bluuebunny/crossref_metadata_2025 huggingface dataset:
The Chemistry and Biology of Trypanosomal trans‐Sialidases: Virulence Factors in Chagas Disease and Sleeping Sickness
Authors: Schauer Roland , Kamerling Johannis P.
Published: September 2011

trans‐Sialidases constitute a special group of the sialidase family. They occur in some trypanosome species and, in a unique reversible reaction, transfer sialic acids from one glycosidic linkage with galactose (donor) to another galactose (acceptor), to form (α2–3)‐sialyl linkages. Trypanosomes cause such devastating human diseases as Chagas disease in South America (Trypanosoma cruzi) or sleeping sickness in Africa (Trypanosoma brucei). The trans‐sialidases strongly contribute to the pathogenicity of the trypanosomes by scavenging sialic acids from the host or blood meal to coat the parasite surface; this aids their survival strategy in the insect′s intestine, and in the blood circulation or cells of the host, and serves to compromise the immune system of the human or animal host. American and African trypanosomes express trans‐sialidases at different stages of their vector/host development. They are transmitted to humans by insect vectors (tsetse fly or other insect “bug” species). trans‐Sialidase activity with varying linkage specificity has also been found in a few bacteria species and in human serum. trans‐Sialidases are of increasing practical importance for the chemo‐enzymatic synthesis of sialylated glycans. The search for appropriate inhibitors of trans‐sialidases and vaccination strategies is intensifying, as less toxic medicaments for the treatment of these widespread and often chronic tropical diseases are required.
The Binding Mode of Cladocoran A to the Human Group IIA Phospholipase A2
Authors: Monti Maria Chiara , Chini Maria Giovanna , Margarucci Luigi , Riccio Raffaele , Bifulco Giuseppe , Casapullo Agostino
Published: September 2011

The molecular basis for human group IIA phospholipase A2 inactivation by the marine natural product cladocoran A (CLD A) has been studied in order to elucidate its relevant anti‐inflammatory properties. Indeed, secretory phospholipases A2 are well‐known to be implicated in the pathogenesis of inflammation, such as rheumatoid arthritis, septic shock, psoriasis and asthma, thus the understanding of their inactivation mechanism could be useful for the development of new chemical classes of selective inhibitors. Our results, collected by a combination of biochemical approaches, advanced mass spectrometry and molecular modeling, suggest a competitive inhibition mechanism guided by a noncovalent molecular recognition event, and disclose the key role of the CLD A γ‐hydroxybutenolide ring in the chelation of the catalytic calcium ion inside the enzyme active site. Moreover, CLD A is able to react selectively with Ser82, although this covalent event seems to play a secondary role in terms of enzyme inhibition.
Two Pathways for Pyrrole Formation in Coumermycin A1 Biosynthesis: The Central Pyrrole Moiety Is Formed From L‐Threonine
Authors: Siebenberg Stefanie , Burkard Nadja , Knuplesch Anna , Gust Bertolt , Grond Stephanie , Heide Lutz
Published: September 2011

Coumermycin A1 is an aminocoumarin antibiotic produced by Streptomyces rishiriensis. It contains three pyrrole rings, that is, two terminal 5‐methyl‐pyrrole‐2‐carboxyl moieties and a central 3‐methylpyrrole‐2,4‐dicarboxylic acid moiety. The biosynthesis of the terminal pyrrole moieties has been elucidated previously. However, the biosynthetic precursors of the central pyrrole moiety have remained unknown, and none of the genes or enzymes involved in its formation has been identified. We now show that five genes, contained in a contiguous 4.7 kb region within the coumermycin biosynthetic gene cluster, are required for the biosynthesis of this central pyrrole moiety. Each of these genes was deleted individually, resulting in a strong reduction or an abolishment of coumermycin production. External feeding of the central pyrrole moiety restored coumermycin production. One of these genes shows similarity to L‐threonine kinase genes. Feeding of [U‐13C,15N]L‐threonine and 13C NMR analysis of the resulting compound unequivocally proved that threonine was incorporated intact into the central pyrrole (19 % enrichment) to provide the heterocyclic nitrogen as well as four of the seven carbons of this moiety. Therefore, this pyrrole is formed via a new, hitherto unknown biosynthetic pathway. A hypothesis for the reaction sequence leading to the central pyrrole moiety of coumermycin A1 is presented.
Deweyan democratic learning communities and student marginalization
Authors: Harbour Clifford P. , Ebie Gwyn
Published: September 2011

Community college faculty and staff committed to the eradication of student marginalization may use a variety of contemporary strategies to address this form of oppression. We seek to complement these strategies by showing how the work of John Dewey may be used to justify the creation and development of democratic learning communities fundamentally opposed to student marginalization.
Noncredit to credit transitioning matters for adult ESL learners in a California community college
Authors: Becker Liza A.
Published: September 2011

This chapter raises awareness of the role that educational and socioeconomic background plays in the perceived sense of marginality and the decision‐making process for adult immigrant learners who are preparing to transition from the highest levels of noncredit ESL to credit programs and postsecondary degree pathways.
Angioscopy study from a large patient population comparing sirolimus‐eluting stent with biodegradable versus durable polymer
Authors: Chen Shao‐Liang , Xu Tian , Zhang Jun‐Jie , Ye Fei , Hu Zuo‐Ying , Tian Nai‐Liang , Zhang Yao‐Jun , Kotani Junichi , Zhang Jun‐Xia
Published: September 2011

Aims: This study aimed to compare the neointimal coverage (NIC), subclinical thrombus, color of plaque underneath the stent at 9‐month after implantation of sirolimus‐eluting stent (SES) either with durable or with biodegradable polymer (BDPM). Methods: A total of 175 patients were assigned as Cypher (n = 81, 97 stents with durable polymer) and Excel (n = 94, 112 stents with BDPM) stent at 9‐month after indexed procedure. NIC was classified from grade 0–3. Color of plaque was divided into white, light‐yellow, yellow, and dark yellow. Thrombus was diagnosed as white or red material with cotton‐like or ragged appearance. Incomplete NIC (grade 0/1) circled by a blush was termed by “inflaming.” Results: There were significant differences in unstable angina (90.5 vs. 52.4%, P = 0.015), previous myocardial infarction (33.3 vs. 4.0%, P = 0.045) and left ventricular eject fraction (55.2 ± 7.8 vs. 62.6 ± 6.3%, P = 0.021) between the Excel and Cypher groups. The minimal‐ and maximal‐NIC grades in the Cypher group were 0.67 ± 0.58 and 2.29 ± 0.46, respectively, when compared with 1.45 ± 0.67 (P < 0.001) and 2.64 ± 0.49 (P = 0.023) in the Excel group. The percentage of yellow plaque, thrombus, “inflaming” and NIC grade of 0 in the Excel and Cypher groups, respectively, were as follows: 8.0 vs. 26.8% (P = 0.031), 9.8 vs. 32.9% (P = 0.024), 8.0 vs. 38.1% (P = 0.017), and 38.1 vs. 0% (P < 0.001). Of the stents with “inflaming,” 63.6% had thrombus when compared with 20.1% of the non‐erosion stents (P < 0.001). Overlapping segments had the lowest NIC grades and more “inflaming” demonstrating a significant difference between Cypher vs. Excel stents. NIC grade was positively correlated with thrombus. Conclusions: SES with BDPM has improved NIC resulting in less yellow plaque, thrombus, and “inflaming.” Overlapping segments had the lowest NIC grade and more “inflaming.” © 2012 Wiley Periodicals, Inc.
Multiple cerebral emboli following dislocation and retraction of a partially deployed CoreValve prosthesis during transcatheter aortic valve implantation
Authors: Fairbairn Timothy A. , Greenwood John P. , Blackman Daniel J.
Published: September 2011

Transcatheter aortic valve implantation for patients with severe aortic stenosis at a high‐operative risk has been demonstrated to improve mortality compared to standard medical therapy. Registry data and the PARTNER trial have shown a significant risk of stroke (3–5%) following the procedure. Studies using cerebral diffusion‐weighted magnetic resonance imaging have suggested the mechanism of stroke to be multiple small embolic infarcts, possibly from aortic atheroma dislodged during the movement of the valve and its apparatus around the thoracic aorta. The incidence of these infarcts is higher than clinically apparent. The Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) prosthesis is a self‐expanding nitinol frame with porcine valve, whose deployment is achieved by the retraction of the delivery catheter. Potential complications of this method include valve mal‐positioning and dislocation. The partially deployed valve may then be resheathed following retraction back into the descending aorta and subsequently redeployed. We present two such cases with evidence of both “silent” and clinically evident cerebral infarction. © 2013 Wiley Periodicals, Inc.
Predictors of reintervention in neonates with critical pulmonary stenosis or pulmonary atresia with intact ventricular septum
Authors: Shaath Ghassan , Al Mutairi Mansour , Tamimi Omar , Alakhfash Ali , Abolfotouh Mostafa , Alhabshan Fahad
Published: September 2011

Objectives: Describe the short and midterm outcome and to determine the predictors of reintervention in neonates with critical pulmonary stenosis (PS) or pulmonary atresia with intact ventricular septum (PA/IVS). Background: The transcatheter intervention for critical PS and PA/IVS resulted in improvement in the patient's survival and the quality of life. The procedure is not free of complications and there is still a significant rate of reintervention. Method: All neonates with critical PS or PA/IVS who underwent interventional cardiac catheterization between November 2004 and January 2009 were reviewed retrospectively. We performed a comparison between those who required reintervention and those who did not, to identify the predictors of reintervention. Results: Forty‐three neonates were included, 23 (53.5%) had critical PS and 20 (46.5%) had PA/IVS. Twenty‐six patients (60%) were males, the mean age was 11 ± 8 days, and the mean weight was 3.2 ± 0.6 kg. Two patients died (4.6%). The mean follow‐up period was 19 ± 13 months for 42 patients. Fifteen patients (36%) required reintervention, 11 of them (73%) had PA/IVS, and 4 (27%) had critical PS. Reintervention was more in patients with PA/IVS than those with critical PS (P = 0.003). Other predictors for reintervention included hospital stay ≥ 7.5 days (P = 0.001) and tricuspid valve regurgitation peak gradient in day one post first intervention (TR1) ≥ 43 mm Hg (P = 0.03). Conclusion: Interventional cardiac catheterization shows favorable outcome for patients with critical PS and PA/IVS. Predictors for reintervention included the diagnosis of PA/IVS, hospital stay ≥7.5 days after first intervention and TR1 gradient ≥ 43 mm Hg. © 2011 Wiley Periodicals, Inc.
Intracardiac echocardiography and fluoroscopy guided percutaneous left ventricular pseudoaneurysm closure
Authors: Melman Yonathan F. , Levy Michael S. , Laham Roger J.
Published: September 2011

Left ventricular (LV) pseudoaneurysm is a rare complication after myocardial infarction and cardiac surgery. Standard treatment remains surgical correction; however, percutaneous closure has been attempted in high risk surgical patients. We report a case of three dimensional echocardiography and cardiac CT defined LV pseudoaneurysm which was closed percutaneously using intracardiac echocardiography (ICE) and fluoroscopy guidance. Appropriate planning and guidance proved essential to the procedure with an excellent outcome. Percutaneous closure of LV pseudoaneurysms is safe and feasible in high risk surgical patients and with appropriate imaging modalities may be an alternative to surgical correction. © 2011 Wiley Periodicals, Inc.
Left ventricular noncompaction and aneurysm revealed by left ventriculography
Authors: Ionescu Costin Nicolae , Turcot Diane
Published: September 2011

Left ventriculography (LVG) is sometimes not performed during cardiac catheterization when results of prior noninvasive tests are available. We present a rare case of left ventricular noncompaction coexisting with left ventricular aneurysm diagnosed during cardiac catheterization. LVG could provide additional information in patients with nonobstructive coronary artery disease and decreased ejection fraction on noninvasive tests. © 2011 Wiley Periodicals, Inc.
Aortic valve annulus diameter in chinese patients with severe calcific aortic valve stenosis: Implications for transcatheter aortic valve implantation
Authors: Pan Wenzhi , Zhou Daxin , Pan Cuizhen , Ge Junbo
Published: September 2011

Objectives: The objective of the study was to describe the distribution and determine the predictors of aortic valve annulus diameter (AVAD) in Chinese patients with severe calcific aortic valve stenosis (CAS). Background: AVAD in Chinese patients with CAS has not been reported. Predictors of AVAD in patients with CAS are unclear. Methods: One hundred elderly patients (≥60 years) with severe CAS were included in the study. AVAD in all patients was measured by transthoracic echocardiograph (AVAD‐TTE) and in 74 patients of them was measured intra‐operatively (AVAD‐intra). Results: The intraclass correlation coefficient (ICC) between AVAD‐TTE and AVAD‐intra was 0.81 (95% CI: 0.72–0.88). The differences between AVAD‐TTE and AVAD‐intra ranged from −3 to 3 mm and were ≤≤ 2mm in 91.9% (68/74) of patients. The intra‐observer ICC for TTE was 0.87 (95% CI: 0.74–0.94). Mean AVAD in the whole population was 21.80 ± 2.09 (17–27) mm. 11% of cases had an AVAD < 20 mm, 78% had an AVAD between 20 and 24 mm, and 11% had an AVAD between 25 and 27 mm. The correlation between AVAD and height (r = 0.476, P < 0.001) was stronger than that between AVAD and weight (r = 0.215, P = 0.034) or body surface area (BSA) (r = 0.358, P < 0.001). Multivariate regression showed that height, sex, and age but not BSA were independent predictors of AVAD (all P < 0.05). Conclusion: Most of Chinese patients with CAS can be candidates for transcatheter aortic valve implantation procedure in terms of AVAD, whereas more sizes of prosthetic valves need to be developed. Sex, age, and especially height, but not BAS, are independent predictors of AVAD in patients with CAS. © 2011 Wiley Periodicals, Inc.
The role of embolic protection devices during carotid stenting prior to cardiac surgery in asymptomatic patients: Empty filters?
Authors: Van der Heyden Jan , Wolters Frank J. , Garin Nathalie , Blant Snezana Andrejevic , Inglin Marc , Bal E.T. , Suttorp Jan‐Maarten
Published: September 2011

Objectives: The purpose of this study was to analyze the debris captured in the distal protection filters used during carotid artery stenting (CAS). Background: CAS is an option available to high‐risk patients requiring revascularization. Filters are suggested for optimal stroke prevention during CAS. Methods: From May 2005 to June 2007, filters from 59 asymptomatic patients who underwent CAS were collected and sent to a specialized laboratory for light‐microscope and histological analysis. Peri‐ and postprocedural outcomes were assessed during 1‐year follow‐up. Results: On the basis of biomedical imaging of the filter debris, the captured material could not be identified as embolized particles from the carotid plaque. On histological analysis the debris consisted mainly of red blood cell aggregates and/ or platelets, occasionally accompanied by granulocytes. We found no consistent histological evidence of embolized particles originating from atherosclerotic plaques. Post‐procedure, three neurological events were reported: two (3.4%) transient ischemic attacks (TIA) and one (1.7%) ipsilateral minor stroke. Conclusion: The filters used during CAS in asymptomatic patients planned for cardiac surgery often remained empty. These findings may be explained by assuming that asymptomatic patients feature a different atherosclerotic plaque composition or stabilization through antiplatelet medication. Larger, randomized trials are clearly warranted, especially in the asymptomatic population. © 2012 Wiley Periodicals, Inc.
Pentadecyl Phenol‐ and Cardanol‐Functionalized Fluorescent, Room‐Temperature Liquid‐Crystalline Perylene Bisimides: Effect of Pendant Chain Unsaturation on Self‐Assembly
Authors: Bhavsar Ghanashyam A. , Asha S. K.
Published: September 2011

A new perylene bisimide (PBI) building block based on pentadecyl phenol (PDP) or cardanol was developed, which upon esterification with 3,4,5‐tridodecyloxy gallate resulted in highly emissive, room‐temperature liquid‐crystalline (LC) molecules. The self assembly in solution was studied in detail by NMR spectroscopy, UV/Vis absorption, and fluorescence spectroscopy. In solution both PDP‐ and cardanol‐based PBI exhibited similar behavior. They were molecularly dissolved in chloroform (CHCl3) but formed rotationally displaced H‐type aggregates that emitted at 640 nm in methylcyclohexane (MCH). Surface morphology in dropcast films were characterized using microscopic techniques such as SEM, TEM, and atomic force microscopy (AFM). The liquid‐crystalline properties were studied using differential scanning calorimetry (DSC), polarized light microscopy (PLM), and variable‐temperature X‐ray (small‐angle X‐ray scattering (SAXS) and wide‐angle X‐ray diffraction (WXRD)) studies. Variable‐temperature X‐ray studies in the LC phase indicated strong π–π stacking interaction present in the PDP‐based PBI derivative, whereas the stacking was absent in the LC phase of the cardanol‐based PBI. The latter formed self‐organized structures of extremely short length due to the presence of cis double bonds in the C15 alkyl side chain, whereas the saturated alkyl side chain in PDP could pack efficiently, thereby resulting in nanofibers that were several micrometers in length.
A 1,2,3,4,5‐Pentaphenylferrocene‐Stoppered Rotaxane Capable of Electrochemical Anion Recognition
Authors: Evans Nicholas H. , Serpell Christopher J. , White Nicholas G. , Beer Paul D.
Published: September 2011

The chloride anion templated synthesis of an electrochemical anion sensory interlocked host system, prepared by the integration of redox‐active 1,2,3,4,5‐pentaphenylferrocene stopper groups into the structure of a rotaxane capable of binding anionic guests is described. Extensive 1H NMR and electrochemical titration investigations were used to probe the anion recognition and sensing properties of the rotaxane, compared to the axle and model system components. A characteristic electrochemical response was observed for chloride binding by the rotaxane, which was attributed to the topologically constrained cavity of the interlocked host molecule.
Molecular‐Beacon‐Based Tricomponent Probe for SNP Analysis in Folded Nucleic Acids
Authors: Nguyen Camha , Grimes Jeffrey , Gerasimova Yulia V. , Kolpashchikov Dmitry M.
Published: September 2011

Hybridization probes are often inefficient in the analysis of single‐stranded DNA or RNA that are folded in stable secondary structures. A molecular beacon (MB) probe is a short DNA hairpin with a fluorophore and a quencher attached to opposite sides of the oligonucleotide. The probe is widely used in real‐time analysis of specific DNA and RNA sequences. This study demonstrates how a conventional MB probe can be used for the analysis of nucleic acids that form very stable (Tm>80 °C) hairpin structures. Here we demonstrate that the MB probe is not efficient in direct analysis of secondary structure‐folded analytes, whereas a MB‐based tricomponent probe is suitable for these purposes. The tricomponent probe takes advantage of two oligonucleotide adaptor strands f and m. Each adaptor strand contains a fragment complementary to the analyte and a fragment complementary to a MB probe. In the presence of a specific analyte, the two adaptor strands hybridize to the analyte and the MB probe, thus forming a quadripartite complex. DNA strand f binds to the analyte with high affinity and unwinds its secondary structure. Strand m forms a stable complex only with the fully complementary analyte. The MB probe fluorescently reports the formation of the quadripartite associate. It was demonstrated that the DNA analytes folded in hairpin structures with stems containing 5, 6, 7, 8, 9, 11, or 13 base pairs can be detected in real time with the limit of detection (LOD) lying in the nanomolar range. The stability of the stem region in the DNA analyte did not affect the LOD. Analytes containing single base substitutions in the stem or in the loop positions were discriminated from the fully complementary DNA at room temperature. The tricomponent probe promises to simplify nucleic acid analysis at ambient temperatures in such applications as in vivo RNA monitoring, detection of pathogens, and single nucleotide polymorphism (SNP) genotyping by DNA microarrays.
Seasonal Thermal Energy Stores – Design, Operation and Applications
Authors: Marx Roman , Nußbicker‐Lux Janet , Bauer Dan , Heidemann Wolfgang , Drück Harald
Published: September 2011

Die saisonale Speicherung von Solarwärme oder Abwärme aus Kraft‐Wärmekopplungsanlagen kann maßgeblich dazubeitragen, in zukünftigen Energiewandlungssystemen fossile Brennstoffe zu einem großen Anteil zu ersetzen. Solar unterstützte Nahwärmeversorgungsanlagen in Kombination mit Langzeit‐Wärmespeichern ermöglichen solare Deckungsanteile am Gesamtwärmebedarf von 50 % und mehr. Durch den Bau und Betrieb mehrerer Pilotanlagen zur solar unterstützten Nahwärmeversorgung mit saisonaler Wärmespeicherung in Deutschland seit 1996 konnten die hohen erzielbaren solaren Deckungsanteile bestätigt werden. Vier unterschiedliche Bauarten für Langzeit‐Wärmespeicher wurden entwickelt, unter realen Betriebsbedingungen getestet und langzeitüberwacht: Heißwasser‐, Kies/Wasser‐, Erdsonden‐ und Aquifer‐Wärmespeicher.
Petri Net Based Metabolic Network Parameters Fitting with GPU Acceleration
Authors: Gao Jun , Zhu Ruixin , Liu Qi , Cao Zhiwei
Published: September 2011

Classical Petri net has been applied into biological analysis, especially as a qualitative model for biochemical pathways analysis, but lack of the ability for quantitative kinetic simulations. In our study, we presented an integration work of the qualitative model–Petri nets with the quantitative approach‐ordinary differential equations (ODEs) for the modeling and analysis of metabolic networks. As an application of our study, the computational modeling of arachidonic acid (AA) biochemical network was provided. A Petri net was set up to present the constraint‐based dynamic simulations on AA metabolic network combined with the validated ODEs model. Furthermore, Graphics Processing Unit (GPU) was adopted to accelerate the calculation of kinetic parameters unavailable from experiments. Our results have indicated that the proposed simulation method was practicable and useful with GPU acceleration, and provides new clues for the large‐scale qualitative and quantitative models of biochemical networks.
Development of a Rapid and Simultaneous Detection Method for Buprenorphine, Norbuprenorphine and Naloxone in Human Plasma Using Ultra‐high Performance Liquid Chromatography‐tandem Mass Spectrometer with Solid‐phase Extraction
Authors: Guo Qiaozhen , Du Zhenxia
Published: September 2011

A simultaneous method was successfully established and validated for the separation and determination of buprenorphine (BP), its primary metabolite, nor‐buprenorphine (NBP) and a proposed co‐formulate, naloxone (NLX) in human plasma. The method used buprenorphine‐d4 (BP‐D4), nor‐buprenorphine‐d3 (NBP‐D3), naltrexone (NTX) as internal standards (ISs). 100 μL of plasma sample fortified with the ISs was cleaned up by solid‐phase extraction (SPE), and was then separated on a Waters AcquityTM BEH C18 column with gradient elution using methanol and water (containing 0.2% formic) at a flow rate of 0.25 mL·min−1. The mass spectrometer was used for detection and was operated in the positive electrospray ionization with multiple reaction monitoring (MRM) mode. The three compounds were effectively separated in 5 min. The linear ranges of the compounds were 0.1–25, 0.25–25 and 0.05–25 ng·mL−1 for BP, NBP and NLX, respectively, with r≧0.9935. The method had high sensitivity (the limits of detection were 0.02, 0.1 and 0.01 ng·mL−1 for BP, NBP and NLX, respectively) and high recoveries (≧97.6%). The result was shown to be linear and satisfactorily met current acceptance criteria for validation of bioanalytical method: intra and inter assay precisions within the required limits of ≦25% RSD. The LOQs fulfilled the LOQ requirements: precision≦25% RSD, and was fully validated according to the State Food and Drug Administration (SFDA) regulations. The results demonstrated that ultra‐high performance liquid chromatography‐tandem mass spectrometer (UPLC‐MS/MS) with SPE was a powerful detection tool and contributed to pharmaceutical analysis in biological matrices.
Novel Cross‐Linked Conducting Polythiophene with Yellow‐Green‐Light‐Emitting Properties and Good Thermal Stability
Authors: Lai Cunyuan , Guo Wenjuan , Tang Xinde , Zhang Guangyou , Pan Qiwei , Pei Meishan
Published: September 2011

A novel conjugated polythiophene derivative with polymethacrylate attaching to the polymer backbone via an alkyl spacer was successfully synthesized. A methacrylate‐substituted thiophene monomer, 3‐(hexyl methacrylate)thiophene was prepared and polymerized by free radical polymerization, followed by an electrochemical polymerization. The resulting polymer as a yellow‐green‐light emitter, has potential applications in photoelectronics area.
Silicon Analogues of the Nonpeptidic GnRH Antagonist AG‐045572: Syntheses, Crystal Structure Analyses, and Pharmacological Characterization
Authors: Barnes Matthew J. , Burschka Christian , Büttner Matthias W. , Conroy Richard , Daiss Jürgen O. , Gray Ian C. , Hendrick Alan G. , Tam L. H. , Kuehn Diana , Miller David J. , Mills John S. , Mitchell Philip , Montana John G. , Muniandy Parameswary A. , Rapley Helen , Showell Graham A. , Tebbe David , Tacke Reinhold , Warneck Julie B. H. , Zhu Bin
Published: September 2011

AG‐045572 (CMPD1, 1 a) is a nonpeptidic gonadotropin‐releasing hormone (GnRH) antagonist that has been investigated for the treatment of sex hormone‐related diseases. In the context of systematic studies on sila‐substituted drugs, the silicon analogue disila‐AG‐045572 (1 b) and its derivative 2 were prepared in multi‐step syntheses and characterized by elemental analyses (C, H, N), NMR spectroscopic studies (1H, 13C, 29Si), and single‐crystal X‐ray diffraction. The pharmacological properties of compounds 1 a, 1 b, and 2 were compared in terms of their in vitro potency at cloned human and rat GnRH receptors. Compounds 1 a and 2 were also examined in regard to their pharmacokinetics and in vivo efficacy in both castrated rat (luteinizing hormone (LH) suppression) and intact rat (testosterone suppression) models. The efficacy and pharmacokinetic profiles of 1 a and its silicon‐containing analogue 2 appear similar, indicating that replacement of the 5,6,7,8‐tetrahydronaphthalene ring system by the 1,3‐disilaindane skeleton led to retention of efficacy. Therefore, the silicon compound 2 represents a novel drug prototype for the design of potent, orally available GnRH antagonists suitable for once‐daily dosing.
Regularization of voxelwise autoregressive model for analysis of functional magnetic resonance imaging data
Authors: Ahmad Fayyaz , Maqbool M. , Lee Namgil
Published: September 2011

This study reports the construction of a simple and elegant method to improve the detection of brain regions with increased neuronal activity in functional magnetic resonance imaging (fMRI). The main advantages of the method are regularization of voxelwise autoregressive parameters and accurate estimation of parameters and statistical inferences as compared to the conventional restricted maximum likelihood (ReML) method, where each voxel uses the two voxel‐wide (global) hyperparameters. The model is tested for its accuracy and efficiency in analysis of fMRI data for stimulated and real brains of healthy individuals. Receiver operating characteristic curves are used to show that the proposed method is superior to the conventional ReML method. The proposed method will improve the diagnostic accuracy of fMRI studies in the human brain. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part A 38: 187–196, 2011.
Tensors and rotations in NMR
Authors: Mueller Leonard J.
Published: September 2011

The transformation of second‐rank Cartesian tensors under rotation plays a fundamental role in the theoretical description of nuclear magnetic resonance experiments, providing the framework for describing anisotropic phenomena such as single crystal rotation patterns, tensor powder patterns, sideband intensities under magic‐angle sample spinning, and as input for relaxation theory. Here, two equivalent procedures for effecting this transformation—direct rotation in Cartesian space and the decomposition of the Cartesian tensor into irreducible spherical tensors that rotate in subgroups of rank 0, 1, and 2—are reviewed. In a departure from the standard formulation, the explicit use of the spherical tensor basis for the decomposition of a spatial Cartesian tensor is introduced, helping to delineate the rotational properties of the basis states from those of the matrix elements. The result is a uniform approach to the rotation of a physical system and the corresponding transformation of the spatial components of the NMR Hamiltonian, expressed as either Cartesian or spherical tensors. This clears up an apparent inconsistency in the NMR literature, where the rotation of a spatial tensor in spherical tensor form has typically been partnered with the inverse rotation in Cartesian form to produce equivalent transformations. © 2011 Wiley Periodicals, Inc. Concepts Magn Reson Part A 38: 221–235, 2011.
A randomized trial of internet‐based versus traditional sexual counseling for couples after localized prostate cancer treatment
Authors: Schover Leslie R. , Canada Andrea L. , Yuan Ying , Sui Dawen , Neese Leah , Jenkins Rosell , Rhodes Michelle M.
Published: September 2011

BACKGROUND:

After treatment for prostate cancer, multidisciplinary sexual rehabilitation involving couples appears more promising than traditional urologic treatment for erectile dysfunction (ED). The authors of this report conducted a randomized trial comparing traditional or internet‐based sexual counseling with waitlist (WL) control.

METHODS:

Couples were randomized adaptively to a 3‐month WL, a 3‐session face‐to‐face format (FF), or an internet‐based format (WEB1). A second internet‐based group (WEB2) was added to examine the relation between web site use and outcomes. At baseline, post‐WL, post‐treatment, and 6‐month, and 12‐month follow‐up assessments, participants completed the International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI), the Brief Symptom Inventory‐18 to measure emotional distress, and the abbreviated Dyadic Adjustment Scale.

RESULTS:

Outcomes did not change during the WL period. Of 115 couples that were randomized to FF or WEB1 and 71 couples in the WEB2 group, 34% dropped out. Neither drop‐outs nor improvements in outcomes differed significantly between the 3 treatment groups. In a linear mixed‐model analysis that included all participants, mean ± standard deviation IIEF scores improved significantly across time (baseline, 29.7 ± 17.9; 12 months, 36.2 ± 22.4; P < .001). FSFI scores also improved significantly (baseline, 15.4 ± 8.5; 12 months, 18.2 ± 10.7; P = .034). Better IIEF scores were associated with finding an effective medical treatment for ED and normal female sexual function at baseline. In the WEB2 group, IIEF scores improved significantly more in men who completed >75% of the intervention.

CONCLUSIONS:

An internet‐based sexual counseling program for couples was as effective as a brief, traditional sex therapy format in producing enduring improvements in sexual outcomes after prostate cancer. Cancer 2011;. © 2011 American Cancer Society.
Sunitinib‐induced hyperparathyroidism
Authors: Baldazzi Valentina , Tassi Renato , Lapini Alberto , Lunghi Alice , Garofoli Eleonora , Caruso Salvatore , Carini Marco , Mazzanti Roberto
Published: September 2011

BACKGROUND:

Sunitinib malate is an orally bioavailable tyrosine kinase inhibitor that is active against many tyrosine kinase receptors involving crucial pathways in both healthy tissues and malignant tissues. Because its use in clinical practice is quite recent, many of its possible side effects remain unknown. In this report, the authors describe the incidence of new‐onset hyperparathyroidism in a cohort of patients with metastatic renal cell carcinoma who received treatment with sunitinib.

METHODS:

Twenty‐six patients who received first‐line sunitinib for metastatic renal cell carcinoma were enrolled in this study for a mineral and parathyroid function assessment. Plasma levels of intact parathyroid hormone; serum levels of calcium, phosphorus, 25‐hydroxyvitamin D3, and 1,25‐dihydrovitamin D3; and urinary 24‐hour calcium and phosphorus excretion all were measured in each patient. Biochemical evaluations were performed before the beginning of treatment and at the end of each sunitinib treatment period.

RESULTS:

Eighteen of 26 patients (69.2%) developed hyperparathyroidism with normal serum calcium levels, and 6 of them developed hypophosphatemia. Patients presented with a mean elevation of parathyroid hormone after 2.2 cycles of sunitinib. The levels of 25‐OH vitamin D3 were stable over the course of treatment, whereas 1,25‐OH vitamin D3 levels were increased in 5 hyperparathyroid patients. Those who presenting with elevated parathyroid hormone levels had low or undetectable urinary calcium levels. Parathyroid hormone elevation usually persisted but did not progress during long‐term therapy with sunitinib. Permanent treatment interruption resulted in a resolution of hyperparathyroidism.

CONCLUSIONS:

Hyperparathyroidism developed in an high percentage of patients on sunitinib. Therefore, the authors concluded that sunitinib may affect parathyroid function and bone mineral homeostasis, possibly resulting in abnormal bone remodeling. Cancer 2012;118: 3165–72. © 2011 American Cancer Society.
Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort
Authors: Greenlee Heather , Kwan Marilyn L. , Kushi Lawrence H. , Song Jun , Castillo Adrienne , Weltzien Erin , Quesenberry Charles P. , Caan Bette J.
Published: September 2011

BACKGROUND:

There is concern that antioxidant supplement use during chemotherapy and radiation therapy may decrease treatment effects, yet the effects of such supplements on recurrence and survival are largely unknown.

METHODS:

The authors prospectively examined the associations between antioxidant use after breast cancer (BC) diagnosis and BC outcomes in 2264 women in the Life After Cancer Epidemiology (LACE) cohort. The cohort included women who were diagnosed with early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years postdiagnosis. Baseline data were collected on antioxidant supplement use since diagnosis and other factors. BC recurrence and mortality were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using delayed entry Cox proportional hazards models. All tests of statistical significance were 2‐sided.

RESULTS:

Antioxidant supplement use after diagnosis was reported by 81% of women. Among antioxidant users, frequent use of vitamin C and vitamin E was associated with a decreased risk of BC recurrence (vitamin C: HR, 0.73; 95% CI, 0.55‐0.97; vitamin E: HR, 0.71; 95% CI, 0.54‐0.94); and vitamin E use was associated with a decreased risk of all‐cause mortality (HR, 0.76; 95% CI, 0.58‐1.00). Conversely, frequent use of combination carotenoids was associated with increased risk of death from BC (HR, 2.07; 95% CI, 1.21‐3.56) and all‐cause mortality (HR, 1.75; 95% CI, 1.13‐2.71).

CONCLUSIONS:

Frequent use of vitamin C and vitamin E in the period after BC diagnosis was associated with a decreased likelihood of recurrence, whereas frequent use of combination carotenoids was associated with increased mortality. The effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant. Cancer 2012. © 2011 American Cancer Society.
Phase 2 study of bevacizumab plus erlotinib in patients with advanced hepatocellular cancer
Authors: Philip Philip A. , Mahoney Michelle R. , Holen Kyle D. , Northfelt Donald W. , Pitot Henry C. , Picus Joel , Flynn Patrick J. , Erlichman Charles
Published: September 2011

BACKGROUND:

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are rational targets for therapy in hepatocellular cancer (HCC).

METHODS:

Patients with histologically proven HCC and not amenable to curative or liver directed therapy were included in this 2‐stage phase 2 trial. Eligibility included an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and Child's Pugh score of A or B, and 1 prior systemic therapy. Patients received erlotinib 150 mg daily and bevacizumab 10 mg/kg on days 1 and 15 every 28 days. Objective tumor response was the primary end point.

RESULTS:

Twenty‐seven patients with advanced HCC (median age, 60 years) were enrolled in this multi‐institutional study. The proportion of patients with Child's A classification was 74%. One patient had a confirmed partial response and 11 (48%) achieved stable disease. Median time to disease progression was 3.0 months (95% confidence interval [CI], 1.8‐7.1). Median survival time was 9.5 months (95% CI, 7.1‐17.1). Grade 3 toxicities included rash, hypertension, fatigue, and diarrhea.

CONCLUSIONS:

In this trial, erlotinib combined with bevacizumab had minimal activity in patients with advanced HCC based on objective response and progression‐free survival. The role of targeting EGFR and VEGF in HCC needs further evaluation in molecularly selected patients. Cancer 2012. © 2011 American Cancer Society.
Vector‐valued optimal Lipschitz extensions
Authors: Sheffield Scott , Smart Charles K.
Published: September 2011

Consider a bounded open set
$\font\open=msbm10 at 10pt\def\R{\hbox{\open R}}U \subset \R^n$
and a Lipschitz function $\font\open=msbm10 at 10pt\def\R{\hbox{\open R}}g: \partial U \to \R^m$. Does this function always have a canonical optimal Lipschitz extension to all of U? We propose a notion of optimal Lipschitz extension and address existence and uniqueness in some special cases. In the case n = m = 2, we show that smooth solutions have two phases: in one they are conformal and in the other they are variants of infinity harmonic functions called infinity harmonic fans. We also prove existence and uniqueness for the extension problem on finite graphs. © 2011 Wiley Periodicals, Inc.
From Micro to Macro: Access to Long‐Range Li+ Diffusion Parameters in Solids via Microscopic 6, 7Li Spin‐Alignment Echo NMR Spectroscopy
Authors: Wilkening Martin , Heitjans Paul
Published: September 2011

The development of highly conductive solids is a rapidly growing research area in materials science. In particular, the study of Li‐ion conductors is driven by the ambitious effort to design powerful lithium‐ion batteries. A deeper understanding of Li dynamics in solids requires the availability of a large set of complementary techniques to probe Li self‐diffusion on different length and time‐scales. We report on 7Li as well as 6Li spin‐alignment echo (SAE) nuclear magnetic resonance (NMR) spectroscopy, which is capable of probing long‐range diffusion parameters from a microscopic, that is, atomic‐scale, point of view. So far, variable‐temperature SAE NMR spectroscopy has been applied to a number of polycrystalline and glassy Li‐ion conductors. The materials investigated serve as model systems to unravel the interesting features of the technique in determining reliable Li jump rates and hopping activation energies. In particular, the latter are compared with those probed by macroscopic techniques such as dc‐conductivity measurements that are sensitive to long‐range translational motions.
Noble‐Metal‐Based Catalysts Supported on Zeolites and Macro‐Mesoporous Metal Oxide Supports for the Total Oxidation of Volatile Organic Compounds
Authors: Barakat Tarek , Rooke Joanna C. , Tidahy Haingomalala Lucette , Hosseini Mahsa , Cousin Renaud , Lamonier Jean‐François , Giraudon Jean‐Marc , De Weireld Guy , Su Bao‐Lian , Siffert Stéphane
Published: September 2011

The use of porous materials to eliminate volatile organic compounds (VOCs) has proven very effective towards achieving sustainability and environmental protection goals. The activity of zeolites and macro–mesoporous metal‐oxide supports in the total oxidation of VOCs has been investigated, with and without noble‐metal deposition, to develop highly active catalyst systems where the formation of by‐products was minimal. The first catalysts employed were zeolites, which offered a good activity in the oxidation of VOCs, but were rapidly deactivated by coke deposition. The effects of the acido‐basicity and ionic exchange of these zeolites showed that a higher basicity was related to exchanged ions with lower electronegativities, resulting in better catalytic performances in the elimination of VOCs. Following on from this work, noble metals were deposited onto macro–mesoporous metal‐oxide supports to form mono and bimetallic catalysts. These were then tested in the oxidation of toluene to study their catalytic performance and their deactivation process. PdAu/TiO2 and PdAu/TiO2‐ZrO280/20 catalysts demonstrated the best activity and life span in the oxidation of toluene and propene and offered the lowest temperatures for a 50 % conversion of VOCs and the lowest coke content after catalytic testing. Different characterization techniques were employed to explain the changes occurring in catalyst structure during the oxidation of toluene and propene.
Kikuchi‐fujimoto disease in fine‐needle aspiration smears: A clinico‐cytologic study of 76 cases of KFD and 684 cases of reactive hyperplasia of the lymph node
Authors: Das Dilip K. , Mallik Mrinmay K. , Dashti Hawaraá A.‐H. M. G. H. , Sathar Sitara A. , Jaragh Mohammad , Junaid Thamradin A.
Published: September 2011

Kikuchi‐Fujimoto disease (KFD) is cytologically characterized by a polymorphous lymphoid cell population, abundant karyorrhectic debris and histiocytes, many of which are crescentic (Kikuchi histiocytes). As per reviewed literature, KFD may be confused with tuberculosis, lymphoma, and reactive hyperplasia of lymph nodes (RHLN). Since RHLN was found to be a major challenging factor during routine cytodiagnosis of KFD in our material, we tried to find out the differentiating clinico‐cytologic features between 76 KFD and 684 RHLN cases seen in Kuwait. 63.2% of KFD were in 3rd and 4th decades of life as compared to 40.2% of RHLN (P = 0.0002). Male to female ratio was 1: 2.45 for KFD and 1:1.09 for RHLN (P = 0.0022). Kuwaiti:non‐Kuwaiti ratio was 1:2.04 for KFD and 1.31:1 for RHLN (P < 0.0001). Capillary networks was present in 71.1% of KFD smears and 52.6% of RHLN (P = 0.0023). Tingible body macrophages and dendritic reticulum cells were detected in 17.1% and 22.4%, respectively, in KFD as opposed to 50.1% and 58.8%, respectively, in RHLN (P < 0.0001). Kikuchi histiocyte count ranged from 2 to 36% in KFD and was ≥10% in 31 (40.8%). Rare Kikuchi histiocytes were detected in 16 (2.3%) of RHLN cases but in none of them the count exceeded 1%, whereas their count was >1% in all KFD cases (P < 0.0001). Thus, KFD cases differed significantly from RHLN in respect of age and sex distribution, Kuwaiti:non‐Kuwaiti ratio, and cytomorphologic features such as capillary networks, Kikuchi histiocyte count, dendritic reticulum cells, and tingible body macrophages. Diagn. Cytopathol. 2013;41:288–295. © 2011 Wiley Periodicals, Inc.
The oncocyte that went places: Diagnosis with EUS‐guided FNA
Authors: Safdar Khan Ali , Crowe David R. , Eloubeidi Mohamad A.
Published: September 2011

Although uncommon, Hurthle cell neoplasms have a characteristic histologic and cytologic features which often aid in the diagnosis of these lesions. In fine needle aspiration biopsies, determining malignant potential on cytologic features is challenging unless other evidence of malignancy (such as metastases) are known. The role of EUS‐guided FNA in diagnosing superior mediastinal masses has been described previously. It's role in evaluating subcarinal metastases from lung cancer primaries have also heen studied. However we describe metastatic thyroid Hurthle cell carcinoma to the subcarina diagnosed through EUS‐guided FNA combining the unique cytologic features o Hurthle cell neoplasms and the versatility ofthe endoscopic ultrasound to reach a diagnosis in this unusual neoplasm. Diagn. Cytopathol. 2013;41:977–979. © 2011 Wiley Periodicals, Inc.
High levels of antenatal maternal anxiety are associated with altered cognitive control in five‐year‐old children
Authors: Loomans Eva Margarita , van der Stelt O. , van Eijsden M. , Gemke R. J. B. J. , Vrijkotte T. G. M. , Van den Bergh B. R. H.
Published: September 2011

This longitudinal prospective study examined the relation between maternal anxiety during pregnancy and specific aspects of children's cognitive functioning at age five. Antenatal maternal state‐anxiety was measured around the 16th week of pregnancy. Children's neurocognitive functioning was examined using a simple reaction time (RT) task, and a choice RT task. Multiple regression analyses in the total sample (N = 922) showed that antenatal anxiety was positively related to children's intra‐individual variability in RT in the simple task. In a subsample (n = 100) of women with state‐anxiety scores above the 90th percentile, antenatal anxiety was positively associated with mean RT and intra‐individual variability in RT in the incompatible trials of the choice RT task. In addition, in this subsample of highly anxious mothers we found a significant positive association in boys but not in girls, between prenatal maternal anxiety and intra‐individual variability in RT in the simple task. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:441–450, 2012.