bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3receptor activation in thioglycollate-induced peritonitis
Authors: Montesinos M Carmen , Desai Avani , Cronstein Bruce N
Published: March 2006

Prior studies demonstrate that adenosine, acting at one or more of its receptors, mediates the anti-inflammatory effects of methotrexate in animal models of both acute and chronic inflammation. Both adenosine A2A and A3 receptors contribute to the anti-inflammatory effects of methotrexate treatment in the air pouch model of inflammation, and the regulation of inflammation by these two receptors differs at the cellular level. Because different factors may regulate inflammation at different sites we examined the effect of low-dose weekly methotrexate treatment (0.75 mg/kg/week) in a model of acute peritoneal inflammation in adenosine A2A receptor knockout mice and A3 receptor knockout mice and their wild-type littermates. Following intraperitoneal injection of thioglycollate there was no significant difference in the number or type of leukocytes, tumor necrosis factor alpha (TNF-α) and IL-10 levels that accumulated in the thioglycollate-induced peritoneal exudates in adenosine A2A knockout mice or wild-type control mice. In contrast, there were more leukocytes, TNF-α and IL-10 in the exudates of the adenosine A3 receptor-deficient mice. Low-dose, weekly methotrexate treatment increased the adenosine concentration in the peritoneal exudates of all mice studied, and reduced the leukocyte accumulation in the wild-type mice and A3 receptor knockout mice but not in the A2A receptor knockout mice. Methotrexate reduced exudate levels of TNF-α in the wild-type mice and A3 receptor knockout mice but not the A2A receptor knockout mice. More strikingly, IL-10, a critical regulator of peritoneal inflammation, was increased in the methotrexate-treated wild-type mice and A3 knockout mice but decreased in the A2A knockout mice. Dexamethasone, an agent that suppresses inflammation by a different mechanism, was similarly effective in wild-type mice, A2A mice and A3 knockout mice. These findings provide further evidence that adenosine is a potent regulator of inflammation that mediates the anti-inflammatory effects of methotrexate. Moreover, these data provide strong evidence that the anti-inflammatory effects of methotrexate and adenosine are mediated by different receptors in different inflammatory loci, an observation that may explain why inflammatory diseases of some organs but not of other organs respond to methotrexate therapy.
Enhanced expression of mRNA for nuclear factor κB1 (p50) in CD34+ cells of the bone marrow in rheumatoid arthritis
Authors: Hirohata Shunsei , Miura Yasushi , Tomita Tetsuya , Yoshikawa Hideki , Ochi Takahiro , Chiorazzi Nicholas
Published: March 2006

Bone marrow CD34+ cells from rheumatoid arthritis (RA) patients have abnormal capacities to respond to tumor necrosis factor (TNF)-α and to differentiate into fibroblast-like cells producing matrix metalloproteinase (MMP)-1. We explored the expression of mRNA for nuclear factor (NF)κB in RA bone marrow CD34+ cells to delineate the mechanism for their abnormal responses to TNF-α. CD34+ cells were purified from bone marrow samples obtained from 49 RA patients and 31 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The mRNAs for NFκB1 (p50), NFκB2 (p52) and RelA (p65) were examined by quantitative RT-PCR. The expression of NFκB1 mRNA in bone marrow CD34+ cells was significantly higher in RA than in OA, whereas there was no significant difference in the expression of mRNA for NFκB2 and RelA. The expression of NFκB1 mRNA was not correlated with serum C-reactive protein or with the treatment with methotrexate or oral steroid. Silencing of NFκB1 by small interfering RNA abrogated the capacity of RA bone marrow CD34+ cells to differentiate into fibroblast-like cells and to produce MMP-1 and vascular endothelial growth factor upon stimulation with stem cell factor, granulocyte-macrophage colony stimulating factor and TNF-α without influencing their viability and capacity to produce β2-microglobulin. These results indicate that the enhanced expression of NFκB1 mRNA in bone marrow CD34+ cells plays a pivotal role in their abnormal responses to TNF-α and, thus, in the pathogenesis of RA.
Lung and 'end organ' injury due to mechanical ventilation in animals: comparison between the prone and supine positions
Authors: Nakos George , Batistatou Anna , Galiatsou Eftychia , Konstanti Eleonora , Koulouras Vassilios , Kanavaros Panayotis , Doulis Apostolos , Kitsakos Athanassios , Karachaliou Angeliki , Lekka Marilena E , Bai Maria
Published: March 2006

Introduction

Use of the prone position in patients with acute lung injury improves their oxygenation. Most of these patients die from multisystem organ failure and not from hypoxia, however. Moreover, there is some evidence that the organ failure is caused by increased cell apoptosis. In the present study we therefore examined whether the position of the patients affects histological changes and apoptosis in the lung and 'end organs', including the brain, heart, diaphragm, liver, kidneys and small intestine.

Methods

Ten mechanically ventilated sheep with a tidal volume of 15 ml/kg body weight were studied for 90 minutes. Five sheep were placed in the supine position and five sheep were placed in the prone position during the experiment. Lung changes were analyzed histologically using a semiquantitative scoring system and the extent of apoptosis was investigated with the TUNEL method.

Results

In the supine position intra-alaveolar hemorrhage appeared predominantly in the dorsal areas, while the other histopathologic lesions were homogeneously distributed throughout the lungs. In the prone position, all histological changes were homogeneously distributed. A significantly higher score of lung injury was found in the supine position than in the prone position (4.63 ± 0.58 and 2.17 ± 0.19, respectively) (P < 0.0001). The histopathologic changes were accompanied by increased apoptosis (TUNEL method). In the supine position, the apoptotic index in the lung and in most of the 'end organs' was significantly higher compared with the prone position (all P < 0.005). Interestingly, the apoptotic index was higher in dorsal areas compared with ventral areas in both the prone and supine positions (P < 0.003 and P < 0.02, respectively).

Conclusion

Our results suggest that the prone position appears to reduce the severity and the extent of lung injury, and is associated with decreased apoptosis in the lung and 'end organs'.
Predicting late anemia in critical illness
Authors: Milbrandt Eric B , Clermont Gilles , Martinez Javier , Kersten Alex , Rahim Malik T , Angus Derek C
Published: March 2006

Introduction

Identifying critically ill patients most likely to benefit from pre-emptive therapies will become increasingly important if therapies are to be used safely and cost-effectively. We sought to determine whether a predictive model could be constructed that would serve as a useful decision support tool for the pre-emptive management of intensive care unit (ICU)-related anemia.

Methods

Our cohort consisted of all ICU patients (n = 5,170) admitted to a large tertiary-care academic medical center during the period from 1 July 2000 to 30 June 2001. We divided the cohort into development (n = 3,619) and validation (n = 1,551) sets. Using a set of demographic and physiologic variables available within six hours of ICU admission, we developed models to predict patients who either received late transfusion or developed late anemia. We then constructed a point system to quantify, within six hours of ICU admission, the likelihood of developing late anemia.

Results

Models showed good discrimination with receiver operating characteristic curve areas ranging from 0.72 to 0.77, although predicting late transfusion was consistently less accurate than predicting late anemia. A five-item point system predicted likelihood of late anemia as well as existing clinical trial inclusion criteria but resulted in pre-emptive intervention more than two days earlier.

Conclusion

A rule-based decision support tool using information available within six hours of ICU admission may lead to earlier and more appropriate use of blood-sparing strategies.
Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis
Authors: Davidson Warren J , Dorscheid Del , Spragg Roger , Schulzer Michael , Mak Edwin , Ayas Najib T
Published: March 2006

Introduction

The purpose of this study was to perform a systematic review and meta-analysis of exogenous surfactant administration to assess whether this therapy may be useful in adult patients with acute respiratory distress syndrome.

Methods

We performed a computerized literature search from 1966 to December 2005 to identify randomized clinical trials. The primary outcome measure was mortality 28–30 days after randomization. Secondary outcome measures included a change in oxygenation (PaO2:FiO2 ratio), the number of ventilation-free days, and the mean duration of ventilation. Meta-analysis was performed using the inverse variance method.

Results

Two hundred and fifty-one articles were identified. Five studies met our inclusion criteria. Treatment with pulmonary surfactant was not associated with reduced mortality compared with the control group (odds ratio 0.97; 95% confidence interval (CI) 0.73, 1.30). Subgroup analysis revealed no difference between surfactant containing surface protein or not – the pooled odds ratio for mortality was 0.87 (95% CI 0.48, 1.58) for trials using surface protein and the odds ratio was 1.08 (95% CI 0.72, 1.64) for trials without surface protein. The mean difference in change in the PaO2:FiO2 ratio was not significant (P = 0.11). There was a trend for improved oxygenation in the surfactant group (pooled mean change 13.18 mmHg, standard error 8.23 mmHg; 95% CI -2.95, 29.32). The number of ventilation-free days and the mean duration of ventilation could not undergo pooled analysis due to a lack of sufficient data.

Conclusion

Exogenous surfactant may improve oxygenation but has not been shown to improve mortality. Currently, exogenous surfactant cannot be considered an effective adjunctive therapy in acute respiratory distress syndrome.
The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database
Authors: Harrison David A , Welch Catherine A , Eddleston Jane M
Published: March 2006

Introduction

To evaluate the impact of recent evidence-based treatments for severe sepsis in routine clinical care requires an understanding of the underlying epidemiology, particularly with regard to trends over time. We interrogated a high quality clinical database to examine trends in the incidence and mortality of severe sepsis over a nine-year period.

Methods

Admissions with severe sepsis occurring at any time within 24 hours of admission to critical care were identified to an established methodology using raw physiological data from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, containing data from 343,860 admissions to 172 adult, general critical care units in England, Wales and Northern Ireland between December 1995 and January 2005. Generalised linear models were used to assess changes in the incidence, case mix, outcomes and activity of these admissions.

Results

In total, 92,672 admissions (27.0%) were identified as having severe sepsis in the first 24 hours following admission. The percentage of admissions with severe sepsis during the first 24 hours rose from 23.5% in 1996 to 28.7% in 2004. This represents an increase from an estimated 18,500 to 31,000 admissions to all 240 adult, general critical care units in England, Wales and Northern Ireland. Hospital mortality for admissions with severe sepsis decreased from 48.3% in 1996 to 44.7% in 2004, but the total number of deaths increased from an estimated 9,000 to 14,000. The treated incidence of severe sepsis per 100,000 population rose from 46 in 1996 to 66 in 2003, with the associated number of hospital deaths per 100,000 population rising from 23 to 30.

Conclusion

The population incidence of critical care admission with severe sepsis during the first 24 hours and associated hospital deaths are increasing. These baseline data provide essential information to those wishing to evaluate the introduction of the Surviving Sepsis Campaign care bundles in UK hospitals.
Comparative evaluation of linear and exponential amplification techniques for expression profiling at the single-cell level
Authors: Subkhankulova Tatiana , Livesey Frederick J
Published: March 2006

Background

Single-cell microarray expression profiling requires 108-109-fold amplification of the picogram amounts of total RNA typically found in eukaryotic cells. Several methods for RNA amplification are in general use, but little consideration has been given to the comparative analysis of those methods in terms of the overall validity of the data generated when amplifying from single-cell amounts of RNA, rather than their empirical performance in single studies.

Results

We tested the performance of three methods for amplifying single-cell amounts of RNA under ideal conditions: T7-based in vitro transcription; switching mechanism at 5' end of RNA template (SMART) PCR amplification; and global PCR amplification. All methods introduced amplification-dependent noise when mRNA was amplified 108-fold, compared with data from unamplified cDNA. PCR-amplified cDNA demonstrated the smallest number of differences between two parallel replicate samples and the best correlation between independent amplifications from the same cell type, with SMART outperforming global PCR amplification. SMART had the highest true-positive rate and the lowest false-positive rate when comparing expression between two different cell types, but had the lowest absolute discovery rate of all three methods. Direct comparison of the performance of SMART and global PCR amplification on single-cell amounts of total RNA and on single neural stem cells confirmed these findings.

Conclusion

Under the conditions tested, PCR amplification was more reliable than linear amplification for detecting true expression differences between samples. SMART amplification had a higher true-positive rate than global amplification, but at the expense of a considerably lower absolute discovery rate and a systematic compression of observed expression ratios.
Large-scale gene discovery in the pea aphid Acyrthosiphon pisum(Hemiptera)
Authors: Sabater-Muñoz Beatriz , Legeai Fabrice , Rispe Claude , Bonhomme Joël , Dearden Peter , Dossat Carole , Duclert Aymeric , Gauthier Jean-Pierre , Ducray Danièle Giblot , Hunter Wayne , Dang Phat , Kambhampati Srini , Martinez-Torres David , Cortes Teresa , Moya Andrès , Nakabachi Atsushi , Philippe Cathy , Prunier-Leterme Nathalie , Rahbé Yvan , Simon Jean-Christophe , Stern David L , Wincker Patrick , Tagu Denis
Published: March 2006

Aphids are the leading pests in agricultural crops. A large-scale sequencing of 40,904 ESTs from the pea aphid Acyrthosiphon pisum was carried out to define a catalog of 12,082 unique transcripts. A strong AT bias was found, indicating a compositional shift between Drosophila melanogaster and A. pisum. An in silico profiling analysis characterized 135 transcripts specific to pea-aphid tissues (relating to bacteriocytes and parthenogenetic embryos). This project is the first to address the genetics of the Hemiptera and of a hemimetabolous insect.
Receptor-Interacting Protein 140 Is a Repressor of the Androgen Receptor Activity
Authors: Carascossa Sophie , Gobinet Jérôme , Georget Virginie , Lucas Annick , Badia Eric , Castet Audrey , White Roger , Nicolas Jean-Claude , Cavaillès Vincent , Jalaguier Stéphan
Published: March 2006

The androgen receptor (AR) is a ligand-activated transcription factor that controls growth and survival of prostate cancer cells. In the present study, we investigated the regulation of AR activity by the receptor-interacting protein 140 (RIP140). We first showed that RIP140 could be coimmunoprecipitated with the receptor when coexpressed in 293T cells. This interaction appeared physiologically relevant because chromatin immunoprecipitation assays revealed that, under R1881 treatment, RIP140 could be recruited to the prostate-specific antigen encoding gene in LNCaP cells. In vitro glutathione S-transferase pull-down assays provided evidence that the carboxy-terminal domain of AR could interact with different regions of RIP140. By means of fluorescent proteins, we demonstrated that ligand-activated AR was not only able to translocate to the nucleus but also to relocate RIP140 from very structured nuclear foci to a diffuse pattern. Overexpression of RIP140 strongly repressed AR-dependent transactivation by preferentially targeting the ligand binding domain-dependent activity. Moreover, disruption of RIP140 expression induced AR overactivation, thus revealing RIP140 as a strong AR repressor. We analyzed its mechanism of transrepression and first demonstrated that different regions of RIP140 could mediate AR-dependent repression. We then showed that the carboxy-terminal end of RIP140 could reverse transcriptional intermediary factor 2-dependent overactivation of AR. The use of mutants of RIP140 allowed us to suggest that C-terminal binding protein played no role in RIP140-dependent inhibition of AR activity, whereas histone deacetylases partly regulated that transrepression. Finally, we provided evidence for a stimulation of RIP140 mRNA expression in LNCaP cells under androgen treatment, further emphasizing the role of RIP140 in androgen signaling.
Surgical Management of Acute Epidural Hematomas
Authors: Bullock M Ross , Chesnut Randall , Ghajar Jamshid , Gordon David , Hartl Roger , Newell David W. , Servadei Franco , Walters Beverly C. , Wilberger Jack E.
Published: March 2006

RECOMMENDATIONS (see Methodology)

Indications for Surgery

Timing

Methods
Surgical Management of Posterior Fossa Mass Lesions
Authors: Bullock M Ross , Chesnut Randall , Ghajar Jamshid , Gordon David , Hartl Roger , Newell David W. , Servadei Franco , Walters Beverly C. , Wilberger Jack
Published: March 2006

RECOMMENDATIONS (see Methodology)

Indications

Timing

Methods
Derivatization in Mass Spectrometry—7. On-Line Derivatization/Degradation
Authors: Halket John M. , Zaikin Vladimir G.
Published: March 2006

The review describes on-line derivatization/degradation methods employed in mass spectrometry to solve some structural and analytical problems. Advantages and applications of various positions of reaction systems connected mainly to a mass spectrometer or a gas chromatograph/mass spectrometer are considered. Among these are reaction systems connected directly to the mass spectrometer (reaction mass spectrometry, pyrolysis-mass spectrometry or direct pyrolysis-mass spectrometry); flash-heaters as reactors in gas chromatography/mass spectrometry (GC/MS); in-line chemical reactors located before the chromatographic column [pre-column derivatization/degradation with the use of catalytic reactions, pyrolysis (pyrolysis-GC/MS), degradation in elemental analyzers-isotope ratio mass pectrometry (EA-IRMS)]; on-column derivatization and deuteration; reactor located between the chromatographic column and a mass spectrometer [post-column catalytic derivatization, gas chromatograph-combustion-isotope ratio mass spectrometer (GC-c-IRMS)]. Post-column derivatization in high performance liquid chromatography/mass spectrometry is briefly mentioned. Application of such on-line methodology to structure elucidation of low molecular mass compounds and polymers, to the determination of isotope ratios of the most common elements, to the investigation of catalytic reactions is discussed.
Electron Ionization Mass Spectra and Tautomerism of 2-Phenacylpyridines
Authors: Martiskainen Olli , Gawinecki Ryszard , Ośmiałowski Borys , Pihlaja Kalevi
Published: March 2006

The electron ionization mass spectra of 2-phenacylpyridine (ketimine form) and its 13 derivatives substituted in the benzene ring (1a–n: a R = H, b 3-Me, c 4-Me, d 4-NH2, e 3-F, f 4-F, g 4-OMe, h 4-Cl, i 4-N(CH3)2, j 4-NO2, k 4-CF3, l 4-N(CH2)4, m 4-Br, n 3-Br) were recorded at 70 eV to determine the fragmentation routes and to screen the presence of their enolimine tautomers, ( Z-)-2-(2-hydroxy-2-phenylvinyl)pyridines in the gas phase. The total ion currents (TIC) of the ions [M – H]+, [M – HCO]+, 2-PyCH2O+, and RC6H4CO+ (= ArCO+) showed a fair or good correlation with the Hammett σ constants ( R = 0.859, 0.876, 0.912, and −0.926, respectively). The relative abundances ( RA) of both the [M – CO]+• and the [M – HCO]+ ion increased with the decreasing electron donating ability of the substituents and also correlated relatively well with the Hammett constants ( R = 0.834 and 0.907, respectively). These observations, in comparison to the NMR results, show that the relative contribution of the ketimine tautomer also increases in the gas phase with the increasing electron donating ability of the phenyl substituent, i.e. the TIC of the ArCO+ ion decreases whereas that of [M – H]+ ion increases.
Letter: Steric Effects in Electrospray-Tandem Mass Spectrometry of 11β-Nitrates of Estrane Series
Authors: Kadentsev V.I. , Chizhov A.O. , Chizhov O.S. , Krupinova O.N. , Rzheznikov V.M. , Golubovskaya L.E.
Published: March 2006

The fragmentation of [M + Na]+ ions produced from steroid 11β-nitrates during electrospray ionization (ESI) was studied by using the ion trap MS/MS technique. The [M + Na]+ ions eliminate NO2 and HNO3 for epimers bearing 9β and 9α substituents, respectively. As the main fragmentation pathways are determined mainly by the configuration at C-9 and alternative fragmentation hardly occur, this offers the possibility for deteermining the configurationof the estrane 11β nitrate series at the chiral C-9 center using ESI mass spectrometry.
Efficient Clustering of Cyclic Sulphonium Salts Applying Liquid Secondary Ion Mass Spectrometry
Authors: Cozzolino Rosaria , Gallagher Richard T. , Drewello Thomas
Published: March 2006

Salt-like cluster ions of the ([cation] n[anion] n–1)+ type are commonly composed of mono-atomic, inorganic components. Clusters containing organic ions are also known, with nitrogen-centred cations being particularly prominent. However, sulphur-centred analogues, such as organic sulphonium salts, represent a notable exception. Fast atom bombardment and liquid secondary ion mass spectrometry of such compounds show, in general, a low tendency towards the formation of clusters. The present study reveals that sputtering of cyclic sulphonium salts leads to the efficient formation of cluster ions beyond previous observations. Cluster ions are characterised by isotopic pattern analysis and collision-induced dissociation.
Mass Spectrometric Sequencing and Acylation Character Analysis of the C-Terminal Anchoring Segment from Influenza A Hemagglutinin
Authors: Serebryakova Marina V. , Kordyukova Larisa V. , Baratova Ludmila A. , Markushin Stanislav G.
Published: March 2006

Influenza A virus hemagglutinin (HA) is a major envelope glycoprotein mediating viral and cell membrane fusion. HA is anchored in the viral envelope by a light HA2 chain containing one transmembrane domain and a cytoplasmic tail. Three cysteine residues in the C-terminal region, one in the transmembrane domain and two in the cytoplasmic tail, are highly conserved and potentially palmitoylated in all HA subtypes. The HA2 C-terminal anchoring segments were extracted to organic phase from the bromelain-digested viruses (subviral particles) of three strains: A/X-31 (H3 subtype), A/Puerto Rico/8/34 (H1 subtype) and A/FPV/Weybridge/34 (H7 subtype). Their primary structures were assessed by matrix-assisted laser desorption/ionization time-of-flight time-of-flight mass spectrometry (MALDI-ToF-ToF MS). Trypsin-type protease-cleaved peptides prevailed over bromelain-cleaved ones in the peptide mixtures. All of them included transmembrane domains. Several distinctive features of the C-terminal HA2 peptides acylation character were discovered by MALDI-ToF MS: 1) the peptides isolated from the viruses, which were digested by bromelain in the absence of β-mercaptoethanol, were predominantly triply acylated; 2) the peptides were acylated not only by palmitic, but also by stearic acid residues; 3) the palmitate/stearate ratio was different for the three strains studied; 4) the A/FPV/Weybridge/34 strain has a priority to stearate binding. This fatty acid residue was discovered at the first of three conservative cysteine residues located in the transmembrane domain. It was found that presence of thiol reagent during preparation of subviral particles led to the appearence of the C-terminal HA2 peptides acylated to different degrees. Triply, doubly, mono-and even unacylated peptides were detected. It was demonstrated that the thioester bond in the isolated acylpeptides was extremely sensitive to thiol reagents.
Electrospray Ionization Tandem Mass Spectrometry Determined Regioisomeric Structures of Disubstituted β-Cyclodextrin Derivatives
Authors: Yamamura Hatsuo , Iwata Toshifumi , Kawai Masao , Sato Akihiro
Published: March 2006

Electrospray ionization tandem mass spectrometry was applied to the analysis of regiospecifically disubstituted β-cyclodextrins. Each disubstituted regioisomer showed unique fragmentation, distinguishing each of them unambiguously. These results demonstrate that mass spectrometry is the most straightforward method among those reported in the assignment of regioisomeric structures of these oligosaccharides.
Transition-metal-catalyzed reactions of allenes
Authors: Ma Shengming
Published: March 2006

Pathways for carbometallation of simple allenes and allenes bearing a nucleophilic functionality with RMX have been discussed. The bisallene approaches for the efficient synthesis of carbocycles and heterocycles have been developed.
Toward an understanding of the factors responsible for the 1,2-migration of alkyl groups in borate complexes
Authors: Aggarwal Varinder K. , Fang Guang Yu , Ginesta Xavier , Howells Dean M. , Zaja Mirko
Published: March 2006

The anionotropic 1,2-migration of an organic substituent from a tetrasubstituted borate ion, often referred to as an "ate" complex, to an acceptor atom is at the basis of the most useful application of organoboranes in organic synthesis. We recently showed that chiral sulfur ylides react with boranes to give homologated products with high enantiomeric excess. In considering reactions with mixed boranes, the issue of which group would migrate arises. Although we are primarily interested in sulfur ylide reactions with boranes, in this review we have summarized the most important factors that are responsible for which group migrates from a broad spectrum of reactions involving borate complexes. We also discuss the use of blocking/nonmigrating groups and highlight when they are effective and not effective. Consideration of the most important factors that affect the outcome of which group migrates and understanding how and why blocking groups work, provides a strategy for designing boranes with nonmigrating groups for use in new reactions of these useful synthetic intermediates.
Photochemical release of various functional groups
Authors: Bochet Christian G.
Published: March 2006

The photochemical liberation of functional groups is an attractive alternative to the traditional chemical approach. Several photolabile protecting groups have been developed in the past decades, but they were mainly designed to protect amines and carboxylic acids. In this account, we present some of our recent work on the photochemical release of other functions, such as silanols, aldehydes, and ketones. We also describe a new form of differentiation among several photolabile groups by the use of monochromatic light tuned to each of them: the chromatic orthogonality.
GaCl3-catalyzed reactions utilizing isocyanides as a C1 source
Authors: Tobisu Mamoru , Oshita Masayuki , Yoshioka Sachiko , Kitajima Aki , Chatani Naoto
Published: March 2006

Two GaCl3-catalyzed reactions, which utilize isocyanides as a one-carbon unit, are described: a [4+1] cycloaddition of α,β-unsaturated carbonyl compounds with isocyanides, and an insertion reaction of isocyanides into a C-O bond of ketals and acetals. The relatively low affinity of GaCl3 toward heteroatoms enables the successful catalysis.
Catalytic activation of nitrogen derivatives with transition-metal complexes
Authors: Lebel Hélène , Leogane Olivier , Huard Kim , Lectard Sylvain
Published: March 2006

Studies regarding the transition-metal-catalyzed decomposition of nitrogen derivatives toward Curtius rearrangement and the formation of nitrenes which undergo C-H insertion and aziridination reactions are presented. These processes lead to the formation of C-N bond with a high level of selectivity and efficiency.
New technologies in catalysis using base metals
Authors: Lipshutz Bruce H. , Butler Tom , Frieman Bryan A. , Kogan Vladimir , Lee Ching-Tien , Lower Asher , Nihan Danielle M. , Taft Benjamin R. , Tomaso Anthony E.
Published: March 2006

Formation of C-C, C-N, and C-H bonds using three heterogeneous catalysts in the form of nickel-in-charcoal (Ni/C), nickel-on-graphite (Ni/Cg), and copper-in-charcoal (Cu/C) are described.
Synthesis of spiroketals by iridium-catalyzed double hydroalkoxylation
Authors: Messerle Barbara A. , Vuong Khuong Q.
Published: March 2006

A highly efficient approach to the synthesis of spiroketals involves the double cyclization of alkynyl diols using transition-metal catalysts. The iridium complex [Ir(PyP)(CO)2]BPh4 where PyP = 1-[(2-diphenylphosphino)ethyl]pyrazole is an effective catalyst for promoting the formation of spiroketals via this double hydroalkoxylation reaction. The complex promotes the formation of a series of spiroketal products from alkynyl diol starting materials such as 3-ethynylpentane-1,5-diol and 2-(4-hydroxybut-1-ynyl)benzyl alcohol. Stereoselective cyclization occurs for 3-ethynylpentane-1,5-diol, 3-ethynylhexane-1,6-diol. The cycloadditions occur in all but one case with quantitative conversion in under 24 h at 120 °C.
Chiral Ru/PNNP complexes in catalytic and stoichiometric electrophilic O- and F-atom transfer to 1,3-dicarbonyl compounds
Authors: Bonaccorsi Cristina , Althaus Martin , Becker Claus , Togni Antonio , Mezzetti Antonio
Published: March 2006

The asymmetric hydroxylation and fluorination catalyst [Ru(OEt2)2(PNNP)]2+ (PNNP = chiral tetradentate ligand with a P2N2 donor set) reacts with 1,3-dicarbonyl compounds to give dicationic adducts and, upon deprotonation, the corresponding enolato complexes. The relevance of these species to catalytic O- and F-transfer is investigated.
Alkoxy- and hydroxycyclization of enynes catalyzed by Pd(II) and Pt(II) catalysts
Authors: Michelet Véronique , Charruault Lise , Gladiali Serafino , Genêt Jean-Pierre
Published: March 2006

The development of a novel reaction ideal in terms of atom economy was achieved. The scope of the reaction was evaluated in the presence of Pd and Pt catalysts. The first enantioselective Pt-promoted enyne carboalkoxycyclization was developed in up to 85 % stereoselectivity. This ideal atom-economical reaction afforded the corresponding functionalized five-membered carbo- and heterocycles in good to excellent yields. The use of silver salts combined with (R)-Ph-BINEPINE, a monophosphane atropisomeric ligand, was found to be the best-suited combination for moderate to high enantioselectivities on carbonated and nitrogenated substrates.
Dual Lewis acid - Lewis base activation in enantioselective additions to aldehydes
Authors: Wingstrand Erica , Lundgren Stina , Penhoat Maël , Moberg Christina
Published: March 2006

Reaction of benzaldehyde with ethyl cyanoformate in the presence of Lewis acidic Ti(IV) complexes of bispyridylamide or salen ligands and Lewis basic amines affords the O-alkoxycarbonylated cyanohydrin. In the presence of the salen-based catalytic system, acetyl cyanide can also be added to benzaldehyde, providing a highly enantioselective direct route to the O-acetylated cyanohydrin.
Indium-catalyzed addition of carbon units to acetylenes: Development of a new C-C bond formation toward exploitation of chemical resources
Authors: Nakamura Masaharu
Published: March 2006

This account deals with an overview of the development of catalytic addition reactions of carbonyl compounds to alkynes catalyzed by a variety of indium salts. The new C-C bond formation reactions provide a powerful tool for α-functionalization of carbonyl compounds, including direct α-vinylation with acetylene, regioselective α-alkenylation, and α-ynenylation that can be applied to a modular synthesis of α-arylated β-keto esters.
New synthetic reactions catalyzed by cobalt complexes
Authors: Yorimitsu Hideki , Oshima Koichiro
Published: March 2006

Without suffering from β-elimination, cobalt complexes allow cross-coupling reactions of alkyl halides with Grignard reagents. A combination of a cobalt complex and trimethylsilylmethyl Grignard reagent effects Mizoroki-Heck-type reaction of alkyl halide with styrene, which conventional palladium catalysts have never made possible. Cobalt exhibits intriguing catalytic activities on hydrophosphination and allylzincation of alkynes. Silylmethylcobalt reagent is a powerful tool for the synthesis of highly silylated ethenes.
Catalytic asymmetric ring-opening of cyclopentadiene - heterodienophile cycloadducts with organometallic reagents
Authors: Pineschi Mauro , Del Moro Federica , Crotti Paolo , Macchia Franco
Published: March 2006

An unprecedented catalytic asymmetric ring-opening of easily accessible 2,3-heterosubstituted norbornenes with hard alkyl metals (R-M), is able to give a practical regio- and stereoselective access to hetero-functionalized alkyl cyclopentenes in an enantioenriched form. The copper-catalyzed desymmetrization reaction with trialkylaluminums of sterically hindered and rigid, tri- or tetracyclic Diels-Alder adducts, easily available by cycloaddition reaction of cyclopentadiene with 4-phenyl-urazole and 2,3-phthalazine-1,4-dione, proved to be particularly efficient. Interestingly, the chirality of the amine part of the BINOL-based phosphoramidite is able to impose the absolute stereochemistry of the corresponding adducts.
Helicity control in the synthesis of helicenes and related compounds
Authors: Starý Ivo , Stará Irena G. , Alexandrová Zuzana , Sehnal Petr , Teplý Filip , Šaman David , Rulíšek Lubomír
Published: March 2006

Asymmetric synthesis of helicenes and their congeners has been demonstrated to rely either on enantioselective Ni0/PR3
*-catalyzed [2+2+2] cycloisomerization of triynes or on diastereoselective CoI-catalyzed [2+2+2] cycloisomerization of chiral triynes. The former approach providing tetrahydrohelicenes in a nonracemic form requires further development as moderate enantioselectivities (up to 54 % ee) have so far been achieved under kinetic control. The latter approach affording helicene-like structures in a diastereomerically enriched form allows for reaching good to excellent diastereoselectivities (up to 100:0) under thermodynamic control.
Rhodium-catalyzed asymmetric hydrogenation using self-assembled chiral bidentate ligands
Authors: Takacs James M. , Chaiseeda Kittichai , Moteki Shin A. , Reddy D. Sahadeva , Wu Di , Chandra Kusumlata
Published: March 2006

The chirality-directed self-assembly of bifunctional subunits around a structural metal - typically, zinc(II) - is used to form a heteroleptic complex in which a second set of ligating groups are suitably disposed to bind a second metal, forming a heterobimetallic catalyst system. We find that subtle changes in the structural backbone (i.e., ligand scaffold) of such chiral bidentate self-assembled ligands (SALs) can be used to manipulate the ligand topography and chiral environment around catalytic metal; thus, the scaffold can be optimized to maximize asymmetric induction. Using this combinatorial strategy for ligand synthesis, a preliminary study was carried out in which a library of 110 SALs was evaluated in the rhodium-catalyzed asymmetric hydrogenation of a simple N-acyl enamide. The level of enantioselectivity obtained varies from near racemic to greater than 80 % ee as a function of the ligand scaffold, with the possibility of further improvement yet to be explored.
Dabbling with air-stable organoaluminum species
Authors: Biswas Kallolmay , Chapron Alex , Cooper Thea , Fraser Paul K. , Novak Andrew , Prieto Oscar , Woodward Simon
Published: March 2006

Highly stereoselective 1,2-additions of AlMe3 or its air-stable analog DABCO(AlMe3)2 to aldehydes are realized in the presence of a Ni(acac)2-derived catalyst using phosphoramidite ligands giving sec-alcohols in up to 95 % ee. Very high turnover number (TON) (>1500) and turnover frequency (TOF) (>350 h-1) values can be realized in these reactions. The substrate range, trials of various (DABCO)
a
(AlR3)
b
reagents (a = 0.1; b = 1.2; R = Me, Et, Bu
i
), ligands, and molecular modeling studies are used to propose a working model for the catalytic cycle and the origin of the stereoselectivity. The phosphoramidite ligand is proposed to bind the nickel in an η2 manner via the P-donor and one of the C=C aryl bonds of the CHAr amine group. Preliminary studies indicate that DABCO(AlMe3)2 can also be used as a methyl source in Pd-catalyzed cross-coupling reactions of ArX (X = Br, I) species.
Asymmetric protonation of silyl enolates catalyzed by chiral phosphine-silver(I) complexes
Authors: Yanagisawa Akira , Touge Taichiro , Arai Takayoshi
Published: March 2006

A catalytic asymmetric protonation of trimethylsilyl enolates was achieved using a 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP)-silver(I) fluoride complex as a chiral catalyst in a mixed solvent consisting of dichloromethane and methanol. Various nonracemic ketones possessing a tertiary asymmetric carbon at the α-position were prepared with high enantioselectivity up to 99 % ee.
In Vitro Formation of Enteric Neural Network Structure in a Gut-Like Organ Differentiated from Mouse Embryonic Stem Cells
Authors: Takaki Miyako , Nakayama Shinsuke , Misawa Hiromi , Nakagawa Tadashi , Kuniyasu Hiroki
Published: March 2006

Using an embryoid body (EB) culture system, we developed a functional organ-like cluster—a “gut”—from mouse embryonic stem (ES) cells (ES gut). Each ES gut exhibited spontaneous contractions but did not exhibit distinct peristalsis-like movements. In these spontaneously contracting ES guts, dense distributions of interstitial cells of Cajal (c-kit [a transmembrane receptor that has tyrosine kinase activity]-positive cells; gut pacemaker cells) and smooth muscle cells were discernibly identified; however, enteric neural ganglia were absent in the spontaneously differentiated ES gut. By adding brain-derived neurotrophic factor (BDNF) only during EB formation, we for the first time succeeded in in vitro formation of enteric neural ganglia with connecting nerve fiber tracts (enteric nervous system [ENS]) in the ES gut. The ES gut with ENS exhibited strong peristalsis-like movements. During EB culture in BDNF+ medium, we detected each immunoreactivity associated with the trk proto-oncogenes (trkB; BDNF receptors) and neural crest marker, proto-oncogene tyrosine-protein kinase receptor ret precursor (c-ret), p75, or sox9. These results indicated that the present ENS is differentiated from enteric neural crest-derived cells. Moreover, focal stimulation of ES guts with ENS elicited propagated increases in intracellular Ca2+ concentration ([Ca2+]i) at single or multiple sites that were attenuated by atropine or abolished by tetrodotoxin. These results suggest in vitro formation of physiologically functioning enteric cholinergic excitatory neurons. We for the first time succeeded in the differentiation of functional neurons in ENS by exogenously adding BDNF in the ES gut, resulting in generation of distinct peristalsis-like movements.
Passive and active earth pressures in the presence of groundwater flow
Authors: Benmebarek N. , Benmebarek S. , Kastner R. , Soubra A.-H.
Published: March 2006

This paper deals with the effect of seepage flow on the lateral earth pressures acting on deep sheeted excavations in cohesionless soil. The computation of the passive and active earth pressures in the presence of hydraulic gradients is performed using the explicit finite difference method implemented in Fast Lagrangian Analysis of Continua (FLAC) code. The available effective passive earth pressure coefficients in the presence of upward seepage forces are given for both associative and non-associative material. The present solutions show that the soil dilation angle influences the effective passive earth pressures for large internal friction angle values of the soil. They also show that the effective passive pressures diminish with the hydraulic head loss. Good agreement is observed between the present results and those using an upper-bound approach in limit analysis for an associative material. For the active case, the effect of downward seepage forces on the active earth pressures is investigated. The numerical results show a significant increase in the effective active earth pressures due to a hydraulic head loss. It is also shown that the dilation angle influences the effective active earth pressures for large internal friction angle values.
A Coulomb-type solution for active earth thrust with seepage
Authors: Barros P. L. A.
Published: March 2006

A Coulomb-type general solution for active earth pressure on the vertical face of a retaining wall with a drainage system along the soil–structure interface is presented. The soil is cohesionless and fully saturated to the ground horizontal surface. This condition may happen during heavy rainfall and is the most critical, when the active pressure reaches its peak value. In order to solve the problem, a theoretical, closed-form solution for the water seepage through the soil is first developed. This is used in a Coulomb-type formulation, which supposes a plane failure surface inside the backfill when the wall movement is enough to put the soil mass in the active state. The formulation provides Coulomb-like coefficients of active pressure, which solve the problem in a generic way. Comparison with published results obtained by hand calculation shows very good agreement. A table with values of the coefficients of active earth pressure with seepage calculated for selected values of the soil internal friction angle and of the wall–soil friction angle is presented.
Pressuremeter tests in municipal solid waste: measurement of shear stiffness
Authors: Dixon N. , Whittle R. W. , Jones D. R. V. , Ng'ambi S.
Published: March 2006

To assess the long-term integrity, and hence adequate performance, of landfill lining systems the designer must consider interaction between lining components and the waste body. Information on typical ranges of waste mechanical properties is required for use in numerical modelling of this interaction. This paper presents results from a programme of pressuremeter testing in municipal solid waste (MSW) carried out to measure shear stiffness properties. An optimum procedure has been developed using a high-pressure dilatometer in a preformed test pocket. Tests have been conducted in fresh and partially degraded MSW deposits. Values of shear moduli for small to intermediate strains have been obtained from series of unload–reload loops, and these show a strong relationship between shear modulus and depth. Stiffness increases with cavity strain owing to drained cavity expansion. A clear linear relationship has been found between shear stiffness and stress level. Results for fresh MSW from two landfill sites show close agreement. Good agreement has been found between shear stiffness values calculated for small strain in pressuremeter tests and shear stiffness values measured using the continuous surface wave method. They also compare well with the limited amount of information in the literature.
Modelling of bond between three-wire strands and concrete
Authors: Bolmsvik R. , Lundgren K.
Published: March 2006

The bond between strands and concrete is of importance for prestressed concrete. The research presented in the current paper aims at a better understanding of the bond mechanism, and of how different detailings of the strand interface affect the behaviour. A bond model for three-wire strands was established and calibrated by use of pull-through tests. The results from finite element (FE) analyses with the bond model and the tests were used in parallel. It was found that adhesion, friction and the ability to develop normal stresses determine the bond response of the strand; consequently, they were used as input parameters in the bond model. How different detailing of the strand surface affects these parameters, and the influence on the bond mechanism, are shown. For example, adhesion has the strongest influence on the initial bond response in the cases of smooth and indented strands. Regarding indented strands, the maximum bond capacity is determined by the strand indentation. The knowledge gained can be used to design the strands for a certain bond behaviour.
Autogenous deformations and viscoelasticity of UHPFRC in structures. Part I: experimental results
Authors: Habel K. , Charron J.-P. , Denarié E. , Brühwiler E.
Published: March 2006

Autogenous shrinkage is the main driving force for internal deformations in ultra-high performance fibre-reinforced concretes (UHPFRC). Autogenous deformations and viscoelasticity are determined with free and restrained shrinkage tests for one kind of UHPFRC at an early age. The magnitude of free autogenous shrinkage is very strong during the first hours after hardening with 150 μm/m at 48 h and 325 μm/m at seven days. Long-term tests show that autogenous shrinkage becomes virtually constant at 90 days. The creep deformations of the fully restrained test amount to 60% of the free shrinkage deformations. Another experimental programme conducted on composite ‘UHPFRC–concrete’ beams shows that their time-dependent deformations are strongly influenced by the autogenous shrinkage of UHPFRC; however no visible cracking is induced in the structural elements.
Recent site and laboratory studies of surface densification in high-alumina cement concrete
Authors: Dunster A. M. , Holton I. R. , Crammond N. J.
Published: March 2006

The occurrence of a surface densification layer in both site and laboratory-cast high-alumina cement (HAC) concretes has been studied using a combination of permeability determinations and mineralogical analyses. Such a protective ‘skin’ occurred in many of the site concretes that were examined and this has been reproduced in the laboratory in cases where a sufficiently high-temperature gradient was achieved between the concrete surface and its interior.