bluuebunny/crossref_metadata_2025 huggingface dataset:
Boron‐Based Inhibitors of Acyl Protein Thioesterases 1 and 2
Authors: Zimmermann Tobias J. , Bürger Marco , Tashiro Etsu , Kondoh Yasumitsu , Martinez Nancy E. , Görmer Kristina , Rosin‐Steiner Sigrid , Shimizu Takeshi , Ozaki Shoichiro , Mikoshiba Katsuhiko , Watanabe Nobumoto , Hall Dennis , Vetter Ingrid R. , Osada Hiroyuki , Hedberg Christian , Waldmann Herbert
Published: December 2012

Ras proteins are of importance in cell proliferation, and hence their mutated forms play causative roles in many kinds of cancer in different tissues. Inhibition of the Ras‐depalmitoylating enzyme acyl protein thioesterases APT1 and ‐2 is a new approach to modulating the Ras cycle. Here we present boronic and borinic acid derivatives as a new class of potent and nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays and turned out to inhibit human APT1 and ‐2 in a competitive mode. Furthermore, one of the molecules was demonstrated to inhibit Erk1/2 phosphorylation significantly.
A Synthetic, Species‐Specific Activator of Secondary Metabolism and Sporulation in Streptomyces coelicolor
Authors: Ahmed Salman , Craney Arryn , Pimentel‐Elardo Sheila M. , Nodwell Justin R.
Published: December 2012

The secondary metabolites produced by bacterial species serve many clinically useful purposes, and Streptomyces have been an abundant source of such compounds. However, a poor understanding of their regulatory cascades leads to an inability to isolate all of the secondary metabolites this genus is capable of producing. This study focuses on comparing synthetic small molecules that were found to alter the production of secondary metabolites in Streptomyces coelicolor. A survey of these molecules suggests that each has a distinct mechanism of action, and hence, could be used as a unique probe of secondary metabolism. A comparative analysis of two of these molecules, ARC2 and ARC6, confirmed that they modulate secondary metabolites in different ways. In a separate study, ARC2 was shown to give rise to a different phenotype through the inhibition of a target in fatty acid biosynthesis. The results of this study suggest that ARC6 does not have the same target, although it might target the same metabolic system. Furthermore, the results demonstrate that ARC2 and ARC6 act through distinct mechanisms and further suggest that chemical probes can be important tools in enhancing our understanding of secondary metabolism and the streptomycete life cycle.
Numerical and Experimental Study of Catalyst Loading and Body Effects on a Gas‐Liquid Trickle‐Flow Bed
Authors: Salimi M. , Hashemabadi S. H. , Noroozi S. , Heidari A. , Bazmi M.
Published: December 2012

The influence of tortuosity and fluid volume fractions on trickle‐flow bed performance was analyzed. Hydrodynamics of the gas‐liquid downward flow through trickle beds, filled with industrial trilobe catalysts, were investigated experimentally and numerically. The pressure drop and liquid holdup were measured at different gas and liquid velocities and in two different loading methods, namely, sock and dense catalyst loading. The effect of sharp corners on hydrodynamic parameters was considered in a bed with rectangular cross section. The reactor was simulated, considering a three‐phase model, appropriate porosity function, and interfacial forces based on the Eulerian‐Eulerian approach. Computational fluid dynamics (CFD) simulation results for pressure drop and liquid holdup agreed well with experimental data. Finally, the velocity distribution in two types of loading and the effect of bed geometry in CFD results demonstrated that pressure drop and liquid holdup were reduced compared to a cylindrical one due to high voidage at sharp corners.
Biomimetic Synthesis of a Water‐Soluble Conducting Polymer of 3,4‐Ethylene‐dioxythiophene
Authors: Nabid M. R. , Shamsianpour M. , Sedghi R. , Moghaddam A. B. , Asadi S. , Osati S. , Safari N.
Published: December 2012

A novel biomimetic route for the synthesis of a water‐soluble poly(3,4‐ethylenedioxithiophene) (PEDT) in the presence of poly(styrene sulfonate) (PSS) and using iron(III)‐tetra(p‐sulfonatophenyl)porphyrin (FeIIITSPP), cobalt(III)‐tetra(p‐sulfonatophenyl)porphyrin (CoIIITSPP), manganese(III)‐tetra(p‐sulfonatophenyl)porphyrin (MnIIITSPP), and copper(II)‐tetra(p‐sulfonatophenyl)porphyrin (CuIITSPP) as effective catalysts is presented. The reactions were performed with different monomer, catalyst, template, and initiator concentrations. The absorbance of the polaron bands at various pH values indicated pH 2 as the best condition for polymerization. Precipitation or salting out was highly dependent on the mentioned factors. The formation of PEDT was confirmed by UV‐Vis and FT‐IR spectroscopy. Cyclic voltammetry proved the convenient electroactivity of the synthesized polymer. The presence of PSS that serves as a charge‐compensating dopant provides processability and water solubility and, in addition, a distinct advantage over similar reactions employing native enzymes due to higher stability and lower cost of the catalysts.
pH‐Dependent Coordination of AgI Ions by Histidine: Experiment, Theory, and a Model for SilE
Authors: Mirolo Laurent , Schmidt Tobias , Eckhardt Sonja , Meuwly Markus , Fromm Katharina M.
Published: December 2012

Artificial implants and biomaterials lack the natural defense system of our body and, thus, have to be protected from bacterial adhesion and biofilm formation. In addition to the increasing number of implanted objects, the resistance of bacteria is also an important problem. Silver ions are well‐known for their antimicrobial properties, yet not a lot is known about their mode of action. Silver is expected to interact on many levels, thus the development of silver resistance is very difficult. Nevertheless, some bacteria are able to resist silver, even at higher concentrations. One such defense mechanism of bacteria against heavy‐metal intoxication includes an efflux system. SilE, a periplasmic silver‐binding protein that is involved in this defense mechanism, has been shown to possess numerous histidine functions, which strongly bind to silver atoms, as demonstrated by ourselves previously. Herein, we address the question of how histidine binds to silver ions as a function of pH value. This property is important because the local proton concentration in cells varies. Thus, we solved the crystal structures of histidine–silver complexes at different pH values and also investigated the influence of the amino‐acid configuration. These results were completed by DFT calculations on the binding strength and packing effects and led to the development of a model for the mode of action of SilE.
Surface‐Assisted Laser Desorption/Ionization Mass Spectrometric Detection of Biomolecules by Using Functional Single‐Walled Carbon Nanohorns as the Matrix
Authors: Ma Rongna , Lu Minghua , Ding Lin , Ju Huangxian , Cai Zongwei
Published: December 2012

A surface‐assisted laser desorption/ionization time‐of‐flight mass spectrometric (SALDI‐TOF MS) method was developed for the analysis of small biomolecules by using functional single‐walled carbon nanohorns (SWNHs) as matrix. The functional SWNHs could transfer energy to the analyte under laser irradiation for accelerating its desorption and ionization, which led to low matrix effect, avoided fragmentation of the analyte, and provided high salt tolerance. Biomolecules including amino acids, peptides, and fatty acids could successfully be analyzed with about 3‐ and 5‐fold higher signals than those obtained using conventional matrix. By integrating the advantages of SWNHs and the recognition ability of aptamers, a selective approach was proposed for simultaneous capture, enrichment, ionization, and MS detection of adenosine triphosphate (ATP). This method showed a greatly improved detection limit (1.0 μM) for the analysis of ATP in complex biological samples. This newly designed protocol not only opened a new application of SWNHs, but also offered a new technique for selective MS analysis of biomolecules based on aptamer recognition systems.
One‐Pot Sequential Organocatalysis: Highly Stereoselective Synthesis of Trisubstituted Cyclohexanols
Authors: Dai Qipu , Arman Hadi , Zhao John Cong‐Gui
Published: December 2012

A highly diastereoselective (d.r. >99:1) and enantioselective (ee value up to 96 %) synthesis of trisubstituted cyclohexanols was achieved by using a one‐pot sequential organocatalysis that involved a quinidine thiourea‐catalyzed tandem Henry–Michael reaction between nitromethane and 7‐oxo‐hept‐5‐en‐1‐als followed by a tetramethyl guanidine (TMG)‐catalyzed tandem retro‐Henry–Henry reaction on the reaction products of the tandem Henry–Michael reaction. Through a mechanistic study, it has also been demonstrated that similar results may also be achieved with this one‐pot sequential organocatalysis by using the racemic Henry product as the substrate.
Fast Track API Manufacturing from Shake Flask to Production Scale Using a 1000‐L Single‐Use Facility
Authors: Minow Benjamin , de Witt Hugo , Knabben Ingo
Published: December 2012

A systematic and integrated use of single‐use technologies was combined with a robust monoclonal antibody platform, which led to a substantial reduction of manufacturing costs, reduced timelines and increased flexibility in clinical manufacturing. A direct scale‐up of a high titer monoclonal antibody‐expressing CHO DG44‐based cell culture platform was performed from shake flasks to a 1000 L production scale in a completely single‐use manufacturing facility. The scale‐up was done on the basis of calculating the specific volumetric power input which allowed a direct transfer from small culture volumes to the production scale. The timelines for process development were reduced to 3 months from the Research Cell Bank to the drug substance with highly optimized cells and appropriate culture conditions.
Single‐Use Technologies for Biopharmaceutical Production: Report from the Working Group Bioprocess Technology – Upstream Processing
Authors: Meusel Wolfram , Kauling Jörg , Löffelholz Christian
Published: December 2012

The main goal of the Bioprocess Technology working group is to overcome existing knowledge deficits in the bioprocess characterization of single‐use bioreactors. The required methods have been investigated extensively, evaluated for their suitability for certain single‐use bioreactors, and summarized into a basic structure in the so‐called conceptual matrix. Development of standard operating procedures for the methods selected as well as their verification in interlaboratory tests guarantee that in the future a spectrum of unified and validated methods can be used to compare different bioreactor types objectively.
The Impact of Geology of Recharge Areas on Groundwater Quality: A Case Study of Zhob River Basin, Pakistan
Authors: Umar Muhammad , Waseem Amir , Sabir Muhammad Amjad , Kassi Akhtar Muhammad , Khan Abdul Salam
Published: December 2012

Groundwater is a major source of water supply for domestic and irrigation uses in semiarid, remote but rapidly developing Kilasaifullah district part of Zhob River Basin, located at Pakistan–Afghanistan Border. Zhob River is among few major rivers of perennial nature in Balochistan, which flows from WSW to ENE and falls in Gomal River, a tributary of Indus River. Keeping in view the important geopolitical position and rapid development of the region, this study is primarily focused on groundwater chemistry for contamination sources as well as agriculture development. Water samples from open and tube wells are analyzed and calculated for electrical conductivity (EC), total dissolved solids (TDS), turbidity, pH, K+, Na+, Ca2+, Mg2+, HCO, Cl−, NO, SO, PO, sodium percent (Na%), sodium adsorption ratio (SAR), Kelly's index (KI), and heavy metals (Fe, Cu, Cr, Zn, Pb, and Mn). On the basis of the chemical constituents two zones within the study area are identified and possible causes of the contaminants are pointed out. Two recharge areas were responsible for the different chemical results in groundwater, e.g., zone A was recharged from NNW saline geological formations (Nisai, Khojak, Multana, Bostan formations, and Muslim Bagh ophiolites), which are concentrated with high sodium and chloride. On the other hand Zone B was sourced from SSW from carbonate rich rocks (Alozai, Loralai, Parh formations, and Muslim Bagh ophiolites). The groundwater is classified as C2–S1, C3–S1, C3–S2, C4–S2 on the basis of EC and SAR values which indicate that most of the water of both zones can be used for irrigation safely except the samples plotted in C3–S2 and C4–S2 categories which could be dangerous for soil and crops. Groundwater samples are plotted in good to permissible limits with some samples excellent to good and few samples belong to doubtful category based on sodium percent. Groundwater of zone A is unsuitable for irrigation use due to higher values of KI (more than one) but water of zone B are good for irrigation based on KI. In general, water of both zones is suitable for irrigation but care should be taken during the selection of crops which are sensitive to alkalinity or sodium hazards particularly in zone A.
Effect of Ozone and Ozone/Fenton in the Advanced Oxidation Process on Biodegradable Characteristics of Semi‐aerobic Stabilized Leachate
Authors: Amr Salem S. Abu , Aziz Hamidi Abdul , Adlan Mohd Nordin , Aziz Shuokr Qarani
Published: December 2012

This study investigated the effects of O3 and O3/H2O2/Fe2+ in the advanced oxidation processes (AOPs) on the biodegradable and soluble characteristics of semi‐aerobic stabilized solid waste leachate. The biodegradability (BOD5/chemical oxygen demand, COD) ratio improved from 0.034 to 0.05 and 0.1 following O3 and O3/H2O2/Fe2+, respectively. Fractions of biodegradable COD(bi) (24%), non‐biodegradable COD(ubi) (76%), soluble COD(s) (59%), biodegradable soluble COD(bsi) (38%), non‐biodegradable soluble COD(ubsi) (62%), and particulate COD (PCOD) (41%) in stabilized leachate were also investigated. The fraction of COD(bi) increased to 28 and 36% after applying O3 and O3/AOPs, respectively. COD(S) increased to 59% after O3 and to 72% after O3/AOPs, whereas COD(bsi) increased to 38 and 51% after O3 and O3/AOPs, respectively. The removal efficiency of COD(S) was obtained at 5% after O3 alone and improved to 51% following ozone‐based AOPs, whereas the removal efficiency of PCOD improved from 25% after O3 to 71% after ozone‐based AOPs.
Effect of Runoff Dynamic on Sediment and Nitrogen Losses in an Agricultural Watershed of the Southern Shaanxi Region, China
Authors: Liu Quan , Li Zhanbin , Li Peng
Published: December 2012

The southern Shaanxi region will become a water source area of the middle route of the South‐to‐North Water Diversion Project after 2014. However, there is little knowledge of water quality conditions in the region. Therefore, 12 rainfall events were monitored to investigate the effect of runoff dynamics on sediment and nitrogen (N) losses during the 2011 rainy season in the Hougou agricultural watershed. The results showed that at the seedling stage (SS), most of the rainfall contributed to an increase in the soil water content, both runoff and sediment yield were small, and there was a significant linear correlation between runoff and sediment yield (r = 0.957, p < 0.01). Despite an increase in vegetation coverage at the vigorous stage (VS), both runoff and sediment yield clearly increased with increasing rainfall, and there was a significant power function relationship between runoff and sediment yield (r = 0.922, p < 0.01). In addition, there was a significant linear correlation between runoff and sediment yield (r = 0.981, p < 0.01) at the harvest stage (HS). The best fit equations among N losses (N) and runoff (R), sediment yield (S) is N = aRbSc, and the method proposed was available to reduce relative error for calculation of N losses during the 2011 rainy season.
Prisoner's dilemma game on adaptive networks under limited foresight
Authors: Xie Fengjie , Cui Wentian , Lin Jun
Published: December 2012

We study the emergence of cooperation in an environment where players in prisoner's dilemma game (PDG) not only update their strategies but also change their interaction relations. Different from previous studies in which players update their strategies according to the imitation rule, in this article, the strategies are updated with limited foresight. We find that two absorbing states—full cooperation and full defection—can be reached, assuming that players can delete interaction relations unilaterally, but new relations can only be created with the mutual consent of both partners. Simulation experiments show that high levels of cooperation in large populations can be achieved when the temptation to defect in PDG is low. Moreover, we explore the factors which influence the level of cooperation. These results provide new insights into the cooperation in social dilemma and into corresponding control strategies. © 2012Wiley Periodicals, Inc. Complexity, 2012
Statistical classification of multivariate flow cytometry data analyzed by manual gating: Stem, progenitor, and epithelial marker expression in nonsmall cell lung cancer and normal lung
Authors: Normolle Daniel P. , Donnenberg Vera S. , Donnenberg Albert D.
Published: December 2012

The use of supervised classification to extract markers from primary flow cytometry data is an emerging field that has made significant progress, spurred by the growing complexity of multidimensional flow cytometry. Whether the markers are extracted without supervision or by conventional gate and region methods, the number of candidate variables identified is typically larger than the number of specimens (p > n) and many variables are highly intercorrelated. Thus, comparison across groups or treatments to determine which markers are significant is challenging. Here, we utilized a data set in which 86 variables were created by conventional manual analysis of individual listmode data files, and compared the application of five multivariate classification methods to discern subtle differences between the stem/progenitor content of 35 nonsmall cell lung cancer and adjacent normal lung specimens. The methods compared include elastic‐net, lasso, random forest, diagonal linear discriminant analysis, and best single variable (best‐1). We described a broadly applicable methodology consisting of: 1) variable transformation and standardization; 2) visualization and assessment of correlation between variables; 3) selection of significant variables and modeling; and 4) characterization of the quality and stability of the model. The analysis yielded both validating results (tumors are aneuploid and have higher light scatter properties than normal lung), as well as leads that require followup: Cytokeratin+ CD133+ progenitors are present in normal lung but reduced in lung cancer; diploid (or pseudo‐diploid) CD117+CD44+ cells are more prevalent in tumor. We anticipate that the methods described here will be broadly applicable to a variety of multidimensional cytometry problems. © 2012 International Society for Advancement of Cytometry
Zweischalige Außenwände: Kommentar zur DIN 18195 Beiblatt 1
Authors: Altaha Nasser
Published: December 2012

Der Beitrag befasst sich mit den in DIN 18195 Beiblatt 1, März 2011, dargestellten Wandskizzen zur Sockelabdichtung von zweischaligem Verblendmauerwerk. Die Anforderungen zur “Entwässerung“ von zweischaligem Mauerwerk sowohl in DIN 18195 Teil 4 und Teil 9 als auch in DIN 18195 Beiblatt 1 basieren ausschließlich auf den Bestimmungen in der Mauerwerksnorm DIN 1053‐1. Die Anforderungen in DIN 1053‐1 zur “Entwässerung“ von zweischaligem Verblendmauerwerk entsprechen jedoch nicht dem bewährten Prinzip dieser Bauweise und wurden daher nicht in die neue deutsche Mauerwerksnorm DIN EN 1996‐2/NA übernommen. Vor diesem Hintergrund bedürfen die zum Thema “Entwässerung“ formulierten Anforderungen in den Abdichtungsnormen DIN 18195‐4, DIN 18195‐9 und DIN 18195 Beiblatt 1 ebenfalls einer Korrektur und Anpassung an den aktuellen Stand der Technik.

Double faced brickwork (cavity brick construction): Comment on the DIN 18195 Supplement 1. The article deals with wall drawings for socket proofing of double facing brickwork that are illustrated in the DIN 18195 Supplement 1, March 2011. The requirements for the “drainage” of double‐wall masonry written down in the DIN 18195 part 4 and part 9 as well as in the supplement 1 to the DIN 18195 are based on the regulations from the masonry standard DIN 1053‐1. The requirements for “dewatering“ of two shells brickwork in the DIN 1053‐1 do not correspond to the proven principle of this building method and are therefore no longer available in the new German masonry standard DIN EN 1996‐2/NA. Against this background, the requirements on “dewatering“ expressed in the DIN 18195‐4, DIN 18195‐9 and DIN 18195 Supplement 1 also need to be corrected and adapted to the current state of the art.
Androgen receptor expression in satellite cells of the neonatal levator ani of the rat
Authors: Swift‐Gallant Ashlyn , Monks D. Ashley
Published: December 2012

Androgens are thought to mediate sexual differentiation of spinal nucleus of the bulbocavernosus (SNB) motoneurons via actions on androgen receptors (ARs) within their target muscles bulbocavernosus and levator ani (LA). However, the cells within these muscles which mediate masculinization of the SNB remain undefined. Until recently, myocytes were thought to be the most likely candidate cell type. However, genetic tests of AR function in myocytes have failed to support a sufficient role for these cells in producing masculine SNB morphology, suggesting the involvement of other cell types. To identify other candidate cell types in the LA, we evaluated whether satellite cells or fibroblasts express AR. Fluorescent immunohistochemistry and confocal microscopy were used to evaluate whether satellite cells and fibroblasts express AR in neonatal male and female rats in the LA and an adjacent sexually monomorphic control muscle (CM). We found that a small proportion of satellite cells in the LA express AR and that this proportion is significantly greater in the LA compared to the CM. No sex differences were found between the proportions of satellite cells expressing AR in either muscle. Less colocalization of satellite cells and AR was seen in postnatal day 3 muscle than in postnatal day 1 muscle. In contrast, only negligible amounts of fibroblasts labeled with S100A4 express AR in either the LA or the CM. Together, findings support satellite cells, but not fibroblasts, as a candidate cell type involved in the sexual differentiation of the SNB neuromuscular system. © 2012 Wiley Periodicals, Inc. Develop Neurobiol 73: 448–454, 2013.
Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8+ memory T cells
Authors: Tartz Susanne , Deschermeier Christina , Retzlaff Silke , Heussler Volker , Sebo Peter , Fleischer Bernhard , Jacobs Thomas
Published: December 2012

Protection against malaria can be achieved by induction of a strong CD8+ T‐cell response against the Plasmodium circumsporozoite protein (CSP), but most subunit vaccines suffer from insufficient memory responses. In the present study, we analyzed the impact of postimmunization sporozoite challenge on the development of long‐lasting immunity. BALB/c mice were immunized by a heterologous prime/boost regimen against Plasmodium berghei CSP that induces a strong CD8+ T‐cell response and sterile protection, which is short‐lived. Here, we show that protective immunity is prolonged by a sporozoite challenge after immunization. Repeated challenges induced sporozoite‐specific antibodies that showed protective capacity. The numbers of CSP‐specific CD8+ T cells were not substantially enhanced by sporozoite infections; however, CSP‐specific memory CD8+ T cells of challenged mice displayed a higher cytotoxic activity than memory T cells of immunized‐only mice. CD4+ T cells contributed to protection as well; but CD8+ memory T cells were found to be the central mediator of sterile protection. Based on these data, we suggest that prolonged protective immunity observed after immunization and infection is composed of different antiparasitic mechanisms including CD8+ effector‐memory T cells with increased cytotoxic activity as well as CD4+ memory T cells and neutralizing antibodies.
Impact of preexisting memory to seasonal A/H1N1 influenza virus on the immune response following vaccination against avian A/H5N1 virus
Authors: Buricchi Francesca , Bardelli Monia , Malzone Carmine , Capecchi Barbara , Nicolay Uwe , Fragapane Elena , Castellino Flora , Del Giudice Giuseppe , Galli Grazia , Finco Oretta
Published: December 2012

Cross‐protection against divergent strains of influenza virus is an objective of various vaccination approaches. B cells cross‐neutralizing several influenza A heterosubtypes have been isolated from cultured human memory B cells (MBCs) and plasmablasts early after influenza vaccination or infection. However, a systematic assessment of the frequency of MBCs and plasmablasts in the blood of healthy individuals is lacking. Here, we show that under resting conditions about 45% of human adults never vaccinated nor exposed to avian A/H5N1 influenza have detectable circulating MBCs cross‐reacting with H5N1. This proportion rises to 63.3% among subjects with a large pool of MBCs specific for seasonal H1N1 (i.e. frequency ≥1% of total IgG MBCs). Moreover, subjects with high baseline frequencies of H1N1‐specific MBCs had an expansion of H5N1‐specific MBCs producing H5‐neutralizing antibodies already after the first dose of an MF59‐adjuvanted H5N1 vaccine. These results suggest that H1N1‐specific MBCs contain a subset of cells cross‐reacting to H5. We propose that a proportion of human adults have a pool of H5/H1 cross‐reactive MBCs that contribute to the rapid rise of the antibody response to divergent influenza strains. This may have implications on vaccination strategies aimed at counteracting future influenza pandemics.
E‐cadherin: From epithelial glue to immunological regulator
Authors: Van den Bossche Jan , Van Ginderachter Jo A.
Published: December 2012

E‐cadherin is best known as a central molecule in adherens junctions, joining adjacent epithelial cells together, thereby safeguarding epithelial barrier function. However, recent findings have uncovered an immunological role for this adhesion molecule, linked to its expression in dendritic cells (DCs) and alternatively activated macrophages (MPHs) and its impact on intracellular signaling pathways. In this respect, E‐cadherin has been shown to influence the immunogenicity/tolerogenicity of DCs through the regulation of β‐catenin functionality. For Langerhans cells (LCs), the DC type found in the skin epidermis, E‐cadherin is known to mediate interactions with keratinocytes (KCs), thereby immobilizing immature LCs in the epidermis and preventing their maturation. In this issue of the European Journal of Immunology, a study by Mayumi et al. [Eur. J. Immunol. 2013. 43: 270–280] now describes a role for E‐cadherin in the final steps of LC differentiation from human peripheral blood monocytes. Although TGF‐β induces LC‐like cells, these intermediates still express the dermal DC marker DC‐SIGN along with Langerin; E‐cadherin ligation is sufficient to induce the full LC phenotype in these cells. Here, we place these findings in the context of current knowledge and propose new avenues for future research.
Synthesis and Characterization of a Soluble Vanadium‐Containing Keggin Polyoxoniobate by ESI‐MS and 51V NMR: (TMA)9[V3Nb12O42]·18H2O
Authors: Son Jung‐Ho , Ohlin C. André , Larson Emma C. , Yu Ping , Casey William H.
Published: December 2012

The vanadium‐containing heteropolyoxoniobate (TMA)9[V3Nb12O42]·18H2O was synthesised by hydrothermal reaction of V2O5 and hydrous niobium oxide in tetramethylammonium hydroxide solution. The cluster has an α‐Keggin structure with a central VO4 and two trans‐bicapped VO5. The water‐soluble product was characterised by X‐ray crystallography, ESI‐MS and both liquid‐ and solid‐state 51V NMR spectroscopy. The solid‐ and solution‐phase 51V NMR spectra indicate two major peaks corresponding to one VO4 and two VO5 sites.
Polyoxometalates as Versatile Enzyme Inhibitors
Authors: Stephan Holger , Kubeil Manja , Emmerling Franziska , Müller Christa E.
Published: December 2012

Polyoxometalates (POMs) are inorganic cluster compounds that have been shown to possess a number of pharmacological properties, including antidiabetic, antibacterial, antiprotozoal, antiviral and anticancer activities. Their molecular mechanism of action is largely unknown. However, several studies indicate that many of their activities may be due to the inhibition of enzymes, in particular, of those enzymes that are accessible from the extracellular space and do not require the penetration of cell membranes. In this review, we describe the recent progress in the preparation and optimization of POMs, and an evaluation of their use as inhibitors of different families of enzymes. The next important steps in this area of research will be to gain a better understanding of the interactions of POMs with enzymes on a structural level through an X‐ray crystallographic study of enzyme–POM complexes and the analysis of structure–activity relationships. Furthermore, POMs with increased stability and in vivo half‐lives have to be prepared. Surface modification may allow the targeting of POM drugs at their sites of action.
BF2OBn·OEt2: A Lewis Acid, Its Use in a Regio‐ and Stereoselective Opening of Trisubstituted Epoxides, and Its Application towards Amphidinolide C and F
Authors: Morra Nicholas A. , Pagenkopf Brian L.
Published: December 2012

The generation of a new Lewis acid (BF2OBn·OEt2) has been reported, and its usefulness has been demonstrated in the regio‐ and stereoselective ring‐opening of trisubstituted epoxides. This Lewis acid is one in a series of new Lewis acids generated from BF3·OEt2 that display varying levels of Lewis acidity. When paired with a modified Shi epoxidation protocol, highly functionalized propionate units, such as those found in a wide variety of natural products, can be accessed. In conjunction with a Mukaiyama oxidative cyclization employing our second generation catalyst Co(nmp)2, this procedure ultimately culminated in the shortest and highest yielding route towards the methyl‐substituted trans‐tetrahydrofuran (trans‐THF) fragment present in amphidinolide C, C2, and F.
Doing it Twice: Asymmetric Deprotonation/Alkylation of Weiss Diketone Derivatives as Key Steps in the Functionalization of Bicyclo[3.3.0]octanes
Authors: Lutz Vanessa , Park Natja , Rothe Christian , Krüger Claudia , Baro Angelika , Laschat Sabine
Published: December 2012

The silyl‐protected allylhydropentalenone derivative 9, derived from the Weiss diketone, was functionalized by enantioselective deprotonation in the presence of lithium bis(1‐phenylethyl)amide/LiCl as the chiral base, which was generated in situ from bis(1‐phenylethyl)ammonium chloride [(R,R)‐ or (S,S)‐14] and BuLi, and trapping of the resulting enolate with alkyl halide electrophiles to give pseudo‐C2 or ‐Cs‐symmetrical bicyclo[3.3.0]octanones 10 and 11. The influence of the chiral base and electrophiles on the regioselectivity and double stereodifferentiation was investigated. Taking the double stereocontrol into account, a matched selectivity for the pseudo‐C2 pair (1R,4R)‐10/(1S,4R)‐10 and a mismatched selectivity for the pseudo‐Cs pair (1S,6R)‐11/(1R,6R)‐11 were observed in the presence of (R,R)‐14. The use of (S,S)‐14, however, produced a mismatched selectivity for (1R,4R)‐10/(1S,4R)‐10 and a matched selectivity for (1S,6R)‐11/(1R,6R)‐11 with complementary diastereoselectivity depending on the electrophile. Furthermore, the hydropentalenone derivative 10a provided an alternative route to the bicyclo[3.3.0]octene core of the macrocyclic tetramic acid lactam, cylindramide (5).
A Six‐year Prospective Study on Children of Mothers with Eating Disorders: The Role of Paternal Psychological Profiles
Authors: Cimino Silvia , Cerniglia Luca , Paciello Marinella , Sinesi Stefania
Published: December 2012

Background

Several studies have suggested that maternal eating disorders (EDs) represent a significant risk factor for children's affective and behavioral development. Yet, little emphasis has been placed on the paternal role.

Objectives

The present longitudinal study aimed to clarify the role of maternal EDs and the influence of paternal psychological profiles on children's emotional development.

Method

Our sample was composed of N = 64 families with firstborn children selected through preschools, primary schools, and outpatient clinics in central Italy. Parents and children participated in a 6‐year longitudinal protocol that included a diagnostic interview conducted by clinicians (Structured Clinical Interview for DSM‐IV Axis I Disorders [SCID‐I]), a self‐report (Symptom Checklist‐90‐Revised [SCL‐90‐R]), and a parental report‐form questionnaire (Child Behavior Checklist [CBCL]).

Results

The influence of mothers’ EDs on their children's emotional development was confirmed. Moreover, fathers’ anxiety and obsessive‐compulsive problems in association with mothers’ EDs and depressive symptoms influenced the onset of both internalizing and externalizing difficulties in their children over time.

Conclusion

Our results suggest that fathers’ psychopathological risk affects the development of emotional problems in children with mothers who have EDs. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.
Synthesis and Photophysical Properties of New Highly Conjugated Bispyrylium Compounds
Authors: Gong Wei‐Tao , Qian Xiao‐min , Wang Fu‐Rui , Lin Yuan , Ning Gui‐Ling
Published: December 2012

New highly conjugated bispyryliums were synthesized by the Knoevenagel reaction between α‐CH3 pyrylium and aromatic dicarboxaldehydes. Their photophysical properties were fully investigated. The results showed that they exhibited a tunable fluorescence emission colors ranging from green to red in solution by changing the properties of connecting π bridges. The experimental results were also supported by theoretical calculations. In addition, their fluorescence emission in solid state was also investigated preliminarily. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 24:66–71, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21064
IS THERE A MEDICAID PENALTY? THE EFFECT OF HOSPITALS' MEDICAID POPULATION ON THEIR PRIVATE PAYER MARKET SHARE
Authors: Sfekas Andrew
Published: December 2012

This study examines whether privately insured patients avoid hospitals with large Medicaid populations. I use a conditional logit model of hospital choice to determine whether the size of a hospital's Medicaid population affects the probability that a privately insured patient will choose that hospital. I focus on the metropolitan area of Tampa, Florida, in the years 1994–1996. I control for hospital fixed effects, hospital‐specific time trends, patients' driving time to the hospital, and interactions between patient and hospital characteristics. I also instrument for the Medicaid population using the predicted Medicaid population. The results show that privately insured patients are less likely to choose a hospital if it served a larger number of Medicaid patients who were admitted through the emergency department in the previous 6 months. The effect persists over time—an additional 6‐month lag cuts the effect in half. Capacity constraints do not seem to be the reason for the effect. I show that the Medicaid effect size could have a moderate effect on the profits of some hospitals. Although limited in scope, this study suggests that hospitals may experience a negative effect on their private revenues when they admit a large population of Medicaid patients. Copyright © 2012 John Wiley & Sons, Ltd.
Eosinophils mediate the pathogenesis of halothane-induced liver injury in mice
Authors: Proctor William R. , Chakraborty Mala , Chea Lynette S. , Morrison Jeffrey C. , Berkson Julia D. , Semple Kenrick , Bourdi Mohammed , Pohl Lance R.
Published: December 2012

Drug-induced liver injury (DILI) is a major health issue, as it remains difficult to predict which new drugs will cause injury and who will be susceptible to this disease. This is due in part to the lack of animal models and knowledge of susceptibility factors that predispose individuals to DILI. In this regard, liver eosinophilia has often been associated with DILI, although its role remains unclear. We decided to investigate this problem in a murine model of halothane-induced liver injury (HILI). When female Balb/cJ mice were administered halothane, eosinophils were detected by flow cytometry in the liver within 12 hours and increased thereafter proportionally to liver damage. Chemokines, eotaxin-1 (CCL11) and eotaxin-2 (CCL24), which are known to attract eosinophils, increased in response to halothane treatment. The severity of HILI was decreased significantly when the study was repeated in wildtype mice made deficient in eosinophils with a depleting antibody and in eosinophil lineage-ablated ΔdblGata−/− mice. Moreover, depletion of neutrophils by pretreating animals with Gr-1 antibody prior to halothane administration failed to reduce the severity of HILI at antibody concentrations that did not affect hepatic eosinophils. Immunohistochemical staining for the granule protein, major basic protein, revealed that eosinophils accumulated exclusively around areas of hepatocellular necrosis.

Conclusion :

Our findings indicate that eosinophils have a pathologic role in HILI in mice and suggest that they may contribute similarly in many clinical cases of DILI.
Intravenous genetic mesothelin vaccine based on human adenovirus 40 inhibits growth and metastasis of pancreatic cancer
Authors: Yamasaki Satoshi , Miura Yoshiaki , Davydova Julia , Vickers Selwyn M. , Yamamoto Masato
Published: December 2012

High pancreatic cancer mortality and poor prognosis are caused by the difficulty for early diagnosis and extremely low rates of resection because of metastasis. Mesothelin overexpression in pancreatic cancer is a remarkable biomarker for tumor progression, especially for invasion and metastasis. Here, we generated a novel replication‐defective recombinant adenovirus 40 (rAd40), whose gene delivery properties are totally different from a conventional rAd5. In this study, we have identified intravenous administration with rAd40 expressing mouse mesothelin (Msln) as an effective prophylactic cancer vaccine against metastatic lesions of pancreatic cancer in mice. Intravenous administration of rAd40 (rAd40 i.v.) achieved transgene delivery in wider range of organs compared to rAd5 i.v., while rAd5 was distributed mainly to the liver, spleen, and lungs. Additionally, rAd40 i.v. showed less transduction of the liver or inflammatory responses, resulted in reduced liver toxicity compared to rAd5 i.v. Also, more robust systemic antigen‐specific immune responses were stimulated by rAd40 i.v. Pretreatment with a single ovalbumin‐expressing rAd40 i.v. prevented tumor growth in mouse subcutaneous models of ovalbumin‐expressing pancreatic cancer. When used with Msln‐expressing rAd40 i.v., Msln protein expression and metastases were suppressed in a syngeneic orthotopic mouse model of pancreatic cancer, corresponding to the detection of Msln‐ and tumor‐specific cytotoxic T lymphocyte (CTL). Our novel methods generated antitumor effects against antigen‐expressing tumors through antigen‐ and tumor‐specific CTL‐mediated immunity. Thus, our results indicate that a rAd40‐based intravenous vaccine provides a new strategy for the effective control of metastatic pancreatic cancer and novel therapy against other cancers and infectious diseases.
Prospective follow‐up of 2,065 young unscreened women to study human papillomavirus incidence and clearance
Authors: Schmeink C.E. , Massuger L.F.A.G. , Lenselink C.H. , Quint W.G.V. , Witte B.I. , Berkhof J. , Melchers W.J.G. , Bekkers R.L.M.
Published: December 2012

Human papillomavirus (HPV) is a necessary factor in the development of cervical intraepithelial neoplasia and cervical cancer. However, HPV is also a very common sexually transmitted virus and many women clear their infection. To study HPV incidence and clearance, 2,065 women, aged 18–29 years, were followed for 12 months and were asked to provide a self‐collected cervico‐vaginal sample and fill‐out a questionnaire every 3 months. For HPV DNA detection, the SPF10‐DEIA LiPA25 system was used. Incidence rates of any‐type high‐risk HPV and low‐risk HPV were 17.0 per 1,000‐person months, and 14.3 per 1,000‐person months, respectively. HPV types 16, 52, 51 and 31 had the highest type‐specific incidence rates. HPV incidence was increased in singles, and women having a new relationship. A higher number of lifetime sex partners, and a higher frequency of sexual contacts in the past 3 months was associated with an increased HPV incidence. The overall clearance of the newly detected type‐specific high‐risk HPV infections and low‐risk HPV infections was 61.2% and 69.0%, respectively. Having a sexual relationship compared to being single, and a higher sexual age both positively influenced the clearance of any‐type high‐risk HPV. Among the women infected with HPV 16, the women who had a co‐infection had a lower proportion of clearance of HPV 16. In conclusion, in this young Dutch study population, HPV incidence rates are not related to age and comparable to other western countries. Clearance was only independently related to factors associated with sexual behavior, either past or current.
KRAS and BRAF mutation status in circulating colorectal tumor cells and their correlation with primary and metastatic tumor tissue
Authors: Mostert Bianca , Jiang Yuqiu , Sieuwerts Anieta M. , Wang Haiying , Bolt‐de Vries Joan , Biermann Katharina , Kraan Jaco , Lalmahomed Zarina , van Galen Anne , de Weerd Vanja , van der Spoel Petra , Ramírez‐Moreno Raquel , Verhoef Cornelis , IJzermans Jan N.M. , Wang Yixin , Gratama Jan‐Willem , Foekens John A. , Sleijfer Stefan , Martens John W.M.
Published: December 2012

Although anti‐EGFR therapy has established efficacy in metastatic colorectal cancer, only 10‐20% of unselected patients respond. This is partly due to KRAS and BRAF mutations, which are currently assessed in the primary tumor. To improve patient selection, assessing mutation status in circulating tumor cells (CTCs), which possibly better represent metastases than the primary tumor, could be advantageous. We investigated the feasibility of KRAS and BRAF mutation detection in colorectal CTCs by comparing three sensitive methods and compared mutation status in matching primary tumor, liver metastasis and CTCs. CTCs were isolated from blood drawn from 49 patients before liver resection using CellSearch™. DNA and RNA was isolated from primary tumors, metastases and CTCs. Mutations were assessed by co‐amplification at lower denaturation temperature‐PCR (Transgenomic™), real‐time PCR (EntroGen™) and nested Allele‐Specific Blocker (ASB‐)PCR and confirmed by Sanger sequencing. In 43 of the 49 patients, tissue RNA and DNA was of sufficient quantity and quality. In these 43 patients, discordance between primary and metastatic tumor was 23% for KRAS and 7% for BRAF mutations. RNA and DNA from CTCs was available from 42 of the 43 patients, in which ASB‐PCR was able to detect the most mutations. Inconclusive results in patients with low CTC counts limited the interpretation of discrepancies between tissue and CTCs. Determination of KRAS and BRAF mutations in CTCs is challenging but feasible. Of the tested methods, nested ASB‐PCR, enabling detection of KRAS and BRAF mutations in patients with as little as two CTCs, seems to be superior.
Site‐specific survival rates for cancer of unknown primary according to location of metastases
Authors: Hemminki Kari , Riihimäki Matias , Sundquist Kristina , Hemminki Akseli
Published: December 2012

Cancer of unknown primary (CUP) is diagnosed at the metastatic stage and despite extensive diagnostic work‐up the primary tumor often remains unidentified. Limited population‐based survival data are available for metastatic location and none are available that link the location with the cause of death, which might give clues about the tissue‐of‐origin. A total of 9,306 CUP patients with extranodal metastases of adenocarcinoma and undifferentiated histology were identified from the Swedish Cancer Registry. Hazard ratios (HRs), mean survival times and Kaplan–Meier survival curves were provided according to CUP location at diagnosis and cause of death. The median survival was shortest (2 months) for patients with liver and longest (5 months) for those with nervous system metastases. Lung cancer was the most common cause of death in patients with CUP metastasis in the respiratory system, nervous system, bone and skin, with a median survival of 3 months. Patients with peritoneal/retroperitoneal and pelvical metastasis died not only of ovarian cancer, with a favorable median survival of 8 months, but also of pancreatic and colorectal cancers. Patients with pancreatic, liver, biliary and colorectal cancers with liver metastasis succumbed quickly. The data show that the location of metastases predicts site‐specific cancer deaths which in turn may point to the hidden primary tumor. The results should facilitate the management of CUP in proposing that the diagnostic arsenal should target the lungs when metastases are diagnosed in the respiratory or nervous system, bone or skin; ovarian tumors should be suspected after diagnosis of pelvical metastases.
A Present Understanding of Colloidal Quantum Dot Blinking
Authors: Schwartz Osip , Oron Dan
Published: December 2012

Luminescence intermittency, also termed ‘blinking’, refers to spontaneous changes in the brightness of a luminescent fluorophore under continuous optical excitation. Blinking was first observed in colloidal semiconductor nanocrystals over fifteen years ago, shortly after synthetic protocols became advanced enough to produce brightly luminescent nanocrystals. The underlying physical mechanism was initially associated with long‐lived photo‐induced charging of the nanocrystals. In recent years, however, significant evidence has accumulated to point at a more complex physical picture of the process, which involves several distinct mechanisms and is mediated by surface charge trapping. In parallel, efforts to synthesize highly luminescent semiconductor nanocrystals that do not exhibit blinking have recently borne fruit. We review the recent progress in understanding of blinking and potential applications in bioimaging using inorganic fluorescent tags.
The Influence of Alloy Composition on the Electronic Properties of IV–VI Core/Shell Colloidal Heterostructures
Authors: Lifshitz Efrat , Vaxenburg Roman , Maikov Georgy I. , Rubin‐Brusilovski Anna , Yanover Diana , Tilchin Jenya , Sashchiuk Aldona
Published: December 2012

Considering the significant potential of IV–VI colloidal nanostructures in various technologies, this review describes the development and characterization of unique IV–VI derivatives, consisting of core/shell heterostructures, when either the core or the shell (or both) has an alloy composition with the chemical formula PbSexS1−x/PbSeyS1−y (0≤x(y)≤1). We describe the synthetic procedures and a thorough investigation of the optical properties of the discussed materials. The experimental evidence is supported by suitable electronic band structure calculations. The special properties are expressed as fine tunability of the electronic properties, chemical and temperature stability, variation of electronphonon interactions, emission Stokes shifts and lifetimes, upon the variation of the composition and/or architecture of the heterostructures. The properties obtained are of significant importance in opto‐electronic applications.