Mild complexation protocol for chiral CpxRh and Ir complexes suitable for in situ catalysis.

A practical complexation method for chiral cyclopentadienyl (Cpx) iridium and rhodium complexes is described. The procedure uses the free CpxH with stable and commercially available rhodium(i) and iridium(i) salts without base or additive. The conditions are mild and do not require the exclusion of air and moisture. A salient feature is the suitability for in situ complexations enhancing the user-friendliness of Cpx ligands in asymmetric catalysis. DFT-calculations confirm an intramolecular proton abstraction pathway by either the bound acetate or methoxide. Furthermore, the superior facial selectivity of the proton abstraction step enabled the development of TMS-containing trisubstituted Cpx ligands which display improved enantioselectivities for the benchmarking dihydroisoquinolone synthesis.

Tailored trisubstituted chiral Cp x RhIII catalysts for kinetic resolutions of phosphinic amides.

A trisubstituted chiral Cp x ligand family is introduced. Based on the disubstituted atropchiral Cp x ligand scaffold, the introduction of a bulky third substituent at the central position of the Cp ring leads to substantially increased selectivities for rhodium(iii)-catalyzed kinetic resolutions and allowed for s-factors of up to 50. Their superiority is demonstrated by kinetic resolutions of phosphinic amides providing access to compounds with stereogenic phosphorus(v) atoms. The unreacted acyclic phosphinic amide and the cyclized product are both obtained in good yields and enantioselectivities. The ligand synthesis capitalizes on a late stage modification and expands the accessible ligand Cp x ligand portfolio.

A ß-Carbon elimination strategy for convenient in situ access to cyclopentadienyl metal complexes.

The electronic and steric properties of tailored cyclopentadienyl (Cp) ligands are powerful handles to modulate the catalytic properties of their metal complexes. This requires the individual preparation, purification and storage of each ligand/metal combination. Alternative, ideally in situ, complexation protocols would be of high utility. We disclose a new approach to access Cp metal complexes. Common metal precursors rapidly react with cyclopentadienyl carbinols via ß-carbon eliminations to directly give the Cp-metal complexes. An advantage of this is the direct and flexible use of storable pre-ligands. No auxiliary base is required and the Cp complexes can be prepared in situ in the reaction vessel for subsequent catalytic transformations.

Neutral chiral cyclopentadienyl Ru(ii)Cl catalysts enable enantioselective [2+2]-cycloadditions.

Cyclopentadienyl ruthenium(ii) complexes with a large number of available coordination sites are frequently used catalysts for a broad range of transformations. To be able to render these transformations enantioselective, we have designed a chiral neutral CpxRu(ii)Cl complex basing on an atropchiral cyclopentadienyl (Cpx) ligand which is accessed in a streamlined C-H functionalisation approach. The catalyst displays excellent levels of reactivity and enantioselectivity for enantioselective [2+2]-cycloadditions leading to strained chiral cyclobutenes, allowing for catalyst loadings as low as 1 mol%. A very strong counterion effect of a bound chloride anion transforms the corresponding unselective cationic complex into a highly enantioselective neutral version. Moreover, by adding norbornadiene at the end of the reaction the catalyst can be recovered and subsequently reused.

Neonatal listeriosis: Uncommon or misdiagnosed?

The incidence of perinatal and neonatal Listeriosis is underestimated due undiagnosed stillbirths, misdiagnosis of NL and underreporting of single case reports. Recent outbreaks reinforce the need for better surveillance and targeted health education in certain population groups especially during pregnancy.

Converting disulfide bridges in native peptides to stable methylene thioacetals.

Disulfide bridges play a crucial role in defining and rigidifying the three-dimensional structure of peptides. However, disulfides are inherently unstable in reducing environments. Consequently, the development of strategies aiming to circumvent these deficiencies - ideally with little structural disturbance - are highly sought after. Herein, we report a simple protocol converting the disulfide bond of peptides into highly stable methylene thioacetal. The transformation occurs under mild, biocompatible conditions, enabling the conversion of unprotected native peptides into analogues with enhanced stability. The developed protocol is applicable to a range of peptides and selective in the presence of a multitude of potentially reactive functional groups. The thioacetal modification annihilates the reductive lability and increases the serum, pH and temperature stability of the important peptide hormone oxytocin. Moreover, it is shown that the biological activities for oxytocin are retained.

Enantioselective palladium(0)-catalyzed intramolecular cyclopropane functionalization: access to dihydroquinolones, dihydroisoquinolones and the BMS-791325 ring system.

Taddol-based phosphoramidite ligands enable enantioselective palladium(0)-catalyzed C-H arylation of cyclopropanes. The cyclized products are obtained in high yields and enantioselectivities. The reported method provides efficient access to a broad range of synthetically attractive cyclopropyl containing dihydroquinolones and dihydroisoquinolones as well as allows for an efficient enantioselective construction of the 7-membered ring of the cyclopropyl indolobenzazepine core of BMS-791325.

Sinonasal persistence of Pseudomonas aeruginosa after lung transplantation.

UNLABELLED: We report on two CF patients who received double lung transplantation (LTX) due to Pseudomonas aeruginosa related pulmonary destruction. Prior to LTX we detected P. aeruginosa in nasal lavages (NL) and sputum cultures from both patients. Donor lungs of patient 1 became colonized within four weeks with P. aeruginosa identical in genotype with isolates from his pre-transplant sputum cultures and pre- and post-transplant NL. In contrast, patient 2 remained P. aeruginosa free in lower airway samples (bronchial lavage/sputum) for now up to 30 months, despite persistent detection of P. aeruginosa that was identical in genotype with pre-transplant NL and sputum isolates in NL and even in throat swabs. For prevention of pulmonary re-colonization patient 2 has continuously inhaled Colomycin 1 MIU once daily during the preceding more than 36 months with the novel Pari Sinus™ nebulizer, which in scintigraphic studies was shown to deliver vibrating aerosols into paranasal sinuses, additional to bronchial antibiotic inhalation. DISCUSSION: Pulmonary colonization of transplanted donor lungs with identical clones previously colonizing the explanted lungs has been described previously and the upper airways were postulated as reservoir for descending colonization. However, this remained speculative, as upper airway sampling which does not belong to current standards, was not performed in these studies. Our report demonstrates persistence of identical P. aeruginosa genotypes in CF upper airways prior to and after LTX underlining risks of descending colonization of transplanted lungs with P. aeruginosa, which increases risks of graft dysfunction. Therefore, we recommend regular assessment of sinonasal colonization prior to and after LTX. Sinonasal inhalation with antimicrobials should be investigated in prospective trials.

Recent advances and developments in composite dental restorative materials.

Composite dental restorations represent a unique class of biomaterials with severe restrictions on biocompatibility, curing behavior, esthetics, and ultimate material properties. These materials are presently limited by shrinkage and polymerization-induced shrinkage stress, limited toughness, the presence of unreacted monomer that remains following the polymerization, and several other factors. Fortunately, these materials have been the focus of a great deal of research in recent years with the goal of improving restoration performance by changing the initiation system, monomers, and fillers and their coupling agents, and by developing novel polymerization strategies. Here, we review the general characteristics of the polymerization reaction and recent approaches that have been taken to improve composite restorative performance.

Concordant genotype of upper and lower airways P aeruginosa and S aureus isolates in cystic fibrosis.

RATIONALE: Lower airway (LAW) infection with Pseudomonas aeruginosa and Staphylococcus aureus is the leading cause of morbidity in cystic fibrosis (CF). The upper airways (UAW) were shown to be a gateway for acquisition of opportunistic bacteria and to act as a reservoir for them. Therefore, tools for UAW assessment within CF routine care require evaluation. OBJECTIVES: The aims of the study were non-invasive assessment of UAW and LAW microbial colonisation, and genotyping of P aeruginosa and S aureus strains from both segments. METHODS: 182 patients with CF were evaluated (age 0.4-68 years, median 17 years). LAW specimens were preferably sampled as expectorated sputum and UAW specimens by nasal lavage. P aeruginosa and S aureus isolates were typed by informative single nucleotide polymorphisms (SNPs) or by spa typing, respectively. RESULTS: Of the typable S aureus and P aeruginosa isolates from concomitant UAW- and LAW-positive specimens, 31 of 36 patients were carrying identical S aureus spa types and 23 of 24 patients identical P aeruginosa SNP genotypes in both compartments. Detection of S aureus or P aeruginosa in LAW specimens was associated with a 15- or 88-fold higher likelihood also to identify S aureus or P aeruginosa in a UAW specimen from the same patient. CONCLUSIONS: The presence of identical genotypes in UAW and LAW suggests that the UAW play a role as a reservoir of S aureus and P aeruginosa in CF. Nasal lavage appears to be suitable for non-invasive UAW sampling, but further longitudinal analyses and comparison with invasive methods are required. While UAW bacterial colonisation is typically not assessed in regular CF care, the data challenge the need to discuss diagnostic and therapeutic standards for this airway compartment. TRIAL REGISTRATION NUMBER: NCT00266474.

Parametric instabilities in magnetized multicomponent plasmas.

This paper investigates the excitation of various natural modes in a magnetized bi-ion or dusty plasma. The excitation is provided by parametrically pumping the magnetic field. Here two ionlike species are allowed to be fully mobile. This generalizes our previous work where the second heavy species was taken to be stationary. Their collection of charge from the background neutral plasma modifies the dispersion properties of the pump and excited waves. The introduction of an extra mobile species adds extra modes to both these types of waves. We first investigate the pump wave in detail, in the case where the background magnetic field is perpendicular to the direction of propagation of the pump wave. Then we derive the dispersion equation relating the pump to the excited wave for modes propagating parallel to the background magnetic field. It is found that there are a total of twelve resonant interactions allowed, whose various growth rates are calculated and discussed.

Rotational modes of oscillation of rodlike dust grains in a plasma.

Three dimensional rotatory modes of oscillations in a one-dimensional chain of rodlike charged particles or dust grains in a plasma are investigated. The dispersion characteristics of the modes are analyzed. The stability of different equilibrium orientations of the rods, phase transitions between the different equilibria, and a critical dependence on the relative strength of the confining potential are analyzed. The relations of these processes with liquid crystals, nanotubing, and plasma coating are discussed.

Kinetics of plasma flowing around two stationary dust grains.

The characteristics of plasma particle kinetics in the presence of ions flowing around two stationary dust grains aligned in the direction of the flow are studied using a three-dimensional molecular dynamics simulation code. The dynamics of plasma electrons and ions as well as the charging process of the dust grain are simulated self-consistently. Distributions of electron and ion number densities, and the electrostatic plasma potential are obtained for various intergrain distances, including those much less, of the order of, and more than the plasma electron Debye length.

Self-excited vertical oscillations in an rf-discharge dusty plasma.

A self-excited vertical oscillation of dust grains in the sheath region of an rf-discharge plasma has been observed. The variation of amplitude with pressure and input power was measured. Dramatic increase of oscillation amplitude was found for pressures below 4.5 Pa. Possible excitation mechanisms are considered.

Dynamics of the charging and motion of a macroparticle in a plasma flow.

The dynamics of motion and charging of a macroscopic "dust" particle in a plasma with an ion flow is investigated by employing the particle-in-cell method. It is demonstrated that the charging and motion of the dust particle levitating in an external parabolic potential is related to the ion flow. This situation is relevant for the majority of experiments on the self-organization and crystallization of colloidal dust grains in a low-temperature plasma.

Plasma kinetics around a dust grain in an ion flow.

The kinetics of plasma particles around a stationary dust grain in the presence of an ion flow is studied using a three-dimensional molecular dynamics simulation method. The model is self-consistent, involving the dynamics of plasma electrons and ions as well as charging of the dust grain. The effect of ion focusing is investigated as a function of the ion flow velocity. Distributions of electron and ion number densities, and electrostatic plasma potential are obtained.

Effect of a dipole moment on the wake potential of a dust grain in a flowing plasma.

The effect of a dipole moment on the wake potential of a dust grain in a collisionless plasma with a supersonic ion flow is studied. It is found that both the point charge and the dipole moment can be responsible for the oscillatory potential behind the dust. The dipole moment is dominant in forming the wake potential when the dipole moment p becomes of the order of the absolute value (Q) lambda(D), where Q is the dust charge and lambda(D) is the Debye length.

Equilibrium and oscillations of grains in the dust-plasma crystal.

The dispersion characteristics of the low-frequency mode associated with vertical oscillations of dust grains in a quasi-two-dimensional dust-plasma crystal are calculated, taking into account the dependence of the dust charge on the local sheath potential. It is shown that the equilibrium of the dust grains close to the electrode may be disrupted by large amplitude vertical oscillations.

Five-year age-specific incidence rates. II: The accuracy of calculations of expected number of tumours.

Five-year age-specific incidence rates were shown to produce small but systematic errors in the calculation of the expected number of tumours in a hypothetical but realistic study population. Underestimates occurred at younger ages (under 55) and overestimates at older ages, with a small overestimate (0.22%) overall. Larger errors (up to 12%) were obtained when there was a rapid change in the single-year age structure of the study population. Interpolation between five-year rates will normally produce an inaccurate set of one-year rates. It is shown, with the example of a logarithmic interpolation, that these rates tend to produce errors of similar size to the five-year rates but with a small underestimate overall (0.37%). However, the interpolated rates produced the smaller errors (up to 1%) when the study population age structure undergoes rapid change. A method is suggested for partially correcting the error in the interpolated rates.