bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, characterization, and performance evaluation of the AM/AMPS/DMDAAC/SSS quadripolymer as a fluid loss additive for water‐based drilling fluid
Authors: Bai Xiaodong , Yang Yi , Xiao Dingyuan , Pu Xiaolin , Wang Xu
Published: December 2014

According to the molecular structure design requirements of the fluid loss additive resistant to high temperature, 2‐acrylamide‐2‐methyl propane sulfonic acid (AMPS), acrylamide (AM), dimethyl diallyl ammonium chloride (DMDAAC) and sodium styrene sulfonate (SSS) are selected as the structure monomers. Using ammonium persulfate as initiator, a new quadripolymer is synthesized through free radical aqueous solution polymerization. According to the minimum filtration loss of the fresh water‐based drilling fluid with 0.5 wt % quadripolymer, The synthesis conditions are optimized by orthogonal test: the mole ratio of AMPS/AM/DMDAAC/SSS is 5/7/2/1, the monomer concentration is 30 wt %, the initiator concentration is 0.8 wt %, the reaction temperature is 75°C and the pH is 10. The structure of the quadripolymer is characterized by Fourier transform infrared spectroscopy and nuclear magnetic resonance hydrogen spectroscopy. The results show that the quadripolymer contains all the designed functional groups. The thermal stability of the quadripolymer is tested by thermogravimetry, differential thermogravimetry, and differential scanning calorimetry. The results show that the thermal degradation of the quadripolymer is not obvious before 272.3°C. The rheological performance and filtration loss of the quadripolymer are evaluated. The results indicate that the filtration loss decreases with the increasing dosage of the quadripolymer before and after thermal aging test at 180°C for 16 h, and the filtration loss before the thermal aging test is smaller than that after the thermal aging test. The high temperature high pressure filtration loss (FL(HTHP)) experiment results also show that the quadripolymer fluid loss additive has excellent temperature‐resistant performance. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41762.
Copper‐Catalyzed Formal CH Carboxylation of Aromatic Compounds with Carbon Dioxide through Arylaluminum Intermediates
Authors: Ueno Atsushi , Takimoto Masanori , O Wylie W. N. , Nishiura Masayoshi , Ikariya Takao , Hou Zhaomin
Published: December 2014

The CH bond carboxylation of various aromatic compounds with CO2 was achieved by the deprotonative alumination with a mixed alkyl amido lithium aluminate compound iBu3Al(TMP)Li followed by the NHC‐copper‐catalyzed carboxylation of the resulting arylaluminum species, which afforded the corresponding carboxylation products in high yield and high selectivity. In addition to benzene derivatives, heteroarenes such as benzofuran, benzothiophene, and indole derivatives are also suitable substrates. Functional groups such as Cl, Br, I, vinyl, amide, and CN could survive the reaction conditions. Some key reaction intermediates such as the copper aryl and isobutyl complexes and their carboxylation products were isolated and structurally characterized by X‐ray crystallographic analyses, thus offering important information on the reaction mechanism.
Exploring the consequences of a representative “disallowed” conformation of Aib on a 310‐helical fold
Authors: Tumminakatti Shama , Reddy Damodara N. , Prabhakaran Erode N.
Published: December 2014

The structural effects of a representative “disallowed” conformation of Aib on the 310‐helical fold of an octapeptidomimetic are explored. The 1D (1H, 13C) & 2D NMR, FT‐IR and CD data reveal that the octapeptide 1, adopts a 310‐helical conformation in solution, as it does in its crystal structure. The C‐terminal methyl carboxylate (CO2Me) of 1 was modified into an 1,3‐oxazine (Oxa) functional group in the peptidomimetic 2. This modification results in the stabilization of the backbone of the C‐terminal Aib (Aib*‐Oxa) of 2, in a conformation (ϕ, ψ = 180, 0) that is natively disallowed to Aib. Consequent to the presence of this natively disallowed conformation, the 310‐helical fold is not disrupted in the body of the peptidomimetic 2. But the structural distortions that do occur in 2 are primarily in residues in the immediate vicinity of the natively disallowed conformation, rather than in the whole peptide body. Non‐native electronic effects resulting from modifications in backbone functional groups can be at the origin of stabilizing residues in natively disallowed conformations. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 21–36, 2015.
Diarylheptanoids from Green Alder Bark and Their Potential for DNA Protection
Authors: Novaković Miroslav , Stanković Miroslava , Vučković Ivan , Todorović Nina , Trifunović Snežana , Apostolović Danijela , Mandić Boris , Veljić Milan , Marin Petar , Tešević Vele , Vajs Vlatka , Milosavljević Slobodan
Published: December 2014

Nine diarylheptanoids, 1–9, catechin (11), and a phenolic glucoside, 10, were isolated from the bark of green alder (Alnus viridis). Four of the isolated compounds, i.e., 2, 5, 8, 10, are new. The structures of 1–11 were determined on the basis of spectroscopic data. All isolated compounds were evaluated for their in vitro protective effects on chromosome aberrations in peripheral human lymphocytes using cytokinesis‐block micronucleus (CBMN) assay. Almost all of them exerted a pronounced effect of decreasing DNA damage of human lymphocytes, acting stronger than the known synthetic protector amifostine.
Inhibition of CREB Phosphorylation by Conjugates of Adenosine Analogues and Arginine‐Rich Peptides, Inhibitors of PKA Catalytic Subunit
Authors: Kriisa Marie , Sinijärv Hedi , Vaasa Angela , Enkvist Erki , Kostenko Sergiy , Moens Ugo , Uri Asko
Published: December 2014

Bisubstrate inhibitors of protein kinases associate simultaneously with two substrate‐binding sites of the kinase and thus potentially possess better inhibitory potency and selectivity than inhibitors binding to only the conserved ATP‐site of the kinase. We have previously used conjugates of adenosine analogues and arginine‐rich peptides (ARCs) to develop proteolytically stable cell plasma membrane‐permeable bisubstrate inhibitors whose biochemical affinities towards several basophilic protein kinases of the AGC group are in the picomolar range. The potency of bisubstrate inhibitors to affect the phosphorylation of proteins in living cells has been described in a limited number of publications. In this study, the effect of ARCs on the protein kinase A (PKA)‐catalysed cAMP response element‐binding protein (CREB) phosphorylation pathway was studied in living mammalian cells. Our results demonstrate that at low micromolar extracellular concentration N‐myristoylated ARCs are capable of reducing the activity of transcription factor CREB through inhibition of PKA.
Dynamics of the Intrinsically Disordered C‐Terminal Domain of the Nipah Virus Nucleoprotein and Interaction with the X Domain of the Phosphoprotein as Unveiled by NMR Spectroscopy
Authors: Baronti Lorenzo , Erales Jenny , Habchi Johnny , Felli Isabella C. , Pierattelli Roberta , Longhi Sonia
Published: December 2014

We provide an atomic‐resolution description based on NMR spectroscopy, of the intrinsically disordered C‐terminal domain of the Nipah virus nucleoprotein (NTAIL), both in its isolated state and within the nucleocapsid (NC). Within the NC the second half of NTAIL retains conformational behavior similar to that of isolated NTAIL, whereas the first half of NTAIL becomes much more rigid. In spite of the mostly disordered nature of NTAIL, chemical shifts and relaxation measurements show a significant degree of α‐helical sampling in the molecular recognition element (MoRE) involved in binding to the X domain (XD) of the phosphoprotein, with this preconfiguration being more pronounced than in the NTAIL domain from the cognate Hendra virus. Outside the MoRE, an additional region exhibiting reduced flexibility was identified within NTAIL and found to be involved in binding to the XD. 1H‐ and 13C‐detected titration NMR experiments support a highly dynamic binding of NTAIL at the surface of the XD.
Angiotensin‐converting enzyme inhibitors‐induced angioedema treated by C1 esterase inhibitor concentrate (Berinert®): about one case and review of the therapeutic arsenal
Authors: Lipski Samuel Michael , Casimir Georges , Vanlommel Martine , Jeanmaire Mathieu , Dolhen Pierre
Published: December 2014

Key Clinical Message

C1 esterase inhibitor (Berinert®) is generally used to treat severe attack of hereditary angioedema. We describe here the case of a patient who presented with a severe angioedema induced by angiotensin‐converting enzyme inhibitors (ACEIs) endangering her life. It could be successfully treated with that medicine.
A Double Conformationally Restricted Dynamic Supramolecular System for the Substrate‐Selective Epoxidation of Olefins—A Comparative Study on the Influence of Preorganization
Authors: Lindbäck Emil , Cherraben Sawsen , Francoïa Jean‐Patrick , Sheibani Esmaeil , Lukowski Bartosz , Proñ Agnieszka , Norouzi‐Arasi Hassan , Månsson Kristoffer , Bujalowski Pawel , Cederbalk Anna , Pham Thanh Huong , Wixe Torbjörn , Dawaigher Sami , Wärnmark Kenneth
Published: December 2014

A double conformationally restricted kinetically labile supramolecular catalytic system, the third generation, was designed and synthesized. We investigated the substrate selectivity of this system by performing competitive pairwise epoxidations of pyridyl‐ and phenyl‐appended olefins. We compared the obtained substrate selectivities to previous less preorganized generations of this system. Five different substrate pairs were investigated, and the present double conformationally restricted system showed higher normalized substrate selectivities (pyridyl versus phenyl) for two of the substrate pairs than the previous less conformationally restricted generations. As for the preorganization of the components of the system, the catalyst, and the receptor part, it was shown that for each substrate pair there was one generation that was better than the other to generate substrate‐selective catalysis.
Bifunctional One‐Component Catalysts for the Addition of Carbon Dioxide to Epoxides
Authors: Büttner Hendrik , Lau Kornelia , Spannenberg Anke , Werner Thomas
Published: December 2014

Several bifunctional ammonium salts were synthesized and employed as one‐component catalysts for the conversion of CO2 and epoxides to produce cyclic carbonates. These catalysts show superior activities compared to their monofunctional analogs. A turnover number of up to 693 and a turnover frequency of up 392 h−1 could be achieved for the best catalyst. Moreover, the effect of various solvents has been studied. All employed solvents and the product formed had a negative influence on substrate conversion. The scope and limitation of the reaction has been studied carefully for two general reaction protocols at 45 and 90 °C. In over 20 examples, the isolated yields after filtration were 90 %. In addition, we present the first organocatalyzed synthesis of a cyclohexene‐based naturally occurring cyclic carbonate, and its molecular structure was determined by XRD. Furthermore, we demonstrate that the reaction can be performed even on a multigram scale and can be monitored by in situ FTIR spectroscopy.
Selective Aerobic Benzylic Alcohol Oxidation of Lignin Model Compounds: Route to Aryl Ketones
Authors: Dawange Monali , Galkin Maxim V. , Samec Joseph S. M.
Published: December 2014

A mild and chemoselective oxidation of the α‐alcohol in β‐O‐4′‐ethanoaryl and β‐O‐4′‐glycerolaryl ethers has been developed. The benzylic alcohols were selectively dehydrogenated to the corresponding ketones in 60–93 % yield. A one‐pot selective route to aryl ethyl ketones was performed. The catalytic system comprises recyclable heterogeneous palladium, mild reaction conditions, green solvents, and oxygen in air as oxidant. Catalytic amounts of a coordinating polyol were found pivotal for an efficient aerobic oxidation.
Titania Nanoparticles Stabilized HPA in SBA‐15 for the Intermolecular Hydroamination of Activated Olefins
Authors: Sawant‐Dhuri Dhanashri , Balasubramanian Veerappan V. , Ariga Katsuhiko , Park Dae‐Hwan , Choy Jin‐Ho , Cha Wang Soo , Al‐deyab Salem S. , Halligudi Shivappa B. , Vinu Ajayan
Published: December 2014

The front cover artwork for Issue 12/2014 is a collaborative research between India, Japan, Australia, Korea and Saudi Arabia. The image shows the highly selective and active nanoparticle stabilized mesoporous catalytic system for the hydroamination of aromatic and aliphatic amines. See the Full Paper itself on page http://dx.doi.org/10.1002/cctc.201402449.
Spin Frustration in a Family of Pillared Kagomé Layers of High‐Spin Cobalt(II) Ions
Authors: Wang Long‐Fei , Li Cui‐Jin , Chen Yan‐Cong , Zhang Ze‐Min , Liu Jiang , Lin Wei‐Quan , Meng Yan , Li Quan‐Wen , Tong Ming‐Liang
Published: December 2014

Based on the analogous kagomé [Co3(imda)2] layers (imda=imidazole‐4,5‐dicarboxylate), a family of pillar‐layered frameworks with the formula of [Co3(imda)2(L)3]⋅(L)n⋅xH2O (1: L=pyrazine, n=0, x=8; 2: L=4,4′‐bipyridine, n=1, x=8; 3: L=1,4‐di(pyridin‐4‐yl)benzene, n=1, x=13; 4: L=4,4′‐di(pyridin‐4‐yl)‐1,1′‐biphenyl, n=1, x=14) have been successfully synthesized by a hydrothermal/solvothermal method. Single‐crystal structural analysis shows a significant increase in the interlayer distances synchronized with the extension of the pillar ligands, namely, 7.092(3) (1), 10.921(6) (2), 14.780(5) (3), and 19.165(4) Å (4). Despite the wrinkled kagomé layers in complexes 2–4, comprehensive magnetic characterizations revealed weakening of interlayer magnetic interactions and an increase in the degree of frustration as the pillar ligand becomes longer from 1 to 4; this leads to characteristic magnetic ground states. For compound 4, which has the longest interlayer distance, the interlayer interaction is so weak that the magnetic properties observed within the range of temperature measured would correspond to the frustrated layer.
A Bismuth‐Based Metal–Organic Framework as an Efficient Visible‐Light‐Driven Photocatalyst
Authors: Wang Guanzhi , Sun Qilong , Liu Yuanyuan , Huang Baibiao , Dai Ying , Zhang Xiaoyang , Qin Xiaoyan
Published: December 2014

A visible‐light‐responsive bismuth‐based metal–organic framework (Bi‐mna) is demonstrated to show good photoelectric and photocatalytic properties. Combining experimental and theoretical results, a ligand‐to‐ligand charge transfer (LLCT) process is found to be responsible for the high performance, which gives rise to a longer lifetime of photogenerated charge carriers. Our results suggest that bismuth‐based MOFs could be promising candidates for the development of efficient visible‐light photocatalysts.
Hierarchical‐Structured Anatase‐Titania/Cellulose Composite Sheet with High Photocatalytic Performance and Antibacterial Activity
Authors: Luo Yan , Huang Jianguo
Published: December 2014

Bulk hierarchical anatase‐titania/cellulose composite sheets were fabricated by subjecting an ultrathin titania gel film pre‐deposited filter paper to a solvo‐co‐hydrothermal treatment by using titanium butoxide as the precursor to grow anatase‐titania nanocrystallites on the cellulose nanofiber surfaces. The titanium butoxide specie is firstly absorbed onto the nanofibers of the cellulose substance through a solvothermal process, which was thereafter hydrolyzed and crystallized upon the subsequent hydrothermal treatment, leading to the formation of fine anatase‐titania nanoparticles with sizes of 2–5 nm uniformly anchored on the cellulose nanofibers. The resulting anatase‐titania/cellulose composite sheet shows a significant photocatalytic performance towards degradation of a methylene blue dye, and introduction of silver nanoparticles into the composite sheet yields an Ag‐NP/anatase‐titania/cellulose composite material possessing excellent antibacterial activity against both Gram‐positive and Gram‐negative bacteria.
Halogen Bonding Controls the Regioselectivity of the Deiodination of Thyroid Hormones and their Sulfate Analogues
Authors: Manna Debasish , Mondal Santanu , Mugesh Govindasamy
Published: December 2014

The type 1 iodothyronine deiodinase (1D‐1) in liver and kidney converts the L‐thyroxine (T4), a prohormone, by outer‐ring (5′) deiodination to biologically active 3,3′,5‐triiodothyronine (T3) or by inner‐ring (5) deiodination to inactive 3,3′,5′‐triiodothronine (rT3). Sulfate conjugation is an important step in the irreversible inactivation of thyroid hormones. While sulfate conjugation of the phenolic hydroxyl group stimulates the 5‐deiodination of T4 and T3, it blocks the 5′‐deiodination of T4. We show that thyroxine sulfate (T4S) undergoes faster deiodination as compared to the parent thyroid hormone T4 by synthetic selenium compounds. It is also shown that ID‐3 mimics, which are remarkably selective to the inner‐ring deiodination of T4 and T3, changes the selectivity completely when T4S is used as a substrate. From the theoretical investigations, it is observed that the strength of halogen bonding increases upon sulfate conjugation, which leads to a change in the regioselectivity of ID‐3 mimics towards the deiodination of T4S. It has been shown that these mimics perform both the 5′‐ and 5‐ring deiodinations by an identical mechanism.
Synthesis of High‐Mannose Oligosaccharide Analogues through Click Chemistry: True Functional Mimics of Their Natural Counterparts Against Lectins?
Authors: François‐Heude Marc , Méndez‐Ardoy Alejandro , Cendret Virginie , Lafite Pierre , Daniellou Richard , Ortiz Mellet Carmen , García Fernández José M. , Moreau Vincent , Djedaïni‐Pilard Florence
Published: December 2014

Terminal “high‐mannose oligosaccharides” are involved in a broad range of biological and pathological processes, from sperm‐egg fusion to influenza and human immunodeficiency virus infections. In spite of many efforts, their synthesis continues to be very challenging and actually represents a major bottleneck in the field. Whereas multivalent presentation of mannopyranosyl motifs onto a variety of scaffolds has proven to be a successful way to interfere in recognition processes involving high‐mannose oligosaccharides, such constructs fail at reproducing the subtle differences in affinity towards the variety of protein receptors (lectins) and antibodies susceptible to binding to the natural ligands. Here we report a family of functional high‐mannose oligosaccharide mimics that reproduce not only the terminal mannopyranosyl display, but also the core structure and the branching pattern, by replacing some inner mannopyranosyl units with triazole rings. Such molecular design can be implemented by exploiting “click” ligation strategies, resulting in a substantial reduction of synthetic cost. The binding affinities of the new “click” high‐mannose oligosaccharide mimics towards two mannose specific lectins, namely the plant lectin concanavalin A (ConA) and the human macrophage mannose receptor (rhMMR), have been studied by enzyme‐linked lectin assays and found to follow identical trends to those observed for the natural oligosaccharide counterparts. Calorimetric determinations against ConA, and X‐ray structural data support the conclusion that these compounds are not just another family of multivalent mannosides, but real “structural mimics” of the high‐mannose oligosaccharides.
Ru‐Catalyzed Decarboxylative Annulations of α‐Keto Acids with Internal Alkynes: Dual Roles of COOH as Directing Group and Leaving Group
Authors: Tan Hui , Li Hongji , Wang Jiawang , Wang Lei
Published: December 2014

Carboxylic acid serving as both directing and leaving group was discovered in Ru‐catalyzed decarboxylative annulations of α‐keto acids with alkynes. The well‐established protocol showed high functional group tolerance, which provided an efficient and alternative route to the coumarone backbone.
Replacement of Water Molecules in a Phosphate Binding Site by Furanoside‐Appended lin‐Benzoguanine Ligands of tRNA‐Guanine Transglycosylase (TGT)
Authors: Barandun Luzi J. , Ehrmann Frederik R. , Zimmerli Daniel , Immekus Florian , Giroud Maude , Grünenfelder Claudio , Schweizer W. Bernd , Bernet Bruno , Betz Michael , Heine Andreas , Klebe Gerhard , Diederich François
Published: December 2014

The enzyme tRNA‐guanine transglycosylase has been identified as a drug target for the foodborne illness shigellosis. A key challenge in structure‐based design for this enzyme is the filling of the polar ribose‐34 pocket. Herein, we describe a novel series of ligands consisting of furanoside‐appended lin‐benzoguanines. They were designed to replace a conserved water cluster and differ by the functional groups at C(2) and C(3) of the furanosyl moiety being either OH or OMe. The unfavorable desolvation of Asp102 and Asp280, which are located close to the ribose‐34 pocket, had a significant impact on binding affinity. While the enzyme has tRNA as its natural substrate, X‐ray co‐crystal structures revealed that the furanosyl moieties of the ligands are not accommodated in the tRNA ribose‐34 site, but at the location of the adjacent phosphate group. A remarkable similarity of the position of the oxygen atoms in these two structures suggests furanosides as a potential phosphate isoster.
Unprecedented Oxidative Addition and Metal‐Only Lewis Pair Chemistry of Antimony Trihalides
Authors: Braunschweig Holger , Dewhurst Rian D. , Hupp Florian , Wolf Justin
Published: December 2014

Reaction of the zero‐valent platinum complex [Pt(PCy3)2] with SbF3 generates the cationic diplatinum stibenium complex [{(Cy3P)2Pt}2(μ‐SbF2)]+, the first unsupported metal‐only Lewis pair containing an antimony‐centered Lewis acid. In contrast, SbCl3 undergoes oxidative addition to [Pt(PCy3)2], resulting in the dihalostibanyl complex trans‐[PtCl(SbCl2)(PCy3)2], the first example of oxidative addition of an antimony–halide bond to a transition metal.
Brønsted Acid‐Catalyzed, Highly Enantioselective Addition of Enamides to In Situ‐Generated ortho‐Quinone Methides: A Domino Approach to Complex Acetamidotetrahydroxanthenes
Authors: Saha Satyajit , Schneider Christoph
Published: December 2014

The highly enantioselective conjugate addition of enamides and enecarbamates to in situ‐generated ortho‐quinone methides, upon subsequent N,O‐acetalization, gives rise to acetamido‐substituted tetrahydroxanthenes with generally excellent enantio‐ and diastereoselectivities. A chiral BINOL‐based phosphoric acid catalyst controls the enantioselectivity of the carbon–carbon bond‐forming event. The products are readily converted into other xanthene‐based heterocycles.
Combination of Solid‐Phase Micro‐Extraction and Direct Analysis in Real Time‐Fourier Transform Ion Cyclotron Resonance Mass Spectrometry for Sensitive and Rapid Analysis of 15 Phthalate Plasticizers in Beverages
Authors: Wu Mengxi , Wang Haoyang , Dong Guoqing , Musselman Brian D. , Liu Charles C. , Guo Yinlong
Published: December 2014

A method for rapid identification and quantification of phthalate plasticizers in beverages was developed. A number of 15 phthalate plasticizers which covered all the phthalates concerned in the US Consumer Product Safety Improvement Act (CPSIA), European Union legislations and Chinese national standards (GB) were analyzed. By a combined solid‐phase micro‐extraction (SPME) and direct analysis in real time mass spectrometry (DART‐MS) approach, phthalates at sub‐ng·mL−1 levels can be qualitatively and quantitatively analyzed in a short time. The use of ultrahigh‐resolving power and the accurate mass measurement capacity naturally provided by Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR‐MS) minimizes the matrix interferences and thus enables the evaluation of phthalates in a complex matrix without extensive sample handlings or preparations. The limits of quantification (LOQs) were estimated to be at 0.3–5.0 ng·mL−1, lower than the Maximum Residue Limit (MRL) regulated by the European Union legislations (2007/19/EC) in foods, beverages, food packaging and toys (0.3–30 ng·mL−1). This rapid and easy‐to‐use SPME‐DART‐FT‐ICR‐MS method provided a relatively high‐throughput and powerful analytical approach for quick testing and screening phthalates in beverages and water samples to ensure food safety.
Merging Allosteric and Active Site Binding Motifs: De novo Generation of Target Selectivity and Potency via Natural‐Product‐Derived Fragments
Authors: Lanz Jan , Riedl Rainer
Published: December 2014

The de novo design of molecules from scratch with tailored biological activity is still the major intellectual challenge in chemical biology and drug discovery. Herein we validate natural‐product‐derived fragments (NPDFs) as excellent molecular seeds for the targeted de novo discovery of lead structures for the modulation of therapeutically relevant proteins. The application of this de novo approach delivered, in synergy with the combination of allosteric and active site binding motifs, highly selective and ligand‐efficient non‐zinc‐binding (3: 4‐{[5‐(2‐{[(3‐methoxyphenyl)methyl]carbamoyl}eth‐1‐yn‐1‐yl)‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐1‐yl]methyl}benzoic acid) as well as zinc‐binding (4: 4‐({5‐[2‐({[3‐(3‐carboxypropoxy)phenyl]methyl}carbamoyl)eth‐1‐yn‐1‐yl]‐2,4‐dioxo‐1,2,3,4‐tetrahydropyrimidin‐1‐yl}methyl)benzoic acid) uracil‐based MMP‐13 inhibitors presenting IC50 values of 11 nM (3: LE=0.35) and 6 nM (4: LE=0.31).
Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma
Authors: Sherman William H. , Chu Kyung , Chabot John , Allendorf John , Schrope Beth Ann , Hecht Elizabeth , Jin Brian , Leung David , Remotti Helen , Addeo Gisella , Postolov Inna , Tsai Wei , Fine Robert L.
Published: December 2014

BACKGROUND

This prospective study was undertaken to assess toxicity, resectability, and survival in pancreatic adenocarcinoma patients presenting with locally advanced, unresectable disease treated with neoadjuvant gemcitabine, docetaxel, and capecitabine (GTX) and gemcitabine and capecitabine (GX)/radiation therapy (RT).

METHODS

All patients presenting to the Pancreas Center were evaluated for eligibility. Forty‐five patients (mean age, 64 years; range, 44‐83 years)—34 patients deemed unresectable because of arterial involvement and 11 patients deemed unresectable because of extensive venous involvement—were treated with 6 cycles of GTX. Those with arterial involvement were treated with GX/RT after chemotherapy.

RESULTS

The GTX and GX/RT treatments were tolerated with the expected drug‐related toxicities. There were no bowel perforations, cases of pancreatitis, or delayed strictures. Among those with arterial involvement, 29 underwent subsequent resection, with 20 (69%) achieving R0 resections. All 11 patients with venous‐only involvement underwent resection, with 8 achieving R0 resections and 3 achieving complete pathologic responses. For the arterial arm, the 1‐year survival rate was 71% (24 of 34 patients), and the median survival was 29 months (95% confidence interval, 21‐38 months). Thirteen patients (38%) have not relapsed (range, 5‐49+ months). For the venous arm, the median survival has not been reached at more than 42 months. Six patients (55%) in the venous arm did not experience recurrence (range, 6.2‐42+ months).

CONCLUSIONS

GTX plus GX/RT is an effective neoadjuvant regimen that can be safely administered to patients up to at least the age of 83 years. It is associated with a high response rate, a high rate of R0 resections, and prolonged overall survival. Cancer 2015;121:673–680. © 2014 American Cancer Society.
Photoelectron Circular Dichroism of Bicyclic Ketones from Multiphoton Ionization with Femtosecond Laser Pulses
Authors: Lux Christian , Wollenhaupt Matthias , Sarpe Cristian , Baumert Thomas
Published: December 2014

Photoelectron circular dichroism (PECD) is a CD effect up to the ten‐percent regime and shows contributions from higher‐order Legendre polynomials when multiphoton ionization is compared to single‐photon ionization. We give a full account of our experimental methodology for measuring the multiphoton PECD and derive quantitative measures that we apply on camphor, fenchone and norcamphor. Different modulations and amplitudes of the contributing Legendre polynomials are observed despite the similarity in chemical structure. In addition, we study PECD for elliptically polarized light employing tomographic reconstruction methods. Intensity studies reveal dissociative ionization as the origin of the observed PECD effect, whereas ionization of the intermediate resonance is dominating the signal. As a perspective, we suggest to make use of our tomographic data as an experimental basis for a complete photoionization experiment and give a prospect of PECD as an analytic tool.
Diazo Compounds in Continuous‐Flow Technology
Authors: Müller Simon T. R. , Wirth Thomas
Published: December 2014

Diazo compounds are very versatile reagents in organic chemistry and meet the challenge of selective assembly of structurally complex molecules. Their leaving group is dinitrogen; therefore, they are very clean and atom‐efficient reagents. However, diazo compounds are potentially explosive and extremely difficult to handle on an industrial scale. In this review, it is discussed how continuous flow technology can help to make these powerful reagents accessible on large scale. Microstructured devices can improve heat transfer greatly and help with the handling of dangerous reagents safely. The in situ formation and subsequent consumption of diazo compounds are discussed along with advances in handling diazomethane and ethyl diazoacetate. The potential large‐scale applications of a given methodology is emphasized.
Enhancing the Stability of Porphyrin Dye‐Sensitized Solar Cells by Manipulation of Electrolyte Additives
Authors: Lau Genevieve P. S. , Tsao Hoi Nok , Yi Chenyi , Zakeeruddin Shaik M. , Grätzel Michael , Dyson Paul J.
Published: December 2014

The use of porphyrin‐based photosensitizers with superior light‐harvesting properties has enabled the power conversion efficiency of dye‐sensitized solar cells (DSCs) to reach 13 % under full sun illumination. However, a major limitation of such devices corresponds to the volatility of the solvent used so far for the electrolyte, which prevents practical applications. In this work, we describe a porphyrin‐ionic liquid DSC, which not only affords the highest efficiency reported to date, but is also stable for more than 300 h under continuous full sun illumination at 60 °C. Furthermore, we identify a previously unreported pathway for device degradation, and show that the addition of N‐methylbenzimidazole and a thiocyanate salt to the electrolyte is critical to obtaining long‐lived devices.
Image based validation of dynamical models for cell reorientation
Authors: Lockley Robert , Ladds Graham , Bretschneider Till
Published: December 2014

A key feature of directed cell movement is the ability of cells to reorient quickly in response to changes in the direction of an extracellular stimulus. Mathematical models have suggested quite different regulatory mechanisms to explain reorientation, raising the question of how we can validate these models in a rigorous way. In this study, we fit three reaction–diffusion models to experimental data of Dictyostelium amoebae reorienting in response to alternating gradients of mechanical shear flow. The experimental readouts we use to fit are spatio‐temporal distributions of a fluorescent reporter for cortical F‐actin labeling the cell front. Experiments performed under different conditions are fitted simultaneously to challenge the models with different types of cellular dynamics. Although the model proposed by Otsuji is unable to provide a satisfactory fit, those suggested by Meinhardt and Levchenko fit equally well. Further, we show that reduction of the three‐variable Meinhardt model to a two‐variable model also provides an excellent fit, but has the advantage of all parameters being uniquely identifiable. Our work demonstrates that model selection and identifiability analysis, commonly applied to temporal dynamics problems in systems biology, can be a powerful tool when extended to spatio‐temporal imaging data. © 2014 The Authors. Published by Wiley Periodicals, Inc.
Peak‐to‐average power ratio reduction of a hidden training sequence‐aided precoding scheme for MIMO‐OFDM
Authors: Kim Byung Wook , Jung Sung‐Yoon
Published: December 2014

We analyze a peak‐to‐average power ratio (PAPR) reduction property based on a hidden training sequence‐aided precoding scheme for MIMO‐OFDM systems. In addition to the benefits of a hidden training sequence‐aided precoding scheme such as improvement in bandwidth efficiency and frequency diversity gain, we address that power amplifier efficiency can be improved without any additional complexity burden. By mathematically analyzing PAPR of the precoded MIMO‐OFDM signal with a hidden training sequence, we demonstrate that PAPR reduction can be obtained by varying the allocated power to the hidden training sequence. Because of the low PAPR property of this scheme, it is possible to utilize a low‐cost power amplifier, resulting in the reduction in the total cost for hardware implementation. Copyright © 2014 John Wiley & Sons, Ltd.
The use of urinary nuclear matrix protein 22 (NMP22) as a diagnostic adjunct to urine cytology for monitoring of recurrent bladder cancer—institutional experience and review
Authors: Önal Binnur , Han Ünsal , Yilmaz Sinasi , Köybasioglu Fulya , Altuğ Uğur
Published: December 2014

Background

This prospective study compares urine NMP22 immunoassay and cytomorphology for detecting recurrent urothelial carcinoma (UC) of the bladder and correlates between NMP22 levels and grade, multiplicity, and size of the tumor. We aimed refining the use of NMP22 test in the management of UC at our institution.

Methods

Urine specimens, collected prior to a cystoscopic biopsy either from patients with a history of bladder cancer (n = 50) or from controls (n = 15) were studied. Cytology and NMP22 results were compared with subsequent biopsies and performance characteristics were measured.

Results

Overall sensitivity and specificity of cytology was 62.5% and 87.5%, respectively while NMP22 had a sensitivity of 85.4% and specificity of 76.5%. NMP22 was superior to cytology for detecting low‐grade UC (82.6% vs. 54.5%) and in terms of NPV (65% vs. 44.4%) while cytology reached 100% detection rate for high‐grade UC. And, the sensitivity of 98% was achieved when NMP22 was combined with atypical cytology. Optimal performance of NMP22 has been detected around the reference value of 6.4 U/ml. The mean NMP22 values in control and study groups were 2.5 U/ml and 36 U/ml, respectively. The mean NMP22 value was 20.9 U/ml in low‐grade UC and 53.2 U/ml in high‐grade category.

Conclusions

The NMP22 values displayed higher sensitivity for low‐grade UC while cytology was highly sensitive and spesific in detection of high‐grade UC. Combining urine NMP22 assay with atypical cytology improved sensitivity for detection of recurrent UC. The inclusion of the adjunctive NMP22 test in monitoring protocols for low‐grade UC in combination with cytology for high‐grade UC could enable clinicians to decrease the frequency of follow‐up cystoscopies. Diagn. Cytopathol. 2015;43:307–314. © 2014 Wiley Periodicals, Inc.
Habitat selection and consumption across a landscape of multiple predators
Authors: Wesner Jeff S. , Meyers Peter , Billman Eric J. , Belk Mark C.
Published: December 2014

Predator community composition can alter habitat quality for prey by changing the strength and direction of consumptive effects. Whether predator community composition also alters prey density via nonconsumptive effects during habitat selection is not well known, but is important for understanding how changes to predator communities will alter prey populations. We tested the hypothesis that predator community composition (presence of caged trout, caged dragonflies, or caged trout + dragonflies) alters colonization of aquatic mesocosms by ovipositing aquatic insects. In a previous experiment in this system, we found a spatial contagion effect, in which insects avoided pools with predators, but only when predator‐free pools were isolated (~5 m away from predator pools). Here, we removed the isolated predator‐free pools, allowing us to test whether insects would make fine‐scale (~1 m) oviposition decisions in the absence of preferred isolated pools. We also estimated consumptive effects by allowing predators to feed on colonists for 5 days following colonization. All insects collected after 21 days were dipterans, dominated by Chironomidae. Total colonization, measured as the number of developing larvae after 21 days, was not affected by either predator presence or composition. Consumption was significant in the trout only treatment, reducing larval insect density by 46 ± 37% (mean ± SE). No other predator treatment significantly reduced prey density, although the proportion of chironomid larvae in protective cases increased in response to direct predation from dragonflies, indicating an antipredatory behavioral response. Taken together, these results reveal that predator community composition altered larval survival and behavior, but colonizing females either did not or could not assess these risks across small scales during oviposition.
Restoration of degraded transitional (piñon–juniper) woodland sites improves ecohydrologic condition and primes understory resilience to subsequent disturbance
Authors: Jacobs Brian F.
Published: December 2014

An overstory thinning and slash mulch treatment designed to improve ecohydrologic condition of degraded transitional (piñon–juniper) woodland sites was evaluated at four sites over a cumulative 16‐year period beginning in 1994. Study sites were located within Bandelier National Monument and Santa Fe National Forest on the east‐facing Pajarito Plateau of the Jemez Mountains in North‐Central New Mexico. Across all sites, total understory cover increased several‐fold at 3 to 5 years post‐treatment relative to both pre‐treatment condition and control, whereas measures of runoff and sediment production were reduced by an order of magnitude. During the course of post‐treatment monitoring, several coincident disturbances (multi‐year drought beginning in fall 1999, wildfire in spring 2000 and piñon ips beetle outbreak in 2002) caused widespread vegetation mortality and allowed differential recovery patterns to be documented across treatment and control areas. Response to these unplanned disturbances suggested prior restoration to improve ecohydrologic function of denuded intercanopy locations also primed understory resilience as measured by the relative capacity of restored areas to regain levels of effective cover. Treatment areas affected by drought‐beetle tree mortality exceeded pre‐drought levels of understory cover within two growing seasons while retaining improved hydrologic function; by contrast, control areas continued to exhibit accelerated runoff and erosion despite temporary improvements in understory cover post‐disturbance. Post‐fire outcomes suggest that prior restoration also enhanced levels of understory cover post‐burn relative to control, despite negative‐soil‐heating effects from consumed slash. Copyright © 2014 John Wiley & Sons, Ltd.
Sap flow and water use sources of shelter‐belt trees in an arid inland river basin of Northwest China
Authors: Shen Qin , Gao Guangyao , Fu Bojie , Lü Yihe
Published: December 2014

The knowledge of plant water use characteristics was essential for ecosystem management and water resources distribution in arid inland river basin. This study was conducted to quantify the sap flow variations and water use sources of shelter‐belt trees at the oasis–desert ecotone in the middle of China's Heihe River Basin. Sap flow was measured by the thermal dissipation method on eight Gansu Poplar (Populus gansuensis) trees with different diameter at breast height in 2012 and 2013. The mean sap flow density increased linearly with diameter at breast height. The sap flow density exhibited linear relationship with solar radiation, and it increased logarithmically with vapour pressure deficit and air temperature, whereas the water table had negative impact on sap flow. The relationship between sap flow and soil relative extractable water at 0–220 cm depth was implicit during the whole growing season, whereas the soil water had apparently positive influence on sap flow after the shelter‐belt trees irrigation. The stand transpiration rate represented as a logarithmic function of reference crop evapotranspiration. The total transpiration of Gansu Poplar during growing season was 599.3 mm, whereas only 58.1% of which was provided by the precipitation and irrigation. The groundwater and cropland irrigation were critical water sources of shelter‐belt trees. The contribution of groundwater to tree transpiration was estimated to be 35.1 and 19.0% in 2012 and 2013, respectively. The great precipitation in 2013 weakened the dependence of tree transpiration on groundwater. The estimated threshold distance of cropland irrigation influencing the tree transpiration was about 8 m. Copyright © 2015 John Wiley & Sons, Ltd.
Postulates for validating TLR4 agonists
Authors: Manček‐Keber Mateja , Jerala Roman
Published: December 2014

TLRs play a central role in the innate immune response, recognizing a variety of molecular structures characteristic of pathogens. Although TLR4, together with its co‐receptor myeloid differentiation‐2 (MD‐2), recognize bacterial LPS and therefore Gram‐negative bacterial infections, it also plays a key role in many other pathophysiological processes, including sterile inflammation and viral infection. Specifically, numerous endogenous agonists of TLR4 of notably diverse nature, ranging from proteins to metal ions, have been reported. Direct activation of a single receptor by such a range of molecular signals is very difficult to explain from a structural and mechanistic point of view. It is likely that only a subset of these directly activate the TLR4–MD‐2 complex. We propose three postulates aimed at distinguishing the direct agonists of TLR4 from indirect activators. These postulates are as follows: (i) that the agonist requires the TLR4/MD‐2 receptor complex; (ii) that agonist formed synthetically or in situ must activate the receptor complex in order to eliminate artifacts of contamination by other agonists; and (iii) that a specific molecular interaction between the agonist and TLR4/MD‐2 must be identified. The same type of postulates can be applied to pattern recognition receptors in general.
Antibodies targeting Clec9A promote strong humoral immunity without adjuvant in mice and non‐human primates
Authors: Li Jessica , Ahmet Fatma , Sullivan Lucy C. , Brooks Andrew G. , Kent Stephen J. , De Rose Robert , Salazar Andres M. , Reis e Sousa Caetano , Shortman Ken , Lahoud Mireille H. , Heath William R. , Caminschi Irina
Published: December 2014

Targeting antigens to dendritic cell (DC) surface receptors using antibodies has been successfully used to generate strong immune responses and is currently in clinical trials for cancer immunotherapy. Whilst cancer immunotherapy focuses on the induction of CD8+ T‐cell responses, many successful vaccines to pathogens or their toxins utilize humoral immunity as the primary effector mechanism. Universally, these approaches have used adjuvants or pathogen material that augment humoral responses. However, adjuvants are associated with safety issues. One approach, successfully used in the mouse, to generate strong humoral responses in the absence of adjuvant is to target antigen to Clec9A, also known as DNGR‐1, a receptor on CD8α+ DCs. Here, we address two issues relating to clinical application. First, we address the issue of variable adjuvant‐dependence for different antibodies targeting mouse Clec9A. We show that multiple sites on Clec9A can be successfully targeted, but that strong in vivo binding and provision of suitable helper T cell determinants was essential for efficacy. Second, we show that induction of humoral immunity to CLEC9A‐targeted antigens is extremely effective in nonhuman primates, in an adjuvant‐free setting. Our findings support extending this vaccination approach to humans and offer important insights into targeting design.
Uranyl–Organic Hybrids Designed from Hydroxyphosphonate
Authors: Adelani Pius O. , Martinez Nicholas A. , Cook Nathaniel D. , Burns Peter C.
Published: December 2014

A series of phosphonate‐based uranyl–organic hybrids has been assembled based on the reaction of uranyl cations with 2,5‐dihydroxy‐1,4‐benzenediphosphonic acid in the presence of a variety of alkali metal and organoammonium cations: K[(UO2)2F2{H0.5O3PC6H2(OH)2PO3H0.5}](H2O)2 (1), Cs[(UO2)2{H0.75O3PC6H2(OH)2PO3H0.75}](H2O)4·2H2O (2), [(CH3)4N]2[UO2{HO3PC6H2(OH)2PO3H}2] (3), [(CH3CH2)4N][UO2F{HO3PC6H2(OH)2PO3H}] (4), and [(CH3CH2)2N(CH3)2][UO2F{HO3PC6H2(OH)2PO3H}] (5). In compounds 1, 4, and 5, chains of UO5F2 pentagonal bipyramids are linked by the hydroxyphosphonate moiety into three‐dimensional frameworks, and compound 4 is isostructural with 5. However, the structures of 2 and 3 are composed of monomeric UO7 pentagonal bipyramids assembled to form layered structural units. Additional steric influences from the –OH groups appended on the diphosphonate species play a vital role in directing the structure topologies.
Organocatalytic Synthesis of Optically Active Organophosphorus Compounds
Authors: Dzięgielewski Marek , Pięta Jakub , Kamińska Elżbieta , Albrecht Łukasz
Published: December 2014

Owing to their wide reactivity profile, as well as a broad range of biological activity, organophosphorus compounds play a pivotal role in modern organic chemistry. Recently, much effort has been devoted to their preparation in an enantioselective fashion. This microreview summarizes the use of chiral organic molecules as catalysts in the synthesis of optically active organophosphorus compounds. Particular attention is given to the catalytic activation modes employed in the devised synthetic strategies, with special emphasis on factors governing stereochemical reaction outcomes. Furthermore, the importance of the products obtained and their selected applications are discussed.
CuSO4·5H2O‐H‐Phosphonate‐Catalyzed Intermolecular C–S Bond Formation: Synthesis of (E)‐Vinyl Alkylsulfones from Alkynes­ and DMSO
Authors: Chen Jian‐Yu , Chen Xiao‐Lan , Li Xu , Qu Ling‐Bo , Zhang Qing , Duan Li‐Kun , Xia Ying‐Ya , Chen Xin , Sun Kai , Liu Zhi‐Dong , Zhao Yu‐Fen
Published: December 2014

A CuSO4·5H2O‐H‐phosphonate‐catalyzed synthesis of (E)‐vinyl alkylsulfones from alkynes and widely available DMSO was developed. The present protocol provides an alternative approach to various vinyl sulfones, with the advantages of cheap catalysts, readily available starting materials, operational simplicity and high stereo‐ and regioselectivity.
Ruthenium‐Catalyzed Conjugate Hydrogenation of α,β‐Enones by in situ Generated Dihydrogen from Paraformaldehyde and Water
Authors: Li Wanfang , Wu Xiao‐Feng
Published: December 2014

Notwithstanding that the highly selective hydrogenation of α,β‐enones to allylic alcohols can be realized by using Noyori's Ru bifunctional system, the selective reduction of the C=C bonds in α,β‐enones without touching the C=O bonds still lacks a general, simple, and efficient procedure. Ruthenium‐catalyzed conjugate hydrogenation of various α,β‐enones to saturated ketones with high selectivity was investigated. The most important feature of this procedure was that hydrogen in situ generated from paraformaldehyde (or formalin) and water was employed as the reductant.