Prospective Multicenter Validation of the Stockholm3 Test in a Central European Cohort.

Background: It has been shown that the Stockholm3 test decreases overdetection of prostate cancer (PCa) while retaining the ability to detect clinically significant PCa (csPCa) in a Swedish population. However, the test includes potentially population-specific testing of single-nucleotide polymorphisms and has yet not been validated outside Scandinavia.

Objective: To assess the performance of the Stockholm3 test in discriminating csPCa in a Central European cohort undergoing prostate biopsy (PBx).

Levitated Optomechanics with Meta-Atoms.

We propose to introduce additional control in levitated optomechanics by trapping a meta-atom, i.e., a subwavelength and high-permittivity dielectric particle supporting Mie resonances.

Interaction between an Optically Levitated Nanoparticle and Its Thermal Image: Internal Thermometry via Displacement Sensing.

We propose and theoretically analyze an experiment where displacement sensing of an optically levitated nanoparticle in front of a surface can be used to measure the induced dipole-dipole interaction between the nanoparticle and its thermal image. This is achieved by using a surface that is transparent to the trapping light but reflective to infrared radiation, with a reflectivity that can be time modulated. This dipole-dipole interaction relies on the thermal radiation emitted by a silica nanoparticle having sufficient temporal coherence to correlate the reflected radiation with the thermal fluctuations of the dipole.

Cavity-Based 3D Cooling of a Levitated Nanoparticle via Coherent Scattering.

We experimentally realize cavity cooling of all three translational degrees of motion of a levitated nanoparticle in vacuum. The particle is trapped by a cavity-independent optical tweezer and coherently scatters tweezer light into the blue detuned cavity mode. For vacuum pressures around 10^{-5}  mbar, minimal temperatures along the cavity axis in the millikelvin regime are observed.

PBP2a in β-Lactam-Resistant Laboratory Mutants and Clinical Isolates: Disruption Versus Reduced Penicillin Affinity.

Alterations in PBP2a have been recognized in cefotaxime-resistant laboratory mutants and β-lactam-resistant clinical isolates of Streptococcus pneumoniae. DNA sequencing revealed fundamental differences between these two settings. Internal stop codons in pbp2a occurred in all three laboratory mutants analyzed, caused by a mutation in pbp2a of mutant C604, and tandem duplications within pbp2a resulting in premature stop codons in another two mutants C403 and C406.

Draft Genome Sequences of Two Serotype 19A Sequence Type 226 Clinical Isolates from Hungary, Hu17 with High-Level Beta-Lactam Resistance and Hu15 of a Penicillin-Sensitive Phenotype.

The draft genome sequences of two multiple-antibiotic-resistant isolates from Hungary, Hu15 and Hu17, are reported here. Strain Hu15 is penicillin susceptible, whereas Hu17 is a high-level-penicillin-resistant strain. Both isolates belong to the serotype 19A sequence type 226, a single-locus variant (in the locus) of the Hungary-6 clone.

New Aspects of the Interplay between Penicillin Binding Proteins, , and the Two-Component System CiaRH of Penicillin-Resistant Streptococcus pneumoniae Serotype 19A Isolates from Hungary.

The clone Hungary-6 expresses unusually high levels of β-lactam resistance, which is in part due to mutations in the MurM gene, encoding a transferase involved in the synthesis of branched peptidoglycan. Moreover, it contains the allele , encoding the histidine kinase CiaH (M. Müller, P.

Personalizing the Payment Process Builds Patient Satisfaction.

Messages specific to balance due amounts allow hospitals to tailor wording and payment options based on high or low balances.

Ultrashort Pulses for Far-Field Nanoscopy.

We show that ultrashort pulses can be focused, in a particular instant, to a spot size given by the wavelength associated with its spectral width. For attosecond pulses this spot size is within the nanometer scale. Then we show that a two-level system can be left excited after interacting with an ultrashort pulse whose spectral width is larger than the transition frequency, and that the excitation probability depends not on the field amplitude but on the field intensity.

Transfer of penicillin resistance from Streptococcus oralis to Streptococcus pneumoniae identifies murE as resistance determinant.

Beta-lactam resistant clinical isolates of Streptococcus pneumoniae contain altered penicillin-binding protein (PBP) genes and occasionally an altered murM, presumably products of interspecies gene transfer. MurM and MurN are responsible for the synthesis of branched lipid II, substrate for the PBP catalyzed transpeptidation reaction. Here we used the high-level beta-lactam resistant S.

Altered lipid composition in Streptococcus pneumoniae cpoA mutants.

Background: Penicillin-resistance in Streptococcus pneumoniae is mainly due to alterations in genes encoding the target enzymes for beta-lactams, the penicillin-binding proteins (PBPs). However, non-PBP genes are altered in beta-lactam-resistant laboratory mutants and confer decreased susceptibility to beta-lactam antibiotics. Two piperacillin resistant laboratory mutants of Streptococcus pneumoniae R6 contain mutations in the putative glycosyltransferase gene cpoA.

Generalized QM/MM Force Matching Approach Applied to the 11-cis Protonated Schiff Base Chromophore of Rhodopsin.

We extended a previously developed force matching approach to systems with covalent QM/MM boundaries and describe its user-friendly implementation in the publicly available software package CPMD. We applied this approach to the challenging case of the retinal protonated Schiff base in dark state bovine rhodopsin. We were able to develop a highly accurate force field that is able to capture subtle structural changes within the chromophore that have a pronounced influence on the optical properties.

Concerted and Sequential Proton Transfer Mechanisms in Water-Separated Acid-Base Encounter Pairs.

The proton transfer mechanisms involved inside aqueous, solvent-separated encounter complexes between phenol and carboxyl moieties are studied using ab initio molecular dynamics and computational time-resolved vibrational spectroscopy. This model framework can be viewed as a ground-state analog of the excited-state proton transfer reactions that have been actively investigated using ultrafast spectroscopy. Three qualitatively distinct proton transfer pathways are observed in the simulations.

Streptococcus pneumoniae R6 interspecies transformation: genetic analysis of penicillin resistance determinants and genome-wide recombination events.

Interspecies gene transfer has been implicated as the major driving force for the evolution of penicillin resistance in Streptococcus pneumoniae. Genomic alterations of S. pneumoniae R6 introduced during four successive transformations with DNA of the high-level penicillin-resistant Streptococcus mitis B6 with beta-lactam selection have now been determined and the contribution of genes to high resistance levels was analysed genetically.

Mutations in Streptococcus pneumoniae penicillin-binding protein 2x: importance of the C-terminal penicillin-binding protein and serine/threonine kinase-associated domains for beta-lactam binding.

Penicillin-binding protein 2x (PBP2x) mutations that occur during the selection with beta-lactams are located within the central penicillin-binding/transpeptidase (TP) domain, and are believed to mediate resistance by interfering with the formation of a covalent complex of the active site serine with the antibiotic. We now investigated the effect of two point mutations found in two independently obtained laboratory mutants that are located at the surface of the TP domain with their side chains facing outside (G422D respectively R426C). They have no significant effect on resistance to cefotaxime in vivo or on binding to Bocillin™FL to the active site in vitro using purified PBP2x derivatives, thus apparently do not affect the active site directly.

Molecular mechanisms of β-lactam resistance in Streptococcus pneumoniae.

Alterations in the target enzymes for β-lactam antibiotics, the penicillin-binding proteins (PBPs), have been recognized as a major resistance mechanism in Streptococcus pneumoniae. Mutations in PBPs that confer a reduced affinity to β-lactams have been identified in laboratory mutants and clinical isolates, and document an astounding variability of sites involved in this phenotype. Whereas point mutations are selected in the laboratory, clinical isolates display a mosaic structure of the affected PBP genes, the result of interspecies gene transfer and recombination events.

Genome of Streptococcus oralis strain Uo5.

Streptococcus oralis, a commensal species of the human oral cavity, belongs to the Mitis group of streptococci, which includes one of the major human pathogens as well, S. pneumoniae. We report here the first complete genome sequence of this species.

A computational study of ultrafast acid dissociation and acid-base neutralization reactions. II. The relationship between the coordination state of solvent molecules and concerted versus sequential acid dissociation.

We investigate the role played by the coordination state of pre-existing water wires during the dissociation of moderately strong acids by means of first-principles molecular dynamics calculations. By preparing 2,4,6-tricyanophenol (calc. pKa∼0.

A computational study of ultrafast acid dissociation and acid-base neutralization reactions. I. The model.

Ultrafast, time-resolved investigations of acid-base neutralization reactions have recently been performed using systems containing the photoacid 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and various Bronsted bases. Two conflicting neutralization mechanisms have been formulated by Mohammed et al. [Science 310, 83 (2005)] and Siwick et al.

On the formation of proton-shared and contact ion pair forms during the dissociation of moderately strong acids: an Ab initio molecular dynamics investigation.

Acid ionization and dissociation are phenomena that play a fundamental role in chemistry and biology, but their microscopic details are largely unknown. We use ab initio molecular dynamics to identify and characterize various structures that are formed along the pathway of dissociation of trifluoroacetic acid (pK(a) = 0.5).

The mammalian and yeast translocon complexes comprise a characteristic Sec61 channel.

In eukaryotes, protein translocation across and insertion into the membrane of the endoplasmic reticulum (ER) is facilitated by a protein-conducting channel, the Sec61 complex or translocon. In our previous electrophysiological studies, we characterized the mammalian Sec61 channel from Canis familiaris. Here we extended these initial results to the Sec61 channel from the yeast Saccharomyces cerevisiae and compared the basic electrophysiological properties of both channel preparations with respect to the gating behaviour, distribution of channel open states, ionic conductance, approximated pore dimensions, reversal potential and selectivity as well as voltage-dependent open probability.

The genome of Streptococcus mitis B6--what is a commensal?

Streptococcus mitis is the closest relative of the major human pathogen S. pneumoniae. The 2,15 Mb sequence of the Streptococcus mitis B6 chromosome, an unusually high-level beta-lactam resistant and multiple antibiotic resistant strain, has now been determined to encode 2100 genes.

Combining ab initio quantum mechanics with a dipole-field model to describe acid dissociation reactions in water: first-principles free energy and entropy calculations.

We introduce a novel approach to compute dissociation free energy and entropy values in simulations that employ a density functional theory description of the acidic moiety and of the solvent. The approach consists of utilizing an alchemical transformation of a weak acid A-COOH into the strong acid B-COOH, which makes it practical to employ alchemical free energy perturbation methods in the context of ab initio molecular dynamics simulations. The present alchemical transformation circumvents the need to tackle changes in the total number of electrons and atoms by replacing the chemical residue responsible for the change in acidity with an easily tunable external effective potential.