bluuebunny/crossref_metadata_2025 huggingface dataset:
Microencapsulation of imidazole curing agents by spray‐drying method
Authors: Lee Dong Ho , Yang Minhee , Kim Sun Hee , Shin Min Jae , Shin Jae Sup
Published: May 2011

An epoxy resin–imidazole system was used to form the adhesives for the anisotropic conducting film (ACF), and a latent curing system was necessary for the ACF. In this study, imidazoles were microencapsulated for the latent curing system. Polycaprolactone (PCL) was used as the wall material, and the spray‐drying method was used to form the microcapsule. The imidazoles used in this study were imidazole, 2‐methylimidazole, and 2‐phenylimidazole. The effect of the ratio of PCL to imidazoles, and the effect of PCL molecular weight were investigated during the microcapsule formation. The amount of imidazoles in the microcapsule was measured using thermogravimetric analyzer and elemental analysis. The permeability of the microcapsules was measured in ethanol, and the shelf life of the microcapsules was studied for the epoxy resin. The curing behavior of these microcapsules to epoxy resin was examined using differential scanning calorimeter. In the curing reaction, the microcapsule of imidazoles exhibited delayed kinetic behaviors compared to pure imidazoles. And the curing times were estimated at 150 and 180°C using an indentation method. These microcapsules of imidazoles exhibited a long shelf life, and the curing did not occur in some of the microcapsule–epoxy resin systems at 20°C for 15 days. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Genome‐wide and species‐wide dissection of the genetics of arthritis severity in heterogeneous stock mice
Authors: Johnsen Alyssa K. , Valdar William , Golden Louis , Ortiz‐Lopez Adriana , Hitzemann Robert , Flint Jonathan , Mathis Diane , Benoist Christophe
Published: May 2011

Objective

Susceptibility to inflammatory arthritis is determined by a complex set of environmental and genetic factors, but only a portion of the genetic effect can be explained. Conventional genome‐wide screens of arthritis models using crosses between inbred mice have been hampered by the low resolution of results and by the restricted range of natural genetic variation sampled. The aim of this study was to address these limitations by performing a genome‐wide screen for determinants of arthritis severity using a genetically heterogeneous cohort of mice.

Methods

Heterogeneous stock (HS) mice derive from 8 founder inbred strains by serial intercrossing (n > 60), resulting in fine‐grained genetic variation. With a cohort of 570 HS mice, we performed a genome‐wide screen for determinants of arthritis severity in the K/BxN serum–transfer model.

Results

We mapped regions on chromosomes 1, 2, 4, 6, 7, and 15 that contain quantitative trait loci influencing arthritis severity at a resolution of a few megabases. In several instances, these regions proved to contain 2 quantitative trait loci: the region on chromosome 2 included the C5 fraction of complement known to be required for K/BxN serum–transfer arthritis but also contained a second adjacent quantitative trait locus, for which an intriguing candidate is Ptgs1 (Cox1). Interesting candidates on chromosome 4 included the Padi family, encoding the peptidyl arginine deiminases responsible for citrulline protein modification; suggestively, Padi2 and Padi4 RNA expression was correlated with arthritis severity in HS mice.

Conclusion

These results provide a broad overview of the genetic variation that controls the severity of K/BxN serum–transfer arthritis and suggest intriguing candidate genes for further study.
Introduction of vertical integration and case‐based learning in anatomy for undergraduate physical therapy and occupational therapy students
Authors: Parmar Suresh K. , Rathinam Bertha A.D.
Published: May 2011

The purpose of the present pilot study was to evaluate the benefits of innovative teaching methodologies introduced to final year occupational and physical therapy students in Christian Medical College in India. Students' satisfactions along the long‐term retention of knowledge and clinical application of the respiratory anatomy have been assessed. The final year undergraduate physical therapy and occupational therapy students had respiratory anatomy teaching over two sessions. The teaching involved case‐based learning and integrated anatomy lectures (vertical integration) with the Anatomy department. Pretest and immediate and follow‐up post‐tests were conducted to assess the effectiveness of the innovative methods. A feedback questionnaire was marked to grade case‐based learning. The method of integrated and case‐based teaching was appreciated and found to be useful in imparting knowledge to the students. Students retained the gained knowledge adequately and the same was inferred by statistically significant improvement in both post‐test scores. Vertical integration of anatomy in the final year reinforces their existing knowledge of anatomy. Case‐based learning may facilitate the development of effective and clinically sound therapists. Anat Sci Educ 4:170–173, 2011. © 2011 American Association of Anatomists
Theoretical Investigation of 4,4′,6,6′‐Tetra(azido)azo‐1,3,5‐triazine‐N‐oxides and the Effects of N→O Bonding on Organic Azides
Authors: Qi Cai , Zhang Ru‐Bo , Zhang Xue‐Jiao , Li Yu‐Chuan , Wang Yuan , Pang Si‐Ping
Published: May 2011

A family of 4,4′,6,6′‐tetra(azido)azo‐1,3,5‐triazine‐N‐oxides was designed and investigated by theoretical method. The effects of the N→O bond on the properties of TAAT‐N‐oxides, such as density, heat of formation, and detonation performance, were discussed. By comparison with the bond‐dissociation energy of the weakest bond and the electrostatic potentials, the effects of the N→O bond on the stability and impact sensitivity of organic azides were also discussed. The results show that the introduction of N→O bonds at the appropriate positions increases the oxygen balance and density of the compounds, while it has little effect on the stability and impact sensitivity. Consequently, their introduction results in energetic compounds with improved detonation performances.
New Design Tactics in OLEDs Using Functionalized 2‐Phenylpyridine‐Type Cyclometalates of Iridium(III) and Platinum(II)
Authors: Zhou Guijiang , Wong Wai‐Yeung , Yang Xiaolong
Published: May 2011

As a result of their outstanding attributes, organic light‐emitting diodes (OLEDs) and white organic light‐emitting diodes (WOLEDs) have been recognized in recent years as the most promising candidates for future flat‐panel display technologies and next generation solid‐state energy‐saving lighting sources. New advancements in the area of high performance triplet emitters become vital for realizing more practical applications. In this regard, several critical issues must be carefully identified and addressed, and these include the ways to enhance device efficiency and suppress efficiency roll‐off, to achieve versatile color tuning and simple device manufacture, as well as to obtain high‐quality white light from WOLEDs. It has been shown that some functionalized phosphorescent IrIII and PtII ppy‐type cyclometalated complexes (ppy=2‐phenylpyridine) possess unique features that are suitable for solving these difficult and challenging tasks. In this Focus Review, we will highlight the recent design tactics adopted for these functional metallophosphors and the critical roles they may play in developing more realistic devices.
Exploring New Molecular Architectures for Anion Recognition: Synthesis and ATP Binding Properties of New Cyclam‐Based Ditopic Polyammonium Receptors.
Authors: Pouessel Jacky , Bazzicalupi Carla , Bencini Andrea , Bernard Hélène , Giorgi Claudia , Handel Henri , Matera Irene , Le Bris Nathalie , Tripier Raphaël , Valtancoli Barbara
Published: May 2011

Synthesis and characterization of three new polyamine receptors, composed of a cyclam unit (cyclam=1,4,8,11‐tetraazacyclotetradecane) linked by a 2,6‐dimethylpyridinyl spacer to the linear polyamines 1,4,8,11‐tetraazaundecane (L1py), 1,4,7‐triazaheptane (L2py), and to a quaternary ammonium group (L3 py+), are reported. All receptors form highly charged polyammonium cations at neutral pH, suitable for anion recognition studies. ATP recognition was analyzed by using potentiometric, calorimetric, 1H and 31P NMR measurements in aqueous solution. All receptors form 1:1 adducts with ATP in aqueous solution, stabilized by charge–charge and hydrogen‐bonding interactions between their ammonium groups and the anionic triphosphate chain of ATP. The binding ability of the three receptors for ATP increases in the order of L3 py+<L2py<L1py. These adducts are stabilized by largely favourable entropic contributions, probably due to the large desolvation of the host and guest species upon complexation. The sequence observed for the binding affinity is explained in terms of the different ability of the three receptors to wrap around the phosphate chain of ATP.
Lipid Bilayer Membrane of Egg‐PC Liposome Evaluated as Chemical Reaction Field with Picosecond Time‐Resolved Fluorescence Spectroscopy
Authors: Nojima Yuki , Iwata Koichi
Published: May 2011

Viscosity inside the lipid bilayer of egg‐PC (egg yolk phosphatidylcholine) liposome with a diameter of 100 nm is examined with picosecond time‐resolved fluorescence spectroscopy. The viscosity is estimated independently from the photoisomerization rate and from the rotational relaxation time of the first excited singlet state of trans‐stilbene solubilized within the lipid bilayer. The presence of two solvation environments within the bilayer is suggested from both of the methods. One environment is 50 to 100 times more viscous than the other. The use of trans‐stilbene as a probe provides valuable information on the solvation environments inside the lipid bilayer of liposome, which serves as a field for a number of biochemical reactions.
Transmembrane peptides used to investigate the homo‐oligomeric interface and binding hotspot of latent membrane protein 1
Authors: Sammond Deanne W. , Joce Catherine , Takeshita Ryan , McQuate Sarah E. , Ghosh Nilanjan , Martin Jennifer M. , Yin Hang
Published: May 2011

Epstein‐Barr virus (EBV), a human γ‐herpesvirus, establishes lifelong infection by targeting the adaptive immune system of the host through memory B cells. Although normally benign, EBV contributes to lymphoid malignancies and lymphoproliferative syndromes in immunocompromised individuals. The viral oncoprotein latent membrane protein 1 (LMP‐1) is essential for B lymphocyte immortalization by EBV. The constitutive signaling activity of LMP‐1 is dependent on homo‐oligomerization of its six‐spanning hydrophobic transmembrane domain (TMD). However, the mechanism driving LMP‐1 intermolecular interaction is poorly understood. Here, we show that the fifth transmembrane helix (TM5) of LMP‐1 strongly self‐associates, forming a homotrimeric complex mediated by a polar residue embedded in the membrane, D150. Replacement of this aspartic acid residue with alanine disrupts TM5 self‐association in detergent micelles and bacterial cell membranes. A full‐length LMP‐1 variant harboring the D150A substitution is deficient in NFκB activation, supporting the key role of the fifth transmembrane helix in constitutive activation of signaling by this oncoprotein. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 772‐784, 2011.
Changing clinical and pathological features of gastric cancer over time
Authors: Marrelli D , Pedrazzani C , Morgagni P , de Manzoni G , Pacelli F , Coniglio A , Marchet A , Saragoni L , Giacopuzzi S , Roviello F
Published: May 2011

Background

The aim of the present multicentre observational study was to evaluate potential changes in clinical and pathological features of patients with gastric cancer (GC) treated in a 15-year interval.

Methods

A centralized prospective database including clinical, surgical, pathological and follow-up data from 2822 patients who had resection of a primary GC was analysed. The analysis focused on three periods: 1991–1995 (period 1), 1996–2000 (period 2) and 2001–2005 (period 3). Surgical procedure, pathological classification and follow-up were standardized among centres.

Results

The number of resections decreased from 1024 in period 1 to 955 and 843 in periods 2 and 3 respectively. More advanced stages and a smaller number of intestinal-type tumours of the distal third were observed over time. Five-year survival rates after R0 resection (2320 patients) did not change over time (overall: 56·6 and 51·2 per cent in periods 1 and 3; disease-free: 66·8 and 61·1 per cent respectively). Decreases in survival in more recent years were related particularly to more advanced stage, distal tumours and tumours in women. Multivariable analysis showed a lower probability of overall and disease-free survival in the most recent interval: hazard ratio 1·22 (95 per cent confidence interval 1·06 to 1·40) and 1·29 (1·06 to 1·58) respectively compared with period 1. Recurrent tumours were more frequently peritoneal rather than locoregional.

Conclusion

Overall and disease-free survival rates after R0 resection of GC were unchanged over time.
Value of orientation training in laparoscopic cholecystectomy
Authors: Sodergren M H , Orihuela-Espina F , Froghi F , Clark J , Teare J , Yang G Z , Darzi A
Published: May 2011

Background

It is well established that disorientation during laparoscopic operations such as cholecystectomy is associated with increased morbidity and mortality. The aim of the present study was to evaluate whether high-performance orientation strategies could be taught to a cohort without relevant experience of laparoscopic cholecystectomy, resulting in improved performance and spatial awareness, thereby reducing the need for operative experience to command this skill.

Methods

Thirty medical students participated in a randomized controlled trial, with half randomized to a tutorial teaching orientation strategies at specific stages of laparoscopic cholecystectomy and half to a control group without any teaching. Attention as represented by gaze was captured using eye tracking as subjects were presented with 12 images of various stages of the operation, with the task of interpreting the orientation of the image. The primary outcome measure was subject performance in orientation. Secondary outcome measures were gaze dwell time on relevant anatomical structures within the images and comparison of individual behaviour using a visual behaviour profiling algorithm.

Results

The intervention group was significantly more likely to orientate correctly than the control group (mean 75·6 versus 56·1 per cent; P = 0·019). A difference in visual attention behaviour between the two groups was apparent for the majority of images when examining the output of the visual profiling algorithm, in the form of increased homogeneity of visual behaviour and/or an overall difference in orientation strategy. The mean orientation rate of all surgeons under identical conditions in a previously published study was 78·6 per cent.

Conclusion

Training novices in orientation strategies improved their performance significantly and it could reach the level of a surgeon with several years of experience in laparoscopic surgery.
Enhancing the translation of cancer biomarkers
Authors: Costello E , Neoptolemos J
Published: May 2011

Follow the guidelines on how to do this properly
Chemical Constituents of Cordia latifolia and Their Nematicidal Activity
Authors: Begum Sabira , Perwaiz Sobiya , Siddiqui Bina S. , Khan Shazia , Fayyaz Shahina , Ramzan Musarrat
Published: May 2011

Following nematicidal activity‐guided isolation studies on the fruits, bark, and leaves of Cordia latifolia, two new constituents, cordinoic acid (=11‐oxours‐12‐ene‐23,28‐dioic acid; 1) and cordicilin (=2‐{[(E)‐3‐(3,4‐dihydroxyphenyl)prop‐2‐enoyl]oxy}‐3‐[4‐hydroxy‐3‐(stearoyloxy)phenyl]propanoic acid; 2) were isolated from the stem and leaves, respectively, together with nine known compounds, namely cordioic and cordifolic acid from the stem bark, latifolicin A–D and rosmarinic acid from the fruits, and cordinol and cordicinol from the leaves. Their structures were determined by means of spectroscopic analyses including 1D‐ and 2D‐NMR techniques. The nematicidal activities of these constituents were determined against the root‐knot nematode Meloidogyne incognita. Hundred percent mortality was caused by all of these after 72 h at a 0.125% concentration. Compound 1 and cordioic acid were most active and caused 100% mortality after 24 h at a 0.50% concentration. Furthermore, compound 2, the ester of rosemarinic acid, was found to be more active than the free acid.
Synthesis, DNA Binding, and Cleavage Studies of Novel PNA Binding Cyclen Complexes
Authors: Zhang Yu , Wang Ming‐Qi , Zhang Ji , Zhang Da‐Wei , Lin Hong‐Hui , Yu Xiao‐Qi
Published: May 2011

A novel coumarin‐appended PNA binding cyclen derivative ligand, C1, and its copper(II) complex, C2, have been synthesized and characterized. The interaction of these compounds with DNA was systematically investigated by absorption, fluorescence, and viscometric titration, and DNA‐melting and gel‐electrophoresis experiments. DNA Melting and viscometric titration experiments indicate that the binding mode of C1 is a groove binding, and C2 is a multiple binding mode that involves groove binding and electrostatic binding. From the absorption‐titration data, we can state that the primary interaction between CT DNA and the two compounds may be H‐bonds between nucleobases. Fluorescence studies indicate that the binding ability of C1 to d(A)9 is as twice or thrice as that of other oligodeoxynucleotides. Agarose gel‐electrophoresis experiments demonstrate that C2 is an excellent chemical nuclease, which can cleave plasmid DNA completely within 24 h.
Three New Cytochalasins from the Marine‐Derived Fungus Spicaria elegans KLA03 by Supplementing the Cultures with L‐ and D‐Tryptophan
Authors: Wang Fa‐Zuo , Wei Hong‐Juan , Zhu Tian‐Jiao , Li De‐Hai , Lin Zhen‐Jian , Gu Qian‐Qun
Published: May 2011

Three new cytochalasins Z21–Z23 (1–3, resp.), together with five analogs, 4–8, were isolated from Spicaria elegans KLA03 by the OSMAC (one strain‐many compounds) approach with adding L‐ and D‐tryptophan during its cultivation. The structures of new cytochalasins were elucidated on the basis of comprehensive 1D‐ and 2D‐NMR and HR‐ESI‐MS analyses. Cytochalasins Z21 and Z22 (1 and 2, resp.), and compound 5 showed cytotoxic activities against A‐549 cell lines with IC50 values of 8.2, 20.0, and 3.1 μM, respectively.
Essential Oils of Medicinal Plants from the Central Andes of Argentina: Chemical Composition, and Antifungal, Antibacterial, and Insect‐Repellent Activities
Authors: Lima Beatriz , López Sandra , Luna Lorena , Agüero María B. , Aragón Liliana , Tapia Alejandro , Zacchino Susana , López María L. , Zygadlo Julio , Feresin Gabriela E.
Published: May 2011

The antifungal, antibacterial, and insect‐repellent activities of the essential oils (EOs) of Acantholippia seriphioides, Artemisia mendozana, Gymnophyton polycephalum, Satureja parvifolia, Tagetes mendocina, and Lippia integrifolia, collected in the Central Andes area, province of San Juan, Argentina, were investigated. The dermatophytes Microsporum gypseum, Trichophyton mentagrophytes, and T. rubrum were inhibited by the EOs of G. polycephalum, L. integrifolia, and S. parvifolia, with minimum inhibitory concentrations (MICs) between 31.2 and 1000 μg/ml. Moreover, all EOs presented moderate activity against the bacteria tested, and the L. integrifolia and G. polycephalum EOs showed excellent repellent properties against Triatoma infestans, the Chagas disease vector, with repellency values between 60 and 100%. The A. seriphioides, G. polycephalum, and L. integrifolia EOs, obtained by hydrodistillation, were characterized by GC‐FID and GC/MS analyses. The highest number of components (40) was identified in L. integrifolia EO, which, along with that of A. seriphioides, contained important amounts of oxygenated monoterpenes (44.35 and 29.72%, resp.). Thymol (27.61%) and carvacrol (13.24%) were the main components of A. seriphioides EO, and borneol, lippifoli‐1(6)‐en‐5‐one, and terpinen‐4‐ol (>8.5%) were the principal compounds of L. integrifolia EO. These results support the idea that oxygenated monoterpenes are the bioactive fractions of the EOs. Finally, the study shows that these Andean species might be used to treat superficial fungal infections and to improve the local Chagas disease situation by vector‐control.
Phytochemical and Morphological Characterization of Satureja khuzistanicaJamzad Populations from Iran
Authors: Hadian Javad , Hossein Mirjalili Mohammad , Reza Kanani Mohammad , Salehnia Alinazar , Ganjipoor Parvin
Published: May 2011

Satureja khuzistanica is an endemic herb growing wild in Iran with interesting pharmacological and biological properties. Here, as an initial step of the domestication process, the variability of phytochemical and morphological traits among 69 individuals of eight natural populations of the plant was studied. The investigated characteristics were the essential oil content and composition, the rosmarinic acid (RA) content, and the leaf and flower morphologies. The Abdanan and Kaver populations showed the highest oil contents. The characterization by GC‐FID and GC/MS analyses of the oils revealed that all 69 sampled individuals had carvacrol as the main component with very high contents (89.59–95.41%). The content of RA of the MeOH extracts of S. khuzistanica showed a high level of variability (coefficient of variation (CV) 50.0%) ranging from 0.59% (w/w) in the Paalam population to 1.81% (w/w) in the Abdanan population. The peduncle length and the leaf surface area (CVs of 47.39 and 47.21%, resp.) were the most variable morphological characteristics among the examined populations. The high level of phytochemical and morphological variability among the studied populations suggests a breeding approach during the domestication, to gain new, promising, and homogenous cultivars, attractive for the industry and agriculture.
On the Terminal Homologation of Physiologically Active Peptides as a Means of Increasing Stability in Human Serum – Neurotensin, Opiorphin, B27‐KK10 Epitope, NPY
Authors: Seebach Dieter , Lukaszuk Aneta , Patora‐Komisarska Krystyna , Podwysocka Dominika , Gardiner James , Ebert Marc‐Olivier , Reubi Jean Claude , Cescato Renzo , Waser Beatrice , Gmeiner Peter , Hübner Harald , Rougeot Catherine
Published: May 2011

The terminal homologation by CH2 insertion into the peptides mentioned in the title is described. This involves replacement of the N‐terminal amino acid residue by a β2‐ and of the C‐terminal amino acid residue by a β3‐homo‐amino acid moiety (β2hXaa and β3hXaa, resp.; Fig. 1). In this way, the structure of the peptide chain from the N‐terminal to the C‐terminal stereogenic center is identical, and the modified peptide is protected against cleavage by exopeptidases (Figs. 2 and 3). Neurotensin (NT; 1) and its C‐terminal fragment NT(8–13) are ligands of the G‐protein‐coupled receptors (GPCR) NT1, NT2, NT3, and NT analogs are promising tools to be used in cancer diagnostics and therapy. The affinities of homologated NT analogs, 2b–2e, for NT1 and NT2 receptors were determined by using cell homogenates and tumor tissues (Table 1); in the latter experiments, the affinities for the NT1 receptor are more or less the same as those of NT (0.5–1.3 vs. 0.6 nM). At the same time, one of the homologated NT analogs, 2c, survives in human plasma for 7 days at 37° (Fig. 6). An NMR analysis of NT(8–13) (Tables 2 and 4, and Fig. 8) reveals that this N‐terminal NT fragment folds to a turn in CD3OH. – In the case of the human analgesic opiorphin (3a), a pentapeptide, and of the HIV‐derived B27‐KK10 (4a), a decapeptide, terminal homologation (→3b and 4b, resp.) led to a 7‐ and 70‐fold half‐life increase in plasma (Fig. 9). With N‐terminally homologated NPY, 5c, we were not able to determine serum stability; the peptide consisting of 36 amino acid residues is subject to cleavage by endopetidases. Three of the homologated compounds, 2b, 2c, and 5c, were shown to be agonists (Fig. 7 and 11). A comparison of terminal homologation with other stability‐increasing terminal modifications of peptides is performed (Fig. 5), and possible applications of the neurotensin analogs, described herein, are discussed.
The Transaldolase Family: New Synthetic Opportunities from an Ancient Enzyme Scaffold
Authors: Samland Anne K. , Rale Madhura , Sprenger Georg A. , Fessner Wolf‐Dieter
Published: May 2011

Aldol reactions constitute a powerful methodology for carbon–carbon bond formation in synthetic organic chemistry. Biocatalytic carboligation by aldolases offers a green, uniquely regio‐ and stereoselective tool with which to perform these transformations. Recent advances in the field, fueled by both discovery and protein engineering, have greatly improved the synthetic opportunities for the atom‐economic asymmetric synthesis of chiral molecules with potential pharmaceutical relevance. New aldolases derived from the transaldolase scaffold (based on transaldolase B and fructose‐6‐phosphate aldolase from Escherichia coli) have been shown to be unusually flexible in their substrate scope; this makes them particularly valuable for addressing an expanded molecular range of complex polyfunctional targets. Extensive knowledge arising from structural and molecular biochemical studies makes it possible to address the remaining limitations of the methodology by engineering tailored biocatalysts.
Synthesis, Characterization, and DNA‐Binding and ‐Photocleavage Properties of Water‐Soluble Lanthanide Porphyrinate Complexes
Authors: Zhu Xun‐Jin , Wang Ping , Leung Heidi Wing Chi , Wong Wai‐Kwok , Wong Wai‐Yeung , Kwong Daniel W. J.
Published: May 2011

A series of cationic lanthanide porphyrinate complexes of the general formula [(Por)Ln(H2O)3]+ (Ln3+=Yb3+ and Er3+) were synthesized in moderate yields through the interaction of meso‐pyridyl‐substituted porphyrin free bases (H2Por) with [Ln{N(SiMe3)2}3]⋅x [LiCl(thf)3], and the corresponding neutral derivatives [(Por)Ln(LOMe)] (LOMe−=[(η5‐C5H5)Co{P(O)(OMe)2}3]−) were also prepared from [(Por)Ln(H2O)3]+ by the addition of the tripodal anion, LOMe−, an effective encapsulating agent for lanthanide ions. Furthermore, the water‐soluble lanthanide(III) porphyrinate complexes—including [(cis‐DMPyDPP)Yb(H2O)3]Cl3 (cis‐DMPyDPP=5,10‐bis(N‐methylpyridinium‐4′‐y1)‐15,20‐di(phenyl)porphyrin), [(trans‐DMPyDPP)Yb(H2O)3]Cl3 (trans‐DMPyDPP=5,15‐bis(N‐methylpyridinium‐4′‐y1)‐10,20‐di(phenyl)porphyrin), [(TMPyP)Yb(LOMe)]I4, and [(TMPyP)Er(LOMe)]I4 (TMPyP=tetrakis(N‐methylpyridinium‐4‐y1)porphyrin)—were obtained by methylation of the corresponding complexes with methyl iodide and unambiguously characterized. The binding interactions and photocleavage activities of the water‐soluble lanthanide(III) porphyrinate complexes towards DNA were investigated by UV‐visible, fluorescence, and near‐infrared luminescence spectroscopy, as well as circular dichroism and gel electrophoresis.
Analysis of Tertiary Phosphanes, Arsanes, and Stibanes as Bridging Ligands in Dinuclear Group 9 Complexes
Authors: Schinzel Sandra , Müller Robert , Riedel Sebastian , Werner Helmut , Kaupp Martin
Published: May 2011

The unusual bridging and semi‐bridging binding mode of tertiary phosphanes, arsanes, and stibanes in dinuclear low‐valent Group 9 complexes have been studied by density functional methods and bonding analyses. The influence of various parameters (bridging and terminal ligands, metal atoms) on the structural preferences and bonding of dinuclear complexes of the general composition [A1 M1(μ‐CH2)2(μ‐EX3)M2 A2] (M1, M2=Co, Rh, Ir; A1, A2=F, Cl, Br, I, κ2‐acac; E=P, As, Sb, X=H, F, CH3) has been analyzed. A number of factors have been identified that favor bridging or semi‐bridging modes for the phosphane ligands and their homologues. A more symmetrical position of the bridging ligand EX3is promoted by more polar EX bonding, but by less electronegative (softer) terminal anionic ligands. Among the Group 9 metal elements Co, Rh, and Ir, the computations clearly show that the 4d element rhodium exhibits the largest preference for a {M1(μ‐EX3)M2} bridge, in agreement with experimental observation. Iridium complexes should be valid targets, whereas cobalt does not seem to support well a symmetric bridging mode. Analyses of the Electron Localization Function (ELF) indicate a competition between a delocalized three‐center bridge bond and direct metal–metal bonding.
Electron Delocalization in Homoconjugated 7,7‐Diarylnorbornane Systems: A Computational and Experimental Study
Authors: Herrero‐García Noelia , Fernández Israel , Osío Barcina José
Published: May 2011

A joint computational–experimental study has been carried out to analyze the homoconjugative interactions in 7,7‐diarylnorbornane (DPN) derivatives. The experimentally observed new bands in their UV/Vis have been accurately assigned by means of TD‐DFT calculations. Both experimental data and computations show that aromatic homoconjugation in acyclic systems is an effective mechanism for electron delocalization that resembles the situation described for polyphenylenes and polyenes. The effective homoconjugation length in homoconjugated oligomers is in the range of 6–7 aryl rings. The effect of substituents directly attached to the para carbon atom of the DPN moiety have been also studied. We found that the HOMO→LUMO vertical transitions can indeed be modified by the nature of the aromatic substituents in order to provoke dramatic changes in the electronic properties (i.e., in the absorption spectra) of the studied species.
Synthesis and Characterization of Red‐Luminescent Graphene Oxide Functionalized with Silica‐Coated Eu3+ Complex Nanoparticles
Authors: Zhao Chao , Feng Lingyan , Xu Bailu , Ren Jinsong , Qu Xiaogang
Published: May 2011

Traditional dye‐doped fluorescent graphene oxide (GO) reveals a low quantum yield and a short life expectancy. Herein, red‐luminescent silica‐coated Eu3+ complex nanoparticles were synthesized and covalently coupled to GO nanosheets by means of a carbodiimide‐mediated amidation process. SEM and TEM studies demonstrated successful attachment of the silica‐coated Eu3+ complex nanoparticles onto the GO surface. Spectroscopic studies showed that the GO–nanoparticle conjugates exhibit strong luminescence, long lifetimes, as well as good photostability, which suggests that this new type of luminescent nanomaterial has the potential for highly sensitive time‐resolved fluorescence cyto‐ and histochemistry imaging.
Multiplex Detection of Endonucleases by Using a Multicolor Gold Nanobeacon
Authors: Huang Yong , Zhao Shulin , Liang Hong , Chen Zhen‐Feng , Liu Yi‐Ming
Published: May 2011

A highly sensitive and selective assay based on a novel enzyme‐responsive multicolor gold nanobeacon has been developed for the multiplex detection of endonucleases, a group of very important nucleases. The nanobeacon takes advantage of the high specificity of DNA cleavage reactions combined with the unique fluorescence‐quenching property of gold nanoparticles (AuNPs). To prepare the nanobeacon, three hairpin DNA reporters, each labeled at the 5′ terminus with a fluorescent dye (i.e., fluorescein amidite (FAM), carboxy‐X‐rhodamine (ROX), cyanine dye (Cy5)), that respond to one of three different endonucleases are co‐assembled at the surface of AuNPs (15 nm). This assembly brings the dyes into very close proximity with the AuNP, which leads to significant quenching of the fluorescence due to the nanosurface energy‐transfer (NSET) effect. When the nanobeacon is exposed to the targeted endonucleases, specific DNA cleavage occurs and pieces of DNA fragments are released from the AuNP surface along with the fluorescent dye, which results in the fluorescence recovery that provides the basis for a quantitative measurement of endonuclease activity. Three endonucleases, namely HaeIII, EcoRI, and EcoRV, were studied as the proof‐of‐concept analytes. These endonucleases in homogeneous mixture solutions were simultaneously quantified by the proposed assay with high sensitivity and specificity. The limits of detection obtained were in the range of 5.0×10−4 U mL−1 to 1.0×10−3 U mL−1 of endonuclease; these limits are at least 100 times more sensitive than the previously reported endonuclease assays. Endonuclease inhibitors impair the DNA cleavage, so it is anticipated that the present method has great potential for screening inhibitors of endonucleases. To demonstrate this application, the inhibitory effects of certain anticancer drugs on HaeIII, EcoRI, and EcoRV activities were studied. The present protocol proved to be sensitive, reliable, and easy to carry out.
Molecular Editing and Assessment of the Cytotoxic Properties of Iejimalide and Progeny
Authors: Gagnepain Julien , Moulin Emilie , Nevado Cristina , Waser Mario , Maier Armin , Kelter Gerhard , Fiebig Heinz‐Herbert , Fürstner Alois
Published: May 2011

Systematic variation of all substructures embedded into the framework of iejimalide B (2) led to a panel of synthetic analogues of this polyunsaturated macrolide, featuring structural modifications that are not accessible by derivatization of the natural lead compound itself. The assessment of the cytotoxicity of these compounds with the aid of a monolayer proliferation assay (12 human tumor cell lines in vitro) as well as a colony formation assay (24 human tumor xenografts ex vivo) revealed the exceptional potency of 2 and several of its synthetic congeners, with IC50 values in the picomolar range for the most sensitive cell lines. Whereas structural modifications of the macrocycle or of the side chain generally lead to a decrease in activity, changes of the peptidic terminus are not only well accommodated but engender increased tumor selectivity as well. 2 and two of the most promising analogues were selected for in vivo studies in mice, in which their activity against human tumor xenografts of breast cancer (MAXF 401) and prostate cancer (PRXF PC‐3M) was tested. In contrast to a previous report in the literature however, which had claimed in vivo activity for the parent iejimalides, these tests did not show a significant therapeutic effect against the chosen solid tumors upon intraperitoneal administration.
Pd‐Catalyzed [2+2+1] Coupling of Alkynes and Arenes: Phenol Diazonium Salts as Mechanistic Trapdoors
Authors: Schmidt Bernd , Berger René , Kelling Alexandra , Schilde Uwe
Published: May 2011

Alkynes and phenol diazonium salts undergo a Pd‐catalyzed [2+2+1] cyclization reaction to spiro[4,5]decatetraene‐7‐ones. This structure was confirmed for one example by X‐ray single‐crystal structure analysis. The reaction is believed to proceed through oxidative addition of the phenol diazonium cation to Pd0, subsequent insertion of two alkynes, followed by irreversible spirocyclization.
Nanometer‐Sized Reactor—A Porphyrin‐Based Model System for Anion Species
Authors: Li Yong‐jun , Zhao Ying‐jie , Flood Amar H. , Liu Chao , Liu Hui‐biao , Li Yu‐liang
Published: May 2011

Although many cagelike molecules can create a catalytic environment for promoting chemical reactions, the construction of receptors that can host anionic species and sensitize their reaction is novel. Here we report the photochemically induced dimerization of the anion radicals of TCNQ (7,7,8,8‐tetracyano‐para‐quinodimethane) in organic solvent under aerobic conditions when they are encapsulated inside a cationic photoactive receptor. There is clear evidence for a rate increase of over two orders of magnitude, photosensitization of the host, and demonstrated turnover of the catalyst.
Hydrolysis of a Basic Bismuth Nitrate—Formation and Stability of Novel Bismuth Oxido Clusters
Authors: Miersch Linda , Schlesinger Maik , Troff Ralf W. , Schalley Christoph A. , Rüffer Tobias , Lang Heinrich , Zahn Dirk , Mehring Michael
Published: May 2011

The synthesis of the nanoscaled bismuth oxido clusters [Bi38O45‐ (NO3)20(DMSO)28](NO3)4⋅4 DMSO (1 a) and [Bi38O45(OH)2(pTsO)8‐ (NO3)12(DMSO)24](NO3)2⋅4 DMSO⋅ 2 H2O (2) starting from the basic bismuth nitrate [Bi6O4(OH)4](NO3)6⋅H2O is reported herein. Single‐crystal X‐ray diffraction analysis, ESI mass spectrometry, thermogravimetric analysis, and molecular dynamics simulation were used to study the formation, structure, and stability of these large metal oxido clusters. Compounds 1 a and 2 are based on a [Bi38O45]24+ core, which is structurally related to δ‐Bi2O3. Examination of the fragmentation pathways of 1 a and 2 by infrared multi‐photon dissociation (IRMPD) tandem MS experiments allows the identification of novel bismuth oxido cluster species in the gas phase.
Correlation Between HLA‐DRB1, HLA‐DQB1 Polymorphism and Autoantibodies Against Angiotensin AT1 Receptors in Chinese Patients With Essential Hypertension
Authors: Zhu Feng , Sun Yanxiang , Wang Min , Ma Shihui , Chen Xiao , Cao Ailin , Chen Fen , Qiu Yan , Liao Yuhua
Published: May 2011

Background:

The autoantibodies (AAs) against angiotensin AT1 receptors (AT1‐AAs) have been discovered in patients with preeclampsia, malignant hypertension, and essential hypertension (EH); however, the mechanism of AA production remains to be investigated.

Hypothesis:

Polymorphisms of HLA‐DRB1 or HLA‐DQB1 are related to production of AAs in autoimmune diseases. We hypothesis that the polymorphisms of the HLA molecules are also associated with production of AT1‐AAs in patients with EH.

Methods:

We enrolled 394 patients with EH and 224 normotensive subjects in this study. Autoantibodies in sera of donors were detected by enzyme‐linked immunosorbent assay. The subjects' clinical data were collected, including gender, age, body mass index, blood pressure, smoking status, and diabetes. The patients and the normotensive subjects were classified respectively into AA‐positive and AA‐negative groups. Typing of DNA for HLA‐DRB1 and HLA‐DQB1 alleles was done by polymerase chain reaction amplification with sequence‐specific primers.

Results:

Thirteen HLA‐DRB1 and 7 HLA‐DQB1 alleles were found in this population. The frequencies of AT1‐AAs were related to blood pressure level. The frequency of AT1‐AAs in the EH group was higher than that in the normotensive group (P = 0.0001). The levels of AAs in different groups of EH show a significant difference (P = 0.027). In addition, HLA‐DRB1*04 and HLA‐DRB1*14 (odds ratio [OR]: 3.06, 95% confidence interval [CI]: 1.56–5.97, P = 0.001; and OR: 2.53, 95% CI: 1.080–5.91, P = 0.033, respectively) were related to AT1‐AA production in normotensive subjects after adjusting for covariants. The HLA‐DRB1*04 allele might be related to AT1‐AA production in hypertensive subjects, and the P value was of baseline statistical significance after adjusting for blood pressure and other covariants (OR: 1.63, 95% CI: 0.95–2.78, P = 0.070).

Conclusions:

These results suggest a difference in the immunogenetic background between the positive and negative AAs with hypertension or normotension. The HLA‐DRB1*04 allele increases the risk for AT1‐AA production. © 2011 Wiley Periodicals, Inc.

The first two authors contributed equally to this work.

This study was supported by a grant from the National Natural Science Foundation of China (No. 03600235). The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Gender‐Related Differences in Patients With ST‐Elevation Myocardial Infarction: Results From the Registry Study of the ST Elevation Myocardial Infarction Network Essen
Authors: Hailer Birgit , Naber Christoph , Koslowski Bernd , van Leeuwen Peter , Schäfer Harald , Budde Thomas , Jacksch Rainer , Sabin Georg , Erbel Raimund ,   for the Myocardial Infarction Network Essen
Published: May 2011

Background:

The Myocardial Infarction Network Essen was initiated in order to establish a standardized procedure with immediate reopening of the infarcted vessel for patients with ST‐elevation myocardial infarction (STEMI) in the city of Essen, Germany. The present study aims to evaluate gender‐related differences in presentation of disease and clinical outcome.

Hypothesis:

Gender is associated with differences in presentation and outcome of STEMI.

Methods:

All patients with STEMI were included without exception. Parameters such as risk profile, mortality, and relevant time intervals were documented. The follow‐up period was 1 year.

Results:

For this study, 1365 patients (72.1% male) were recruited. Women were significantly older, with higher prevalence of diabetes (28.1% vs 20.3%, P = 0.004) and hypertension (76.5% vs 64.8%, P<0.0005). Analysis of time intervals between symptoms to actions showed no significant differences. However, women tended to wait longer before calling for medical assistance (358 vs 331 min, P = 0.091). In‐hospital mortality was comparable with respect to gender, whereas women had higher 1‐year mortality (18.6% vs 13.2%). Age and diabetes were associated with a higher mortality. Adjusted for age, gender is no longer an independent risk factor. In the follow‐up period, significantly more women were readmitted to the hospital without a difference in the frequency of reangiography, surgery, or target‐vessel revascularization.

Conclusions:

The present data display a successful implementation of a standardized procedure in patients with STEMI. Although differences between genders are not as obvious as expected, efforts should be taken to perform a gender‐specific risk analysis as well as to promote education about proper behavior in case of new onset of angina. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
The Approach of Conformational Chimeras to Model the Role of Proline‐Containing Helices on GPCR Mobility: the Fertile Case of Cys‐LTR1
Authors: Bettinelli Ilaria , Graziani Davide , Marconi Cristina , Pedretti Alessandro , Vistoli Giulio
Published: May 2011

The homology modeling of GPCRs has benefitted vastly from the availability of some resolved structures, which allow the generation of many reliable GPCR models. However, the dynamic behavior of such receptors has been only minimally examined in silico, although several pieces of evidence have highlighted some conformational switches that can orchestrate the activation mechanism. Among such switches, Pro‐containing helices play a key role in determining bending in TM helices and thereby the width of the TM bundle. The approach proposed herein involves the generation of a set of possible models (conformational chimeras) by exhaustively combining the two main conformations (straight and bent) that a Pro‐containing helix can assume. This approach was validated by generating conformational chimeras for the Cys‐LTR1 receptor, which is involved in contractile and inflammatory processes. The generated chimeras were then used for docking a small set of representative ligands. The results revealed the flexibility mechanisms of Cys‐LTR1, showing how the docked agonists vary their stabilizing interactions, shifting from the open to closed state, and how the examined antagonists are able to block the receptor in an open and inactive conformation, thus behaving as inverse agonists. This study emphasizes the promising potential of chimera modeling, confirms the key role of proline residues in receptor activation, and suggests that docking results can be improved by considering the often‐overlooked flexibility of receptors.
Discovery of a Competitive Apelin Receptor (APJ) Antagonist
Authors: Macaluso N. J. Maximilian , Pitkin Sarah L. , Maguire Janet J. , Davenport Anthony P. , Glen Robert C.
Published: May 2011

The apelin receptor (APJ) is a class A G‐protein‐coupled receptor (GPCR) and is a putative target for the treatment of cardiovascular and metabolic diseases. Apelin‐13 (NH2‐QRPRLSHKGPMPF‐COOH) is a vasoactive peptide and one of the most potent endogenous inotropic agents identified to date. We report the design and discovery of a novel APJ antagonist. By using a bivalent ligand approach, we have designed compounds with two ′affinity′ motifs and a short series of linker groups with different conformational and non‐bonded interaction properties. One of these, cyclo(1–6)CRPRLC‐KH‐cyclo(9–14)CRPRLC is a competitive antagonist at APJ. Radioligand binding in CHO cells transfected with human APJ gave a Ki value of 82 nM, competition binding in human left ventricle gave a KD value of 3.2 μM, and cAMP accumulation assays in CHO‐K1‐APJ cells gave a KD value of 1.32 μM.
Cytopathology of “double‐hit” non‐Hodgkin lymphoma
Authors: Elkins Camille T. , Wakely Paul E.
Published: May 2011

BACKGROUND:

B‐cell lymphomas with concurrent IGH‐BCL2 and c‐MYC rearrangements (so‐called “double‐hit lymphomas” [DHL]) are a relatively rare, recently described category in the 2008 World Health Organization classification of hematopoietic neoplasms. Response to chemotherapy and survival are poor.

METHODS:

The authors reviewed files of cytogenetically documented DHL to identify cytologic features that would allow its possible recognition.

RESULTS:

Twelve fine‐needle aspirates (FNAs), 2 pleural fluids, and 1 touch imprint of cytogenetically proven DHL were uncovered. Primary DHL was correctly recognized in 3 of 12 FNA cases using Ki‐67 staining coupled with a positive bcl‐2 result as the basis for performing fluorescence in situ hybridization (FISH) analysis of c‐MYC and IGH‐BCL2 rearrangements. Remaining FNAs and non‐FNA cases were diagnosed as non‐Hodgkin lymphoma, B‐cell lymphoma, or atypical lymphocytosis. Ten cases had cell block material available. All cases had high cellularity with a dissociated smear pattern and background lymphoglandular bodies. Cell size ranged from intermediate to large. Nuclei were predominantly rounded or slightly irregular in contour; 4 FNAs had markedly cleaved nuclei. Some nuclei harbored discrete but small nucleoli, whereas in others coarse chromatin and indistinct or multiple small nucleoli existed. A variable number of mitotic figures, tingible body macrophages, and background apoptotic cells were also present.

CONCLUSIONS:

No specific cytomorphologic feature(s) were found to reliably identify DHL using FNA or exfoliative cytology. A high Ki‐67 proliferation index and positive bcl‐2 staining (on cytospin slides or cell block material) of cases not conforming to typical Burkitt lymphoma morphology should prompt FISH analysis for c‐MYC and/or IGH‐BCL2 rearrangements to identify DHL, particularly if tissue biopsy is not expected. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society
Dancing on DNA: Kinetic Aspects of Search Processes on DNA
Authors: Tafvizi Anahita , Mirny Leonid A. , van Oijen Antoine M.
Published: May 2011

Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the search for its target site, the DNA‐associated protein is facing both thermodynamic and kinetic difficulties. The thermodynamic challenge lies in recognizing and tightly binding a cognate (specific) site among the billions of other (non‐specific) sequences on the DNA. The kinetic difficulty lies in finding a cognate site in mere seconds amidst the crowded cellular environment that is filled with other DNA sequences and proteins. Herein, we discuss the history of the DNA search problem, the theoretical background and the various experimental methods used to study the kinetics of proteins searching for target sites on DNA.
Composition and morphology control of Fex(PO4)y(OH)z·nH2O microcrystals
Authors: Ming Hai , Yu Hang , Wei Huaixin , Liu Yang , Li Haitao , He Xiaodie , Huang Hui , Kang Zhenhui
Published: May 2011

A series of Fex(PO4)y(OH)z·nH2O microcrystals were prepared by the hydrothermal reaction at 150 °C. The ratio of Fe2+/Fe3+ in Fex(PO4)y(OH)z·nH2O microcrystals can be adjusted by using Na2S2O3·5H2O as a reducing agent. The morphology control of Fex(PO4)y(OH)z·nH2O microcrystals was realized through regulating the molar ratio of LiAc·2H2O/FeCl3. Further, the morphology, structure and composition of Fex(PO4)y(OH)z·nH2O microcrystals were also investigated by x‐ray diffraction (XRD), x‐ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) techniques. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)