐Graphite Nanosheets Nanocomposites
Authors: González Darío M. , Quijada Raúl , Yazdani‐Pedram Mehrdad , Benavente Rosario , Galland Griselda B. , Milani Marcéo A.
Published: September 2016

Homo and copolymers of metallocenic poly(propylene) with 1‐hexene and 1‐octadecene are used to prepare nanocomposites via melt mixing by using graphite nanosheets (GNSs) as filler. Different amounts of GNSs are used in order to study the influence of the filler on the thermal, mechanical, and electrical properties of nanocomposites. Significant changes have been observed in the crystallization temperature (Tc) of the nanocomposites. Thermogravimetric analysis shows improvement in thermal stability. Young's modulus and elongation at break of the nanocomposites are depended on the type of the matrix and the amount of GNSs. Materials with high flexibility are obtained in the cases of matrices based on copolymers even at high filler loading. Nanocomposites have become a semiconductor material reaching conductivity of 10−4 S cm−1. Two different thermal treatments have been applied in the preparation of the films by compression molding. X‐ray diffraction analysis shows the existence of polymorphism according to the thermal treatment applied.

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Linear, Star, and Comb Oxidation‐Responsive Polymers: Effect of Branching Degree and Topology on Aggregation and Responsiveness
Authors: d'Arcy Richard , Gennari Arianna , Donno Roberto , Tirelli Nicola
Published: September 2016

Families of amphiphilic oxidation‐responsive polymers (poly(ethylene glycol)‐polysulfides) with different architectures (linear, 4, 6, and 8‐armed stars and 10, 15, and 20‐armed combs) and compositions (variable ethylene sulfide/propylene sulfide ratio) are prepared. In water, all the polymers assemble in spherical micelles, with critical micellar concentrations <0.01 mg mL−1 for all the branched polymers. Triple‐detection gel permeation chromatography (GPC) and asymmetric field flow fractionation (AFFF) with dynamic and static light scattering detection, respectively, show an increasing compaction of the polymeric coil and a strong reduction of the aggregation number with increasing degree of branching. The key finding of this study is that the kinetics of the oxidative response sharply depend on the branching; in particular, it is highlighted that the degree of branching influences the lag time before a response can be observed rather than the speed of the response itself, a phenomenon that is attributed to a branching‐dependent solubility of the oxidant in the polysulfide matrix.

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Local and global results for modified Szász–Mirakjan operators
Authors: Gandhi R.B. ,   Deepmala, Mishra Vishnu Narayan
Published: September 2016

In this paper, we study a natural modification of Szász–Mirakjan operators. It is shown by discussing many important established results for Szász–Mirakjan operators. The results do hold for this modification as well, be they local in nature or global, be they qualitative or quantitative. It is also shown that this generalization is meaningful by means of examples and graphical representations. Copyright © 2016 John Wiley & Sons, Ltd.
Evaluation of renal oxygenation change under the influence of carbogen breathing using a dynamic R2, R2′ and R2* quantification approach
Authors: Wang Chengyan , Zhao Kai , Zhang Rui , Jiang Li , Wang Rui , Zhang Xiaodong , Wang He , Jin Lixin , Zhang Jue , Wang Xiaoying , Fang Jing
Published: September 2016

The purpose of this study is to demonstrate the feasibility of dynamic renal R2/R2′/R2* measurements based on a method, denoted psMASE‐ME, in which a periodic 180° pulse‐shifting multi‐echo asymmetric spin echo (psMASE) sequence, combined with a moving estimation (ME) strategy, is adopted. Following approval by the institutional animal care and use committee, a block design of respiratory challenge with interleaved air and carbogen (97% O2, 3% CO2) breathing was employed in nine rabbits. Parametrical R2/R2′/R2* maps were computed and average R2/R2′/R2* values were measured in regions of interest in the renal medulla and cortex. Bland–Altman plots showed good agreement between the proposed method and reference standards of multi‐echo spin echo and multi‐echo gradient echo sequences. Renal R2, R2′ and R2* decreased significantly from 16.2 ± 4.4 s−1, 9.8 ± 5.2 s−1 and 25.9 ± 5.0 s−1 to 14.9 ± 4.4 s−1 (p < 0.05), 8.5 ± 4.1 s−1 (p < 0.05) and 23.4 ± 4.8 s−1 (p < 0.05) in the cortex when switching the gas mixture from room air to carbogen. In the renal medulla, R2, R2′ and R2* also decreased significantly from 12.9 ± 4.7 s−1, 15.1 ± 5.8 s−1 and 27.9 ± 5.3 s−1 to 11.8 ± 4.5 s−1 (p < 0.05), 14.2 ± 4.2 s−1 (p < 0.05) and 25.8 ± 5.1 s−1 (p < 0.05). No statistically significant differences in relative R2, R2′ and R2* changes were observed between the cortex and medulla (p = 0.72 for R2, p = 0.39 for R2′ and p = 0.61 for R2*). The psMASE‐ME method for dynamic renal R2/R2′/R2* measurements, together with the respiratory challenge, has potential use in the evaluation of renal oxygenation in many renal diseases
Measuring child personality when child personality was not measured: Application of a thin‐slice approach
Authors: Tackett Jennifer L. , Smack Avanté J. , Herzhoff Kathrin , Reardon Kathleen W. , Daoud Stephanie , Granic Isabela
Published: September 2016

Recent efforts have demonstrated that thin‐slice (TS) assessment—or assessment of individual characteristics after only brief exposure to that individual's behaviour—can produce reliable and valid measurements of child personality traits. The extent to which this approach can be generalized to archival data not designed to measure personality, and whether it can be used to measure personality pathology traits in youth, is not yet known. Archival video data of a parent–child interaction task was collected as part of a clinical intervention trial for aggressive children (N = 177). Unacquainted observers independently watched the clips and rated children on normal‐range (neuroticism, extraversion, agreeableness, conscientiousness and openness to experience) and pathological (callous–unemotional) personality traits. TS ratings of child personality showed strong internal consistency, valid associations with measures of externalizing problems and temperament, and revealed differentiated subgroups of children based on severity. As such, these findings demonstrate an ecologically valid application of TS methodology and illustrate how researchers and clinicians can extend their existing data by measuring child personality using TS methodology, even in cases where child personality was not originally measured. Copyright © 2016 John Wiley & Sons, Ltd.
Atmospheric pressure roll‐to‐roll plasma enhanced CVD of high quality silica‐like bilayer encapsulation films
Authors: Elam Fiona M. , Starostin Sergey A. , Meshkova Anna S. , van der Velden‐Schuermans Bernadette C. A. M. , Bouwstra Jan B. , van de Sanden Mauritius C. M. , de Vries Hindrik W.
Published: September 2016

A glow like atmospheric pressure dielectric barrier discharge in a roll‐to‐roll setup was used to synthesize 90 nm silica‐like bilayer encapsulation films composed of a 30 nm dense “barrier layer” and a comparatively less dense 60 nm “buffer layer” onto a polyethylene 2,6 naphthalate substrate by means of plasma enhanced chemical vapor deposition. Tetraethyl orthosilicate was used as the precursor gas, together with a mixture of nitrogen, oxygen, and argon. The microstructure, chemical composition, morphology, and permeation properties of the films were studied as a function of the specific energy delivered per precursor molecule, and oxygen concentration in the gas mixture, during the deposition of the barrier layer. The presence of the buffer layer within the bilayer architecture critically enhanced the encapsulation performance of the bilayer films, and this in conjunction with increasing the specific energy delivered per precursor molecule during the barrier layer deposition to a value of 20 keV, enabled an effective water vapor transmission rate as low as 6.9 × 10−4 g m−2 d−1 (at 40 °C, 90% relative humidity (RH)) to be achieved. Furthermore, the bilayer film structure has given rise to a remarkable 50% reduction in deposition energy consumption per barrier area with respect to single layer silica‐like films of equivalent encapsulation performance and thickness.
Crystal structure of nonphosphorylated receiver domain of the stress response regulator RcsB from Escherichia coli
Authors: Filippova Ekaterina V. , Wawrzak Zdzislaw , Ruan Jiapeng , Pshenychnyi Sergii , Schultz Richard M. , Wolfe Alan J. , Anderson Wayne F.
Published: September 2016

RcsB, the transcription‐associated response regulator of the Rcs phosphorelay two‐component signal transduction system, activates cell stress responses associated with desiccation, cell wall biosynthesis, cell division, virulence, biofilm formation, and antibiotic resistance in enteric bacterial pathogens. RcsB belongs to the FixJ/NarL family of transcriptional regulators, which are characterized by a highly conserved C‐terminal DNA‐binding domain. The N‐terminal domain of RcsB belongs to the family of two‐component receiver domains. This receiver domain contains the phosphoacceptor site and participates in RcsB dimer formation; it also contributes to dimer formation with other transcription factor partners. Here, we describe the crystal structure of the Escherichia coli RcsB receiver domain in its nonphosphorylated state. The structure reveals important molecular details of phosphorylation‐independent dimerization of RcsB and has implication for the formation of heterodimers.
Efficacy and safety evaluation of claudin‐4‐targeted antitumor therapy using a human and mouse cross‐reactive monoclonal antibody
Authors: Hashimoto Yosuke , Kawahigashi Yumi , Hata Tomoyuki , Li Xiangru , Watari Akihiro , Tada Minoru , Ishii‐Watabe Akiko , Okada Yoshiaki , Doi Takefumi , Fukasawa Masayoshi , Kuniyasu Hiroki , Yagi Kiyohito , Kondoh Masuo
Published: September 2016

Claudin‐4 (CLDN‐4), a tight‐junction protein, is overexpressed in various malignant tumors, including gastric, colorectal, pancreatic, and breast cancers. However, CLDN‐4 is also expressed in normal tissues, including the liver, pancreas, kidney, and small intestine. Whether CLDN‐4 is an effective and safe target for cancer therapy has been unclear owing to the lack of a binder with both CLDN‐4 specificity and cross‐reactivity to human and murine cells. In this study, we successfully generated a rat anti‐CLDN‐4 monoclonal antibody (5D12) that was specific to, and cross‐reactive with, human and mouse CLDN‐4. 5D12 recognized the second extracellular domain of human CLDN‐4 in a conformation‐dependent manner. A human–rat chimeric IgG1 of 5D12 (xi‐5D12) activated the FcγIIIa receptor, indicating the activation of antibody‐dependent cellular cytotoxicity in CLDN‐4‐expressing cells. Moreover, xi‐5D12 significantly suppressed tumor growth in mice bearing human colorectal and gastric tumors without apparent adverse effects, such as weight loss or liver and kidney damage. These results suggest that CLDN‐4 is a potent target for cancer therapy and that an anti‐CLDN‐4 antibody is a promising candidate anticancer agent.
Engineering the interface characteristics on the enhancement of field electron emission properties of vertically aligned hexagonal boron nitride nanowalls
Authors: Sankaran K. J. , Hoang D. Q. , Srinivasu K. , Korneychuk S. , Turner S. , Drijkoningen S. , Pobedinskas P. , Verbeeck J. , Leou K. C. , Lin I. N. , Haenen K.
Published: September 2016

Utilization of Au and nanocrystalline diamond (NCD) as interlayers noticeably modifies the microstructure and field electron emission (FEE) properties of hexagonal boron nitride nanowalls (hBNNWs) grown on Si substrates. The FEE properties of hBNNWs on Au could be turned on at a low turn‐on field of 14.3 V μm−1, attaining FEE current density of 2.58 mA cm−2 and life‐time stability of 105 min. Transmission electron microscopy reveals that the Au‐interlayer nucleates the hBN directly, preventing the formation of amorphous boron nitride (aBN) in the interface, resulting in enhanced FEE properties. But Au forms as droplets on the Si substrate forming again aBN at the interface. Conversely, hBNNWs on NCD shows superior in life‐time stability of 287 min although it possesses inferior FEE properties in terms of larger turn‐on field and lower FEE current density as compared to that of hBNNWs‐Au. The uniform and continuous NCD film on Si also circumvents the formation of aBN phases and allows hBN to grow directly on NCD. Incorporation of carbon in hBNNWs from the NCD‐interlayer improves the conductivity of hBNNWs, which assists in transporting the electrons efficiently from NCD to hBNNWs that results in better field emission of electrons with high life‐time stability.
Self‐consistent Purcell factor and spontaneous topological transition in hyperbolic metamaterials
Authors: Krasikov Sergey , Iorsh Ivan V.
Published: September 2016

In this work, we develop a self‐consistent approach for calculation of the Purcell factor and Lamb shift in highly dispersive hyperbolic metamaterial accounting for the effective dipole frequency shift. Also we theoretically predict the possi‐ bility of spontaneous topological transition, which occurs not due to the external change of the system parameters but only due to the Lamb shift.
Value-creating organizational leadership
Authors: Kollenscher Eldad , Popper Micha , Ronen Boaz
Published: September 2016

Despite their many contributions, each of the most prevalent approaches to leadership – the micro interpersonal leadership models such as transformational theory, trait theory and charismatic leadership, and the macro strategic management – has notable ‘blind spots’ and relies on biased or partial assumptions. Furthermore, the macro–micro polarization of major leadership theories overlooks important meso perspective processes, such as structuring, which leaders can use to attain a more compounded and sustained effect on organizational outcomes. The goal of this paper is to propose an integrative theoretical framework – value-creating leadership – which provides what is missing from the theory of organizational leadership. Value-creating leadership combines micro and macro perspectives regarding management and leadership along with a meso perspective to create a unified model of corporate leadership.
Non-Strongyloides rhabditida identified in fecal samples – two case reports: lessons learned from morphological and molecular diagnostic approaches
Authors: STACHURSKA-HAGEN TERESA , JOHNSEN OLE HARALD , ROBERTSON LUCY J.
Published: September 2016

Nematodes in the order Rhabditida, including species ofStrongyloidesandPelodera, may be parasites of domestic animals. In this paper, we describe two apparent cases of rhabditid infections, one in a dog and one in a litter of piglets. The dog infection was originally considered likely to be an infection withStrongyloides, based on superficial morphological examination and PCR results without sequencing. However, more careful morphological analysis and inclusion of several molecular analyses, including sequencing, revealed that an infection withPeloderasp. was more likely, probablyPelodera pseudoteres. Treatment with fenbendazole and selamectin was apparently successful. Similarly, based on both morphological and molecular analyses the apparent piglet infections were considered most likely to be withRhabditisspp., possiblyRhabditis axei. The detection of larvae of nematodes in the order Rhabditida in fecal samples, particularly from dogs, may easily be considered as being indicative ofStrongyloidesinfection. Given the zoonotic potential of canineStrongyloides, correct diagnosis is important. However, as illustrated by these two cases, careful morphological examination and measurement, supported by full molecular investigations, including sequencing, are essential in order to avoid this misdiagnosis.