bluuebunny/crossref_metadata_2025 huggingface dataset:
LocaIization of 125l‐labelled α‐r‐atriaI natriuretic peptide in rat tissues by whole‐body and microautoradiography
Authors: TJÄLVE H. , WILANDER E.
Published: December 2008

125I‐labelled α rat atrial natriuretic peptide (28 amino acids: Ser 99‐Tyr 126) ([125I] α‐rANP) was given i.v. to SpragueDawley rats and the distribution of radioactivity in the tissues was examined by whole‐body and microautoradiography at intervals from 2 min to 4 h after the administration. Inhibition of uptake of the [1251]α‐rANP by simultaneous injection of an excess of non‐labelled α‐rANP was taken as an indication that highly labelled structures in rats injected with [125I]α(‐rANP alone are due to an abundance of specific receptors for the peptide. In the rats given only the [125I]α‐rANP a rapid and high radioactivity occurred in the renal glomeruli, the endocardium of the heart ventricles, the endothelium of the processus ciliares of the eyes, the portal vessels and a few larger vessels of the liver, the subcapsular vessels of the adrenal glands and the parenchyma of the lungs. Other tissues showing a distinct, but less prominent, radioactivity were the endocardium of the heart atria, the walls of the great afferent and efferent vessels in the thoracic cavity, the choroid plexuses of the brain ventricles, the pia mater, brown fat, the muscularis layer of the stomach and the intestines, the lamina propria of the villi in the small intestine and the walls of a few small blood vessels in the kidney medulla. The specific labelling was highest at 2 min after injectian and then diminished at later intervals.

Several of the labelled structures are localized in tissues involved in the regulation of blood pressure, and fluid and electrolyte homeostasis, processes in which the atrial peptides are considered to play a role. It is suggested that high concentrations of receptors are present at the sites at which the [125I]α‐rANP was strongly localized and that biological effects of the atrial peptides are everted via these structres.
Evidence that an L‐fucose‐containing component in the β‐cellplasma membrane is involved in the regulation of glucose‐induced insulin release
Authors: SANDSTRÖM P.‐E. , SEHLIN J.
Published: December 2008

The effect of the L‐fucose‐selective lectin Ulex Europeus I (UEA I), a blocker of the Na+, K+, CIF co‐transport system in the kidney, was tested on insulin secretion from isolated β‐cell‐rich pancreatic islets. UEA I at doses from 50 to 100 μgml‐1significantly reduced the glucose‐induced (20 mmol l‐1) insulin release whereas the basal (3 mmol l‐1) release was unaffected. The inhibitory effect of 100 μgml‐1UEA I was completely abolished by 10 mmol 1‐lL‐fucose. The data suggest that an I ‐fucose‐containing structure in the β‐cell plasma membrane participates in the regulation of glucose‐induced insulin release. This structure may be similar to the L‐fucose‐containing glycoprotein in the kidney tubules that is believed to be the Na+, K+, Cl‐co‐transporter.
A vaccine manufacturer’s approach to address medical needs related to seasonal and pandemic influenza viruses
Authors: Baras Benoit , Bouveret Nancy , Devaster Jeanne‐Marie , Fries Louis , Gillard Paul , Sänger Roland , Hanon Emmanuel
Published: December 2008

Abstract Vaccination is considered to be one of the most effective tools to decrease morbidity as well as mortality caused by influenza viruses.

For the prevention of seasonal influenza, Fluarix™ and FluLaval™ have been marketed since 1987 and 1992, respectively. Both vaccines have consistently been shown to meet or exceed the regulatory criteria for immunogenicity against the three strains H1N1, H3N2 and B, have a good safety profile, and are recommended for vaccinating children and adults of all ages.

For the prevention of pandemic influenza, GlaxoSmithKline (GSK) has obtained licensure of a pre‐pandemic vaccine, Prepandrix™. This split‐virus H5N1 adjuvanted with AS03, a proprietary oil‐in‐water emulsion‐based adjuvant system, has demonstrated broad immunity against drifted H5N1 strains and has been shown to be effective in preventing mortality and viral shedding in animal studies.

The influenza vaccine portfolio of GSK addresses specific medical needs related to seasonal or pandemic influenza viruses, which remain an important public health threat worldwide.
Yearly licensing studies from 1997 to 2007 of the inactivated whole virus seasonal influenza vaccine fluval – a useful approach to pandemic vaccine development even in less well developed countries?
Authors: Vajo Zoltan , Kosa Lajos , Szilvasy Istvan , Pauliny Zsuzsanna , Bartha Kálmán , Visontay Ildiko , Jankovics Mate , Kis Agnes , Jankovics Istvan
Published: December 2008

Objective  Seasonal vaccination has been consistently shown to significantly reduce morbidity and mortality because of influenza epidemics, even in healthy, working adults. Here we report the results of the yearly licensing studies of the past 11 influenza seasons (1997–2007) with a trivalent, inactivated whole virus vaccine with an aluminum phosphate adjuvant system.

Methods  Sixty healthy volunteers per age group (18–60 years and 60 years and older) were enrolled to receive vaccination each year, thus, a total of 1080 subjects were studied. Serum antibody titers were measured by hemagglutination inhibition (HI).

Results:  The vaccine met the criteria for licensing each year, meaning seroprotection (achievement of an HI titer of >1:40 in >70% of subjects); seroconversion, i.e. a >4‐fold increase in HI antibody titer, or reaching a titer of >1:40, in >40% of subjects; and an increase in geometric mean titers by >2·5‐fold. Side effects were rare and mild. The same method was used to produce a pre‐pandemic vaccine against influenza A (H5N1), which has been shown to be safe and immunogenic in humans.

Conclusions  We conclude that the method presented is safe, effective and may serve as a useful approach to seasonal and pandemic vaccine production even in less well‐developed countries by means of technological transfer.
MF59®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis
Authors: Banzhoff Angelika , Pellegrini Michele , Del Giudice Giuseppe , Fragapane Elena , Groth Nicola , Podda Audino
Published: December 2008

Abstract  Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross‐reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non‐adjuvanted pre‐pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre‐pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross‐reactive immunogenicity. MF59®, the first oil‐in‐water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59‐adjuvanted seasonal influenza vaccine (Fluad®) has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non‐adjuvanted vaccines, and to provide cross‐reactive immunity against divergent influenza strains. Similar results have been generated with a MF59‐adjuvanted H5N1 pre‐pandemic vaccine, which showed higher and broader immunogenicity compared with non‐adjuvanted pre‐pandemic vaccines.
Improving seasonal and pandemic influenza vaccines
Authors: Saville Melanie , Marsh Grenville , Hoffenbach Agnes
Published: December 2008

Abstract  Challenges facing seasonal and pandemic influenza vaccination include: increasing the immunogenicity of seasonal vaccines for the most vulnerable, increasing vaccination coverage against seasonal influenza, and developing vaccines against pandemic strains that are immunogenic with very low quantities of antigen to maximize the number of people who can be vaccinated with a finite production capacity. We review Sanofi Pasteur’s epidemic and pandemic influenza research and development programmes with emphasis on two key projects: intradermal influenza vaccine for seasonal vaccination of both elderly and younger adults, and pandemic influenza vaccine.
Safety and immunogenicity of live attenuated influenza reassortant H5 vaccine (phase I–II clinical trials)
Authors: Rudenko Larisa , Desheva Julia , Korovkin Sergey , Mironov Alexander , Rekstin Andrey , Grigorieva Elena , Donina Svetlana , Gambaryan Alexandra , Katlinsky Anton
Published: December 2008

Objective Our studies aimed to evaluate in clinical trials the safety and immunogenicity of an H5 live influenza vaccine candidate obtained using classical reassortment techniques from a low pathogenicity avian influenza (LPAI) A/Duck/Potsdam/1402‐6/86(H5N2) virus and the cold‐adapted (ca) donor strain A/Leningrad/134/17/57(H2N2).

Methods During Phase I–II clinical trials, volunteers received intranasally two doses of reassortant influenza vaccine strain A/17/Duck/Potsdam/86/92 (H5N2) 21 days apart. Clinical examination of all vaccinees was conducted 7 days post‐vaccination. Serum antibody responses were measured by hemagglutination‐inhibition and microneutralization and local antibodies were estimated using an enzyme‐linked immunosorbent assay test.

Results The vaccine was safe and of low reactogenicity with no febrile reactions. After revaccination 47·1–54·8% of subjects showed ≥fourfold seroconversions of Hamagglutination inhibition (HAI) antibodies to the hemagglutinin (HA) antigen of the A/17/Duck/Potsdam/86/92 (H5N2) virus and 29·4–30·8% were seroconverted to the HA antigen of the reverse genetics reassortant A/Indonesia/05/2005 × PR8 IBCDC‐RG (H5N1). Virus‐neutralizing antibody levels in sera of volunteers were similar to those shown in HAI test. The virus‐specific nasal IgA antibody response after two vaccine doses demonstrated significant increases of ≥fourfold rise SIgA antibodies (65%) geometrical mean titers (16·0) and a rise in SIgA antibodies (2·8) compared with one dose.

Conclusion The live attenuated influenza vaccine candidate prepared using the LPAI A(H5N2) strain was well tolerated and elicited serum and local immune responses. There was evident cross‐reactivity to the A(H5N1) strain in the HAI test.
Safety and immunogenicity of Sinovac’s prototype pandemic influenza H5N1 vaccines: a review on clinical trials
Authors: Qiu Yuan‐Zheng , Yin Wei‐Dong
Published: December 2008

Abstract  Sinovac Biotech started to develop prototype pandemic influenza H5N1 vaccines in March 2004. On 2 April 2008, Sinovac’s inactivated, aluminium‐adjuvanted, whole‐virion prototype pandemic influenza A (H5N1) vaccine (PanFlu™) was granted production licensure by the China regulatory authority State Food and Drug Administration. The whole‐virion H5N1 vaccine was manufactured in embryonated hens’ eggs using the reassortant strain NIBRG‐14 (A/Vietnam/1194/2004‐A/PR/8/34) as vaccine virus. It showed good safety, immunogenicity and cross‐reactivity in immunologically naïve adults. In primed adults, the vaccine induced a strong booster response. Plasma from a vaccinated individual showed a beneficial effect following passive immunotherapy of an H5N1 human infection case. This article reviews the process, status and results of clinical evaluation of Sinovac’s whole‐ and split‐virion H5N1 vaccines by focusing on the whole‐virion vaccine.
The extent of emphysema in patients with COPD
Authors: Shaker Saher Burhan , Stavngaard Trine , Hestad Marianne , Bach Karen Skjoelstrup , Tonnesen Philip , Dirksen Asger
Published: December 2008

Background and Aims:  The global initiative for COPD (GOLD) adopted the degree of airway obstruction as a measure of the severity of the disease. The objective of this study was to apply CT to assess the extent of emphysema in patients with chronic obstructive pulmonary disease (COPD) and relate this extent to the GOLD stage of airway obstruction.

Materials and Methods:  We included 209 patients with COPD. COPD was defined as FEV1/FVC < 0.70 and no reversibility to β2‐agonists. All patients were current smokers with a smoking history of ≥20 pack‐years. Patients were assessed by lung function measurement and visual and quantitative assessment of CT, from which the relative area of emphysema below −910 Hounsfield units (RA‐910) was extracted.

Results:  Mean RA‐910 was 7.4% (n = 5) in patients with GOLD stage I, 17.0% (n = 119) in stage II, 24.2% (n = 79) in stage III and 33.9% (n = 6) in stage IV. Regression analysis showed a change in RA‐910 of 7.8% with increasing severity according to GOLD stage (P < 0.001). Combined visual and quantitative assessment of CT showed that 184 patients had radiological evidence of emphysema, whereas 25 patients had no emphysema.

Conclusion:  The extent of emphysema increases with increasing severity of COPD and most patients with COPD have emphysema. Tissue destruction by emphysema is therefore an important determinant of disease severity in COPD.

Please cite this paper as: Shaker SB, Stavngaard T, Hestad M, Bach KS, Tonnesen P and Dirksen A. The extent of emphysema in patients with COPD. The Clinical Respiratory Journal 2009; 3: 15–21.
Overview on the current status of asthma genetics
Authors: Halapi Eva , Bjornsdottir Unnur Steina
Published: December 2008

Introduction:  Asthma is a complex heterogeneous and mutifactorial disease occurring at the interface of multiple genes that interact with various environmental stimuli insulting the immune system at different levels and different times of disease susceptibility.

Objective:  The present paper is a review of the current status of the genetics of asthma.

Results:  Sequence variants in hundreds of genes have been associated with asthma using both family‐based and case control screening methods.

Conclusion:  As the number of genes known to be associated with asthma risk is rapidly growing, it is essential to begin integrating epidemiologic, genetic and genomic strategies to unravel the relationships between genotype and phenotype, and elucidate the pathogenesis of asthma with the goal to make clinical use of these discoveries.

Please cite this paper as: Halapi E and Bjornsdottir US. Overview on the current status of asthma genetics. The Clinical Respiratory Journal 2009; 3: 2–7.
Strain‐specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred mice
Authors: Neal Kathleen B. , Parry Laura J. , Bornstein Joel C.
Published: December 2008

Serotonin (5‐HT) powerfully affects small intestinal motility and 5‐HT‐immunoreactive (IR) neurones are highly conserved between species. 5‐HT synthesis in central neurones and gastrointestinal mucosa depends on tissue‐specific isoforms of the enzyme tryptophan hydroxylase (TPH). RT‐PCR identified strain‐specific expression of a polymorphism (1473C/G) of thetph2gene in longitudinal muscle–myenteric plexus preparations of C57Bl/6 and Balb/c mice. The former expressed the high‐activity C allele, the latter the low‐activity G allele. Confocal microscopy was used to examine close contacts between 5‐HT‐IR varicosities and myenteric neurones immunoreactive for neuronal nitric oxide synthase (NOS) or calretinin in these two strains. Significantly more close contacts were identified to NOS‐ (P< 0.05) and calretinin‐IR (P< 0.01) neurones in C57Bl/6 jejunum (NOS 1.6 ± 0.3,n= 52; calretinin 5.2 ± 0.4,n= 54), than Balb/c jejunum (NOS 0.9 ± 0.2,n= 78; calretinin 3.5 ± 0.3,n= 98). Propagating contractile complexes (PCCs) were identified in the isolated jejunum by constructing spatiotemporal maps from video recordings of cannulated segmentsin vitro. These clusters of contractions usually arose towards the anal end and propagated orally. Regular PCCs were initiated at intraluminal pressures of 6 cmH2O, and abolished by tetrodotoxin (1 μm). Jejunal PCCs from C57Bl/6 mice were suppressed by a combination of granisetron (1 μm, 5‐HT3antagonist) and SB207266 (10 nm, 5‐HT4antagonist), but PCCs from Balb/c mice were unaffected. There were, however, no strain‐specific differences in sensitivity of longitudinal muscle contractions to exogenous 5‐HT or blockade of 5‐HT3and 5‐HT4receptors. These data associate a genetic difference with significant structural and functional consequences for enteric neural serotonergic pathways in the jejunum.
Fluorescence Resonance Energy Transfer-Based Assay for Characterization of Hepatitis C Virus NS3-4A Protease Activity in Live Cells
Authors: Sabariegos Rosario , Picazo Fernando , Domingo Beatriz , Franco Sandra , Martinez Miguel-Angel , Llopis Juan
Published: December 2008

The NS3/4A protease from hepatitis C virus (HCV) plays a key role in viral replication. We report a system for monitoring the activity of this enzyme in single living mammalian cells. We constructed a fluorescence resonance energy transfer (FRET) probe that consists of an enhanced cyan fluorescent protein-citrine fusion, with a cleavage site for HCV NS3/4A protease embedded within the linker between them. Expression of the biosensor in mammalian cells resulted in a FRET signal, and cotransfection with the NS3/4A expression vector produced a significant reduction in FRET, indicating that the cleavage site was processed. Western blot and spectrofluorimetry analysis confirmed the physical cleavage of the fusion probe by the NS3/4A protease. As the level of FRET decay was a function of the protease activity, the system allowed testing of NS3/4A protease variants with different catalytic efficiencies. This FRET probe could be adapted for high-throughput screening of new HCV NS3/4 protease inhibitors.
Nucleoside and Nucleotide Analogs Select in Culture for Different Patterns of Drug Resistance in Human Immunodeficiency Virus Types 1 and 2
Authors: Ntemgwa Michel L. , Toni Thomas d'Aquin , Brenner Bluma G. , Oliveira Maureen , Asahchop Eugene L. , Moisi Daniela , Wainberg Mark A.
Published: December 2008

Recent findings suggest bidirectional antagonisms between the K65R mutation and thymidine analogue mutations in human immunodeficiency virus type 1 (HIV-1)-infected, treatment-experienced patients, yet little is known about HIV-2 in this regard. This study addressed the effects of innate polymorphisms in HIV-2 on emergent resistance to nucleoside/nucleotide analogues. Emergent drug resistance profiles in HIV-2 subtypes A (n= 3) and B (n= 1) were compared to those of HIV-1 subtypes B and C. Drug resistance was evaluated with cord blood mononuclear cells (CBMCs) and MT2 cells, using selective pressure with tenofovir (TFV), zidovudine (ZDV), stavudine (d4T), didanosine (ddI), abacavir (ABC), lamivudine (3TC), emtricitabine (FTC), or various dual-drug combinations. Resistance was evaluated using conventional and ultrasensitive sequencing approaches. In agreement with our previous findings, dual-drug combinations of TFV, ddI, ABC, d4T, ZDV, and 3TC preferentially selected for K65R in HIV-1 subtype C isolates. In HIV-1 subtype B, TFV-3TC and ZDV-3TC selected for M184I and D67N, respectively. In contrast, selections with all four HIV-2 cultures favored the development of M184I in dual-drug combinations that included either 3TC or FTC. Since HIV-2 cultures did not develop K65R, an ultrasensitive allele-specific real-time PCR assay was developed to distinguish the presence of 65R from wild-type K65 after 16 cycles with a discriminatory ability of 0.1% against a population of wild-type virus. These results underscore potential differences in emergent drug resistance pathways in HIV-1 and HIV-2 and show that polymorphisms may influence the development of the resistance pathways that are likely to emerge.
Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant Δ
ureC hly
+
Mycobacterium bovis
BCG and Modified Vaccinia Virus Ankara Expressing
M. tuberculosis
Antigen 85A against Murine Tuberculosis
Authors: Tchilian Elma Z. , Desel Christiane , Forbes Emily K. , Bandermann Silke , Sander Clare R. , Hill Adrian V. S. , McShane Helen , Kaufmann Stefan H. E.
Published: December 2008

In the light of the recent emergence of multidrug-resistant and extensively drug-resistant strains of
Mycobacterium tuberculosis
, the epidemic of tuberculosis (TB) in populations coinfected with human immunodeficiency virus, and the failure of
Mycobacterium bovis
bacillus Calmette-Guerin (BCG) to protect against disease, new vaccines against TB are urgently needed. Two promising new vaccine candidates are the recombinant Δ
ureC hly
+
BCG (recBCG), which has been developed to replace the current BCG vaccine strain, and modified vaccinia virus Ankara (MVA) expressing
M. tuberculosis
antigen 85A (MVA85A), which is a leading candidate vaccine designed to boost the protective efficacy of BCG. In the present study, we examined the effect of MVA85A boosting on the protection afforded at 12 weeks postchallenge by BCG and recBCG by using bacterial CFU as an efficacy readout. recBCG-immunized mice were significantly better protected against aerosol challenge with
M. tuberculosis
than mice immunized with the parental strain of BCG. Intradermal boosting with MVA85A did not reduce the bacterial burden any further. In order to identify a marker for the development of a protective immune response against
M. tuberculosis
challenge, we analyzed splenocytes after priming or prime-boosting by using intracytoplasmic cytokine staining and assays for cytokine secretion. Boosting with MVA85A, but not priming with BCG or recBCG, greatly increased the antigen 85A-specific T-cell response, suggesting that the mechanism of protection may differ from that against BCG or recBCG. We show that the numbers of systemic multifunctional cytokine-producing cells did not correlate with protection against aerosol challenge in BALB/c mice. This emphasizes the need for new biomarkers for the evaluation of TB vaccine efficacy.
Plant community diversity and composition provide little resistance to Juniperus encroachment
Authors: Ganguli Amy C. , Engle David M. , Mayer Paul M. , Hellgren Eric C.
Published: December 2008

Widespread encroachment of the fire-intolerant species Juniperus virginiana  L. into North American grasslands and savannahs where fire has largely been removed has prompted the need to identify mechanisms driving J. virginiana encroachment. We tested whether encroachment success of J. virginiana is related to plant species diversity and composition across three plant communities. We predicted J. virginiana encroachment success would (i) decrease with increasing diversity, and (ii) J. virginiana encroachment success would be unrelated to species composition. We simulated encroachment by planting J. virginiana seedlings in tallgrass prairie, old-field grassland, and upland oak forest. We used J. virginiana survival and growth as an index of encroachment success and evaluated success as a function of plant community traits (i.e., species richness, species diversity, and species composition). Our results indicated that J. virginiana encroachment success increased with increasing plant richness and diversity. Moreover, growth and survival of J. virginiana seedlings was associated with plant species composition only in the old-field grassland and upland oak forest. These results suggest that greater plant species richness and diversity provide little resistance to J. virginiana encroachment, and the results suggest resource availability and other biotic or abiotic factors are determinants of J. virginiana encroachment success.
Compositional, cover, and diversity changes after prescribed fire in a mature eastern white pine forest
Authors: Cook James E. , Jensen Nicholas , Galbraith Betsy
Published: December 2008

Eastern white pine ( Pinus strobus L.) forests are considered fire dependent, but little is known about the role of low-intensity fires. We conducted four prescribed burns to examine understory effects. The vegetation was sampled one year before and two consecutive years after the burns. Understory metrics were calculated for the vernal (May–June) and aestival (mid-August) assemblages. The fires resulted in a cumulative mortality rate in the sapling layer of 64%. During the first year, the burns had a neutral or repressive effect on the understory. However, cover, richness, and species density increased significantly for both assemblages during the second year; however, the relative change was greater for the vernal assemblage. The fires also led to greater compositional turnover than in the controls. The large increases in late-season cover were primarily from reduced competition and enhanced regeneration. The fires created a brief window of invasion opportunity, which was minimally captured by annuals and exotics. Ordination indicated different short-term successional pathways for the vernal (diverging) and aestival (converging) assemblages. This difference by time period was consistent with similarity measures. The study suggests that low intensity fires play a vital role in understory diversity and structure in white pine forests.
Numerical analysis of two-dimensional flow in an AC magneto-hydrodynamic micropump
Authors: Abdullah M , Duwairi H
Published: December 2008

The effect of a fluctuating Lorentz force on the AC magnetohydrodynamic micropump is studied. A two-dimensional transient developing laminar flow is modeled. The governing Navier-Stokes equations are solved numerically using the finite-difference method and the SIMPLE algorithm. The effect of the Hartmann number on the transient and steady-flow velocity is studied. It is found that controlling the electrical conductivity and magnetic-flux density will allow us to control the entrance region length. The effect of the Stanton number and phase angle is also included, and it is found that at high frequency, the pulsed volume is small, which yields a continuous flow instead of a pulsating flow, and the magnitude and direction of the flow can be controlled by the phase shift between the electrical and magnetic fields.PACS Nos.: 45.20.dh, 47.10.dh, 47.11.dc, 47.15.Cb
DFT mechanistic studies on the epoxidation of cyclohexene by non-heme tetraaza manganese complexes
Authors: Haras Alicja , Ziegler Tom
Published: December 2008

Herein, we report density functional calculations on the epoxidation of cyclohexene with H2O2 activated by (Me2EBC)MnCl2 (Me2EBC stands for 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane). The computed energy landscapes for different interaction modes of cyclohexene with the MnIV-hydroperoxo complex and the MnV-oxo species support recent experimental findings by Busch and co-workers [J. Am. Chem. Soc. 127, 17170 (2005)], according to which the MnIV-hydroperoxo species is the active complex for olefin epoxidation. Thus, the dominant olefin epoxidation pathway is via direct transfer of the distal protonated oxygen of the hydroperoxo adduct without changes in the oxydation state of its tetravalent metal centre, i.e., the mechanism commonly observed in the uncatalyzed epoxidation by peracids. The homolytic decomposition of the O–OH bond in the active manganese complex leading to the MnV-oxo species is found to be the only epoxidation pathway that could possibly compete with the Oβ transfer from the hydroperoxo adduct. However, the generated MnV-oxo is shown to be a rather poor oxidant resulting in low yields of the target epoxy cyclohexane.Key words: epoxidation, density functional theory, permanganic acid, peracid.
Gold complexes of ditelluridoimidodiphosphinate ligands — Reversible oxidation of Au(I) to Au(III) via insertion of gold into a phosphorus–tellurium bond
Authors: Eisler Dana J , Robertson Stuart D , Chivers Tristram
Published: December 2008

The reaction of (THT)AuCl with (TMEDA)Na[N(TePR2)2] (R = Ph, i-Pr, t-Bu) produces a series of gold (III) complexes of the type [{R2PNP(Te)R2}Au(µ-Te)]2(4a, R = i-Pr; 4b, R = Ph; 4c, R = t-Bu) rather than the expected homoleptic Au(I) complexes of the ditelluridoimidodiphosphinate ligands. A combination of solution- and solid-state NMR studies shows that both cis and trans isomers of 4a–4c are formed in these reactions. X-ray structural determinations of the trans isomers of 4a–4c reveal a centrosymmetric arrangement with a central four-membered Au2Te2ring formed by the formal insertion of gold into a P–Te bond; this insertion process was shown to be reversible upon addition of PPh3to 4a to give the monomeric gold(I) complex Ph3PAu[N{TeP(i-Pr)2}2]. The X-ray structure of cis-4b is also described.Key words: gold, tellurium, redox, X-ray structures, imidodiphosphinate.
A DFT investigation into the origin of regioselectivity in palladium-catalyzed allylic amination
Authors: Iuliis Marco Zimmer De , Watson Iain DG , Yudin Andrei K , Morris Robert H
Published: December 2008

The addition of amines or aziridines to prenylacetate is catalyzed by palladium phosphine complexes. The first-formed products have recently been shown to be the branched olefins R2NCMe2CH=CH2, R = alkyl, or R2 = 1,2-C6H10, for example. DFT calculations using the MPW1K functional were performed on reactions of the suspected intermediate η3-prenyl complex [Pd(η3-Me2CCHCH2)(PH3)2]+ with dimethylamine and ethylene imine. The activation barrier for the nucleophilic attack by the amine or the aziridine is calculated to be similar for either the sterically hindered site of the π-allyl ligand to produce the branched olefin complex or the unhindered site to give the linear olefin complex. Therefore, these calculations do not reveal the experimentally observed preference for attack. This observation, along with the experimental observation of lack of isomerization of the branched olefin product of the aziridine reactions, appears to rule out the intermediacy of a π-allyl complex [Pd(η3-Me2CCHCH2)L2]+, L = phosphine or L2 = diphosphine in the C–N bond-forming reaction.Key words: allyl palladium, amine, aziridine, DFT, mechanism, catalysis.
Synthesis of platinum(II) cyclometallated compounds derived from imines containing pyridyl or pyrimidyl groups
Authors: Crespo Margarita , Anderson Craig M , Tanski Joseph M
Published: December 2008

The reaction of compounds [Pt2Me4(µ-SMe2)2] and cis-[PtPh2(SMe2)2] with ligands 4-(2′-C5H4N)C6H4CHN CH2CH2NMe2(1a) and 4-(3′,5′-C4H3N2)C6H4CHNCH2CH2NMe2(1b) carried out in acetone at room temperature produced compounds in which the imines act as bidentate [N,N′] ligands. Analogous compounds could be obtained in refluxing methanol when cis-[PtCl2(DMSO)2] was used as starting material. The corresponding cyclometallation processes leading to platinum(II) compounds with a tridentate [C,N,N′] ligand took place under different reaction conditions, except for metallation of 1a with cis-[PtPh2(SMe2)2], which could not be achieved. All compounds were characterized by usual techniques and [PtMe{4-(3′,5′-C4H3N2)C6H3CHNCH2CH2NMe2}] (3bMe) was also characterized crystallographically.Key words: platinum, imines, pyridyl, pyrimidyl, cyclometallation, crystal structure.
A weakly coordinating anion as a tripodal “Br3”-ligand for platinum(IV) — Structure of [(closo-CB11H6Br6)PtMe3]
Authors: De Crisci Antonio G , Kleingardner Jesse , Lough Alan J , Larsen Anna , Fekl Ulrich
Published: December 2008

Synthesis, structure, and NMR spectroscopic data for [(closo-CB11H6Br6)PtMe3] are reported. This neutral platinum(IV) complex contains the closo-CB11H6Br6–anion bonded to the trimethylplatinum(IV) cation via three boron-bound bromines. Closo-CB11H6Br6–, which often acts as weakly coordinating or even non-coordinating anion, adopts here a role still very rare for this anion: it acts as a tripodal capping ligand enabling a pseudo-octahedral geometry at a d6metal center. Three bromines from the lower hemisphere of the hexahalogenated carboranate coordinate to Pt(IV), and distortions from ideal octahedral angles at Pt are marginal (<3°). Pt-Br bond lengths are 2.7279(18), 2.7129(17), and 2.7671(18) Å. Using the2JPtHcoupling constant of Pt-bonded methyl groups (79.0 Hz) as indicator of the donor strength of the tripodal cap, the prediction is obtained that closo-CB11H6Br6–is a relatively weak donor toward the trimethylplatinum(IV) cation. Ligand competition equilibria can be expected to depend on both the intrinsic donor strengths of competing ligands and on the effects of charge and geometry. We observe that closo-CB11H6Br6–is capable of replacing acetone from Me3Pt(acetone)3+, whereas BF4–counterion is unable to replace acetone under similar conditions.Key words: non-coordinating anion, platinum(IV), trimethyl, closo-carboranate, tripodal, trans-influence, NMR spectroscopy.
Self-assembly in Schiff base lanthanide complexes — From supramolecular dimers to coordination polymers
Authors: Radecka-Paryzek Wanda
Published: December 2008

A review is given of the latest contribution of the author’s research group to the coordination chemistry of Schiff base polyaza macrocycles and acyclic salicylaldimines. Focus is placed on the effectiveness of lanthanides in supramolecular self-assembly of the components leading to the formation of compounds with unusual properties and structures.Key words: Schiff base macrocycles, salicylaldimines, lanthanides, self-assembly, template synthesis.
Ferrocenyl phosphine–oxazaphospholidine oxide ligands for the Suzuki–Miyaura coupling of hindered aryl bromides and chlorides
Authors: Vinci Daniele , Martins Nelson , Saidi Ourida , Bacsa John , Brigas Amadeu , Xiao Jianliang
Published: December 2008

A series of ferrocenyl oxazaphospholidine phosphines that differ electronically and sterically were investigated as ligands for the Suzuki–Miyaura cross-coupling reactions. One of these compounds, 1, was shown to be highly effective in the coupling reactions of bulky aryl bromides with boronic acids when combined with Pd(OAc)2, while another, 2, was capable of coupling aryl chlorides with boronic acids. However, these ligands were less effective in asymmetric induction.Key words: Suzuki–Miyaura coupling, ferrocenyl phosphines, aryl bromides, aryl chlorides, palladium.
Reactivity of IrCl(PPh3)3 with diphenylacetylene — A direct route to 1-iridaindene
Authors: Choudhury Joyanta , Pratihar Sanjay , Maity Arnab Kumar , Roy Sujit
Published: December 2008

The 1-iridaindene complex, Ir[C8H5(Ph-2)]Cl(PPh3)2 (2), has been prepared from the reaction of IrCl(PPh3)3 with PhC≡CPh by a novel direct cycloiridation reaction. A plausible mechanistic pathway has been suggested involving π-coordination assisted ortho- C–H activation and subsequent alkyne hydroiridation reaction to provide the five-member iridacycle.Key words: iridium, diphenylacetylene, C–H activation, cyclometallation, metallacycle.
Tungsten coordination chemistry of 1,4-bisdiphenylphosphinobutadiyne — Synthesis of coordination macrocycles and factors controlling diyne cycloaddition
Authors: Tsui Jordan A , Bolton Timothy M , Sterenberg Brian T
Published: December 2008

The 1:1 reaction of [W(CO)4(2-picoline)2] (1) with Ph2PCtriple bondC-Ctriple bondCPPh2 (2) led to {[cis-W(CO)4]2(µ-Ph2PC4PPh2)2} (3), in which two bis(diphenylphosphino)butadiyne ligands bridge two tetracarbonyltungsten centres. Reaction of 1 with excess 2 led to [cis-W(CO)4(Ph2PC4PPh2-κ1-P)2] (4), in which two dangling bis-phosphines are coordinated to one metal centre, and reaction of 2 with two equivalents of 1 led to {[W(2-picoline)(CO)4]2(µ-Ph2PC4PPh2)} (5), in which one ligand bridges two tungsten centres. Combination of 4 and 5 led to the trimeric complex {[cis-W(CO)4]3(µ-Ph2PC4PPh2)3} (6), in which three tetracarbonyltungsten centres are bridged by three bisdiphenylphosphinobutadiyne ligands. The dimeric complex 3 showed no reactivity towards alkyne cycloaddition; however, the trimeric complex 6 undergoes cycloaddition at moderate temperatures to form {[W(CO)4]3[µ3-C12(Ph2P)6]} (8), which contains a cyclododecatrienetriyene ring. Comparison of structural data for the template complexes 3 and 6, as well that of previously described platinum template complexes, suggests that alkyne cycloaddition reactions are favoured by proximity of the alkynyl carbons α to phosphorus in adjacent ligands.Key words: coordination chemistry, diyne, cycloaddition, templated reaction, tungsten.
Formation of a [2]rotaxane and [2]catenane based on PdBr2L2 as a template
Authors: Blight Barry A , Wisner James A , Jennings Michael C
Published: December 2008

Previous studies have determined that neutral palladium(II) dibromide complexes template the formation of [2]pseudorotaxanes, albeit with weaker affinities than the analogous palladium(II) dichloride species. Here, the self-assembly of both [2]rotaxane (2) and [2]catenane (5) were attempted using a PdBr2L2 centre as the template, resulting in the desired interlocked structures. The structures were confirmed by NMR spectroscopy, CSI-MS, and single crystal X-ray diffraction analyses. [2]Rotaxane 2 was isolated in 53% and [2]catenane 5 in 41% yields. The lower yields observed in comparison to the chloride analogues can be attributed to the reduced template effect of the palladium(II) dibromide subunits, caused by both the poor steric fit of the bromides in the isophthalamide cleft and bromide’s reduced capacity as a hydrogen bond acceptor.Key words: rotaxane, catenane, hydrogen bonding, interlocked, supramolecular chemistry.
A microporous alkaline-earth phosphonate sustained by one-dimensional inorganic and organic units
Authors: Vaidhyanathan Ramanathan , Mahmoudkhani Amir H , Shimizu George KH
Published: December 2008

The single-crystal X-ray structure of a microporous alkaline-earth phosphonate incorporating a new triphosphonate ligand is presented. Sr2(H2L)(CH3OH)(H2O)4, where L = 1,3,5-tris(4-phosphonophenyl)benzene, crystallizes in triclinic space group P-1 (a = 6.9230(4) Å, b = 15.3370(9) Å, c = 16.1930(11) Å, α = 62.201(3)°, β = 85.288(4)°, γ = 86.665(4)°). The solid is sustained by cooperative interactions between both one-dimensional inorganic and organic columns and forms a two-fold interpenetrated microporous structure. Gas and vapour sorption experiments confirm the microporosity. Based upon the sustaining interactions, this compound can serve as a model for more porous structures as extension of its structure disfavours further interpenetration.Key words: metal–organic framework, coordination polymer, phosphonate, microporous, alkaline earth.
Synthesis and evaluation of the in vitro DNA-binding properties of chiralcis-dichloro(pyridyloxazoline)platinum(II) complexes
Authors: Dodd David W , Toews Heather E , Trevail Michael J , Jennings Michael C , Hudson Robert HE , Jones Nathan D
Published: December 2008

A series of chiral cis-dichloro(pyridyloxazoline)platinum(II) and palladium(II) complexes were synthesized and their reactivity towards a defined sequence of single-stranded and double-stranded DNA was investigated in comparison to cisplatin. The compounds differed in the nature and absolute configuration of the substituent at the C4 position of the oxazoline ring. The DNA-binding ability of these compounds was evaluated by HPLC analysis, post metal exposure, of enzymatic digests of an undecamer duplex containing one putative metallation site. Polyacrylamide gel electrophoresis (PAGE) and thermal denaturation confirmed the results of the HPLC analysis, which showed that the stereochemistry and character of the substituent at the C4 position of the oxazoline ring had little effect on DNA binding, possibly due to the formation of monofunctional adducts.Key words: cisplatin, chiral, pyridyloxazoline, DNA-binding studies, platinum, palladium.
Mechanistic investigations of bipyrimidine-promoted palladium-catalyzed allylic acetoxylation of olefins
Authors: Lin Bo-Lin , Labinger Jay A , Bercaw John E
Published: December 2008

Several pyridine-like ligands were found to improve Pd(OAc)2-catalyzed allylic oxidation of allylbenzene to cinnamyl acetate by p-benzoquinone in acetic acid. The best ligand examined, bipyrimidine, was used to identify the catalyst precursor for this system, (bipyrimidine)Pd(OAc)2, which was fully characterized. Mechanistic studies suggest the reaction takes place through disproportionation of (bipyrimidine)Pd(OAc)2 to form a bipyrimidine-bridged dimer, which reacts with olefin to form a PdII-olefin adduct, followed by allylic C–H activation to produce (η3-allyl)PdII species. The (η3-allyl)PdII intermediate undergoes a reversible acetate attack to generate a Pd0-(allyl acetate) adduct, which subsequently reacts with p-benzoquinone to release allyl acetate and regenerate (bipyrimidine)Pd(OAc)2. No KIE is observed for the competition experiment between allylbenzene-d0 and allylbenzene-d5 (CD2=CDCD2C6H5), suggesting that allylic C–H activation is not rate-determining. Catalytic allylic acetoxylations of other terminal olefins as well as cyclohexene were also effected by (bipyrimidine)Pd(OAc)2.Key words: olefin, palladium catalysis, allylic C–H oxidation, p-benzoquinone, bipyrimidine.
A mechanistic study of the addition of alkynes to Brook silenes
Authors: Milnes Kaarina K , Baines Kim M
Published: December 2008

The addition of the alkyne-containing mechanistic probes (trans-2-phenylcyclopropyl)ethyne, (trans,trans-2-methoxy-3-phenylcyclopropyl)ethyne, and (trans,trans-2-methoxy-1-methyl-3-phenylcyclopropyl)ethyne (1a–1c) to a Brook silene 2-(1-adamantyl)-2-trimethylsiloxy-1,1-bis(trimethylsilyl)-1-silene (14) was examined. When alkyne 1a was added to the silene, an ene adduct was observed; however, addition of alkyne 1c to 14 gave a mixture of silacyclo butenes and silacycloheptenes. The regiochemistry of the phenyl and methoxy substituents on the seven-membered ring of the silacycloheptenes provides convincing evidence for the formation of a biradical intermediate along the reaction pathway.Key words: Brook silene, alkyne, cycloaddition, reaction mechanism, mechanistic probe.
Probing solid iminobis(diorganophosphine chalcogenide) systems with multinuclear magnetic resonance
Authors: Demko Bryan A , Wasylishen Roderick E
Published: December 2008

A 31P and 77Se solid-state NMR investigation of the iminobis(diorganophosphine chalcogenide) HN(R2PE)2 (R = Ph,iPr; E = O, S, Se) systems is presented. The NMR results are discussed in terms of the known HN(R2PE)2 structures available from X-ray crystallography. The phosphorus chemical shift tensors are found to be sensitive to the nature of the alkyl and chalcogen substituents. The nature of the R group also influences the selenium chemical shift tensors of HN(R2PSe)2 (R = Ph, iPr), which are shown to be sensitive to hydrogen bonding in the dimer structure of HN(Ph2PSe)2 and to the presence of disorder in the case of HN(iPr2PSe)2. Scalar relativistic ZORA DFT nuclear magnetic shielding tensor calculations were performed yielding the orientations of the corresponding chemical shift tensors. A theoretical investigation into the effect of the E-P···P-E “torsion” angle on the phosphorus and selenium chemical shift tensors of a truncated HN(Me2PSe)2 system indicates that the electronic effect of the alkyl group on the respective nuclear magnetic shielding tensors are more important than the steric effect of the E-P···P-E torsion angle.Key words: iminobis(diorganophosphine chalcogenide), solid-state NMR, 31P NMR, 77Se NMR, ZORA DFT.
Phenylene-1,4- and biphenylene-4,4′-diselenolate bridged complexes of gold(I)
Authors: Taher Deeb , Taylor Nicholas J , Corrigan John F
Published: December 2008

Homobimetallic gold-selenolate complexes of the type [(Ph2R)PAuSe(C6H4)nSeAuP(Ph2R)] (3a, R = Et, n = 1; 3b, R = Et, n = 2; 5a, R = Ph, n = 1; 5b, R = Ph, n = 2) are obtained by the reaction of [Ph2RPAuCl] (1, R = Et; 4, R = Ph) with 0.5 equiv. of Me3SiSe(C6H4)nSeSiMe3 (2a, n = 1; 2b, n = 2) in good yield. Complex [(Pr3P)AuSe(C6H4)2SeAu(PPr3)] 7b can be prepared in a two-step synthesis procedure: treatment of [AuCl(SMe2)] 6 with 0.5 equiv. of Me3SiSe(C6H4)2SeSiMe3 2b gives [(Me2S)AuSe(C6H4)2SeAu(SMe2)], which further reacts with PPr3 to afford 7b. The new gold-selenolate complexes have been characterized by multinuclear NMR (1H, 31P, 77Se) and elemental analysis. The solid state structures of 3b, 5a, and 7b were determined by single X-ray structure analysis.Key words: gold, dimer, selenolate, biphenylene, phenylene.
Tunable electrogenerated chemiluminescence from CdSe nanocrystals
Authors: Zhou Jigang , Zhu Jun , Brzezinski Jack , Ding Zhifeng
Published: December 2008

Electrochemical behavior and related optoelectronic properties of CdSe nanocrystals (NCs) in aprotic solutions have been investigated. NCs of 2.50 ± 0.50 nm diameter were synthesized using a modified procedure in which the temperatures at the time of Se precursor injection and NC growth were controlled. The electrochemical band gap was found to agree with those determined by UV–vis absorption spectroscopy and by the tunneling current-voltage spectrum in the literature. Electrogenerated chemiluminescence of the NCs with peak maxima at 1.90 eV (red, 653 nm) and 2.55 eV (blue, 486 nm) can be generated and altered by scanning the voltage between –1.60 and –1.80 V and between –2.00 and –2.20 V, respectively. The results demonstrate the potential capability of the NCs for light emission tuned by the applied potential.Key words: CdSe nanocrystals, electrochemistry, electrogenerated chemiluminescence, UV–vis spectroscopy, photoluminescence.
Prevalence of Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor and Soluble fms-Like Tyrosine Kinase 1 in a Gestational Age–Matched Case Study
Authors: Herse Florian , Verlohren Stefan , Wenzel Katrin , Pape Juliane , Muller Dominik N. , Modrow Susanne , Wallukat Gerd , Luft Friedrich C. , Redman Christopher W.G. , Dechend Ralf
Published: December 2008

We showed earlier that activating autoantibodies against the angiotensin II type 1 (AT
1
) receptor (AT1-AA) circulate in preeclamptic women. They may be involved in the pathogenesis of preeclampsia. Protein alignment suggests that the binding site for AT1-AAs is highly homologous to the capsid protein VP2 of parvovirus B19. We performed a prospective, nested, case-control study of 30 gestational age–matched women with preeclampsia and 30 normotensive pregnant women. We measured AT1-AA, soluble fms-like tyrosine kinase 1 (sFlt-1), and serum immunoglobulin G against parvovirus B19 proteins. AT1-AAs were present in 70% of preeclamptic patients and absent in 80% of controls. Prediction by AT1-AA was improved in late-onset preeclampsia. The discrimination for sFlt-1 was 96%. We did not find an interaction between sFlt-1 and AT1-AA. A human monoclonal immunoglobulin G antibody against parvovirus B19 VP2-protein showed a positive reaction in the AT1-AA bioassay, which could be blocked by an AT
1
receptor blocker, as well as by the epitope amino acid sequence. Immunoglobulin G against parvovirus B19 proteins was similarly distributed between preeclamptic patients and controls and had no significant importance. We detected significantly more AT1-AA in women with an immune response corresponding with parvovirus B19 infection corresponding with a distant viral infection associated with virus elimination. We concluded that AT1-AAs were common in patients with preeclampsia in a prospective case-control study, although sFlt-1 was a superior biomarker. AT1-AA may represent a better marker for late disease, whereas sFlt1 is a better marker for early onset disease.
Challenges of Designing Trials for the Primary Prevention of Stroke
Authors: Gorelick Philip B.
Published: December 2008

Background and Purpose—

Prevention of a first stroke is an important strategy to reduce morbidity and mortality associated with cerebrovascular disease. In this discussion, we review challenges to development of clinical trials for prevention of a first stroke.

Summary of Review—

We discuss prevention of first stroke in the context of clinical trial design in the ARRIVE trial and a primary prevention trial in development for the elderly.

Conclusions—

Stroke is an important outcome in cerebrovascular disease trials in the elderly, but it may be trumped by coronary heart disease as a more common end point.