A New Mechanism for β‐Lactamases: Class D Enzymes Degrade 1β‐Methyl Carbapenems through Lactone Formation

β‐Lactamases threaten the clinical use of carbapenems, which are considered antibiotics of last resort. The classical mechanism of serine carbapenemase catalysis proceeds through hydrolysis of an acyl‐enzyme intermediate. We show that class D β‐lactamases also degrade clinically used 1β‐methyl‐substituted carbapenems through the unprecedented formation of a carbapenem‐derived β‐lactone. β‐Lactone formation results from nucleophilic attack of the carbapenem hydroxyethyl side chain on the ester carbonyl of the acyl‐enzyme intermediate. The carbapenem‐derived lactone products inhibit both serine β‐lactamases (particularly class D) and metallo‐β‐lactamases. These results define a new mechanism for the class D carbapenemases, in which a hydrolytic water molecule is not required.     

Environmental analysis of organic compounds in water using solid phase micro extraction

Solid Phase Micro Extraction (SPME) involves exposing a fused silica fiber coated with stationary phase to a contaminated water sample. The organic analytes become partitioned between the stationary phase and the water and when equilibrium is reached the fiber is removed from the solution and the analytes are thermally desorbed in the injector of a gas chromatograph. The fiber is contained in a syringe to facilitate handling. Factors which affect linear range, limit of detection, and total analysis time are discussed with regard to the development of a method for analysis of volatile compounds in environmental water samples. The sensitivity of the method was determined by the thickness of the film of stationary phase; the equilibration time, however, increased with the film thickness, although it can be minimized by use of a cross-shaped stirrer bar. Increasing the thickness of stationary phase in the analytical column enables the cryofocusing temperature to be increased from ?40 to ?15°C. With an ion trap mass spectrometer, detection limits required by the US Environmental Protection Agency are met for all compounds except chloromethane and chloroethane. The method has been applied to environmental water samples.     

Insertion of acetylenes in the PdPd bond of Pd2 (Ph2 PCH2 PPh2)2 Cl2

Dimethylacetylene dicarboxylate and hexafluoro-2-butyne add to Pd₂(dpm)₂Cl₂ (dpm = Ph₂PCH₂PPh₂) to give crystalline adducts Pd₂(dp)₂(μ-acetylene)Cl₂. An X-ray crystal structure of Pd₂(dpm)₂(μ-C₄F₆)Cl₂ reveals that the acetylene has inserted into the metalmetal bond and has been transformed into a cis-dimetallated olefin. The central CC bond length of the bridging olefin is 1.338(16) Å. The coordination about each of the two similar palladium ions is planar and involves two trans-phosphines (one from each of the bridging dpm ligands), a terminal chloride, and one carbon of the bridging olefin. Both Pd₂(dpm)₂Cl₂ and Pd₂(dpm)₂(μ-C₂{CO₂H₃}₂)Cl₂ catalyze the cyclotrimerization of dimethyl-acetylene dicarboxylate.     

Magnetization depth profile of (Fe/Dy) multilayers

An experimental and numerical study of the magnetization in (Fe 3 nm/Dy 2 nm) multilayers is presented. The samples were thermally evaporated under ultra-high vacuum at two different substrate temperatures, 320 and 570 K. In order to get the magnetization depth profile of these transition metal/rare earth (TM/RE) multilayers, a fine investigation of the structural, chemical, and magnetic properties was carried out. The samples were studied by X-ray reflectivity (XRR), high resolution transmission electron microscopy (HRTEM), conversion electron Mössbauer spectrometry (CEMS), SQUID magnetometry and polarized neutron reflectivity (PNR). Magnetization profiles were obtained by Monte Carlo simulations to support the PNR fits. The key role of the crystalline structure is emphasized by magnetic depth profile measurements performed using polarized neutron reflectometry. The antiparallel configuration of Fe and Dy layers’ magnetizations was evidenced, as well as the perpendicular magnetic anisotropy (PMA), especially in the case of the sample prepared at 570 K.     

Reciprocal Response of Human Oral Epithelial Cells to Internalized Silica Nanoparticles

Silica nanoparticles (SiO₂ NPs) are one of the most widely used engineered nanoparticles and can been found in a wide range of consumer products. Despite their massive global production scale, little is known about their potential effects in the context of unintended exposure or ingestion. Using TR146 cells as an in vitro model of the human oral buccal mucosa, the uptake, spatial intracellular distribution, reactive oxygen species (ROS) production, inflammatory response, and cytotoxic effects of commercial SiO₂ NPs are examined. SiO₂ NPs are shown to dock and cross the cellular membrane barrier in a dose–time‐dependent manner. Confocal sectioning reveals translocation of SiO₂ NPs into the cell nucleus after 12 h of exposure. A concentration threshold of more than 500 × 10^?6 m is observed, above which SiO₂ NPs are shown to exert significant oxidative stress with concomitant upregulation of inflammatory genes IL6 and TNFA. Further analysis of the p53 pathway and a series of apoptotic and cell cycle biomarkers reveals intracellular accumulation of SiO₂ NPs exert marginal nanotoxicity. Collectively, this study provides important information regarding the uptake, intracellular distribution, and potential adverse cellular effects of SiO₂ NPs commonly found in consumer products in the human oral epithelium.     

Ultrafast electron pulses from a tungsten tip triggered by low-power femtosecond laser pulses

We present an experimental and numerical study of electron emission from a sharp tungsten tip triggered by sub-8-fs low-power laser pulses. This process is nonlinear in the laser electric field, and the nonlinearity can be tuned via the dc voltage applied to the tip. Numerical simulations of this system show that electron emission takes place within less than one optical period of the exciting laser pulse, so that an 8 fs 800 nm laser pulse is capable of producing a single electron pulse of less than 1 fs duration. Furthermore, we find that the carrier-envelope phase dependence of the emission process is smaller than 0.1% for an 8 fs pulse but is steeply increasing with decreasing laser pulse duration.     

Characterization of trabecular bone structure from high-resolution magnetic resonance images using fuzzy logic

The purpose of this work was to apply fuzzy logic image processing techniques to characterize the trabecular bone structure with high-resolution magnetic resonance images. Fifteen ex vivo high-resolution magnetic resonance images of specimens of human radii at 1.5 T and 12 in vivo high-resolution magnetic resonance images of the calcanei of peri- and postmenopausal women at 3 T were obtained. Soft segmentation using fuzzy clustering was applied to MR data to obtain fuzzy bone volume fraction maps, which were then analyzed with three-dimensional (3D) fuzzy geometrical parameters and measures of fuzziness. Geometrical parameters included fuzzy perimeter and fuzzy compactness, while measures of fuzziness included linear index of fuzziness, quadratic index of fuzziness, logarithmic fuzzy entropy, and exponential fuzzy entropy. Fuzzy parameters were validated at 1.5 T with 3D structural parameters computed from microcomputed tomography images, which allow the observation of true trabecular bone structure and with apparent MR structural indexes at 1.5 T and 3 T. The validation was statistically performed with the Pearson correlation coefficient as well as with the Bland-Altman method. Bone volume fraction correlation values (r) were up to .99 (P<.001) with good agreements based on Bland-Altman analysis showing that fuzzy clustering is a valid technique to quantify this parameter. Measures of fuzziness also showed consistent correlations to trabecular number parameters (r>.85; P<.001) and good agreements based on Bland-Altman analysis, suggesting that the level of fuzziness in high-resolution magnetic resonance images could be related to the trabecular bone structure.     

Experimental and computational analyses of the effects of slice distortion from a metallic sphere in an MRI phantom

Susceptibility artifacts due to metallic prostheses are a major problem in clinical magnetic resonance imaging. We theoretically and experimentally analyze slice distortion arising from susceptibility differences in a phantom consisting of a stainless steel ball bearing embedded in agarose gel. To relate the observed image artifacts to slice distortion, we simulate images produced by 2D and 3D spin-echo (SE) and a view angle tilting (VAT) sequence. Two-dimensional SE sequences suffer from extreme slice distortion when a metal prosthesis is present, unlike 3D SE sequences for which--since slices are phase-encoded--distortion of the slice profile is minimized, provided the selected slab is larger than the region of interest. In a VAT sequence, artifacts are reduced by the application of a gradient along the slice direction during readout. However, VAT does not correct for the excitation slice profile, which results in the excitation of spins outside the desired slice location and can lead to incorrect anatomical information in MR images. We propose that the best sequences for imaging in the presence of a metal prosthesis utilize 3D acquisition, with phase encoding replacing slice selection to minimize slice distortion, combined with excitation and readout gradient strengths at their maximum values.     

Volumetric imaging with an amplitude-steered array

Volumetric acoustic imaging is desirable for the visualization of underwater objects and structures; however, the implementation of a volumetric imaging system is difficult due to the high channel count of a fully populated two-dimensional array. Recently, a linear amplitude-steered array with a reduced electronics requirement was presented, which is capable of collecting a two-dimensional set of data with a single transmit pulse. In this study, we demonstrate the use of the linear amplitude-steered array and associated image formation algorithms for collecting and displaying volumetric data; that is, proof of principle of the amplitude-steering concept and the associated image formation algorithms is demonstrated. Range and vertical position are obtained by taking advantage of the frequency separation of a vertical linear amplitude-steered array. The third dimension of data is obtained by rotating the array such that the mainlobe is mechanically steered in azimuth. Data are collected in a water tank at the Pennsylvania State University Applied Research Laboratory for two targets: a ladder and three pipes. These data are the first experimental data collected with an amplitude-steered array for the purposes of imaging. The array is 10 cm in diameter and is operated in the frequency range of 80 to 304 kHz. Although the array is small for high-resolution imaging at these frequencies, the rungs of the ladder are recognizable in the images. The three pipes are difficult to discern in two of the projection images; however, the pipes separated in range are clear in the image showing vertical position versus range. The imaging concept is demonstrated on measured data, and the simulations agree well with the experimental results.