Tedizolid Activity Against Clinical Mycobacterium abscessus Complex Isolates—An in vitro Characterization Study

Mycobacterium abscessus complex consist of three rapidly growing subspecies: M. abscessus, M. massiliense, and M. bolletii. They are clinically important human pathogens responsible for opportunistic pulmonary and skin and soft tissue infections. Treatment of M. abscessus infections is difficult due to in vitro resistance to most antimicrobial agents. Tedizolid (TZD) is a next-generation oxazolidinone antimicrobial with a wide spectrum of activity even against multidrug resistant Gram-positive bacteria. In this study, the in vitro activity of TZD against the M. abscessus complex (n = 130) was investigated. Susceptibility testing by broth microdilution showed lower TZD minimum inhibitory concentrations (MICs) when compared to linezolid. The MIC50 and MIC90 was 1 mg/L and 4 mg/L, respectively across all M. abscessus complex members, reflecting no difference in subspecies response to TZD. Pre-exposure of M. abscessus complex to subinhibitory concentrations of TZD did not trigger any inducible drug resistance. Single-drug time kill assays and bactericidal activity assays demonstrated bacteriostatic activity of TZD in all three M. abscessus subspecies, even at high drug concentrations of 4 to 8x MIC. Combination testing of TZD with clarithromycin, doxycycline and amikacin using the checkerboard approach showed no antagonistic interactions. TZD may be an effective therapeutic antimicrobial agent for the treatment of M. abscessus infections

Influenza Excess Mortality from 1950–2000 in Tropical Singapore

10.1371/journal.pone.0008096PLoS ONE412

Tunable Emergent Heterostructures in a Prototypical Correlated Metal

At the interface between two distinct materials desirable properties, such as superconductivity, can be greatly enhanced, or entirely new functionalities may emerge. Similar to in artificially engineered heterostructures, clean functional interfaces alternatively exist in electronically textured bulk materials. Electronic textures emerge spontaneously due to competing atomic-scale interactions, the control of which, would enable a top-down approach for designing tunable intrinsic heterostructures. This is particularly attractive for correlated electron materials, where spontaneous heterostructures strongly affect the interplay between charge and spin degrees of freedom. Here we report high-resolution neutron spectroscopy on the prototypical strongly-correlated metal CeRhIn5, revealing competition between magnetic frustration and easy-axis anisotropy -- a well-established mechanism for generating spontaneous superstructures. Because the observed easy-axis anisotropy is field-induced and anomalously large, it can be controlled efficiently with small magnetic fields. The resulting field-controlled magnetic superstructure is closely tied to the formation of superconducting and electronic nematic textures in CeRhIn5, suggesting that in-situ tunable heterostructures can be realized in correlated electron materials

The spin-orbit angle of the transiting hot jupiter CoRoT-1b

We measure the angle between the planetary orbit and the stellar rotation axis in the transiting planetary system CoRoT-1, with new HIRES/Keck and FORS/VLT high-accuracy photometry. The data indicate a highly tilted system, with a projected spin-orbit angle lambda = 77 +- 11 degrees. Systematic uncertainties in the radial velocity data could cause the actual errors to be larger by an unknown amount, and this result needs to be confirmed with further high-accuracy spectroscopic transit measurements. Spin-orbit alignment has now been measured in a dozen extra-solar planetary systems, and several show strong misalignment. The first three misaligned planets were all much more massive than Jupiter and followed eccentric orbits. CoRoT-1, however, is a jovian-mass close-in planet on a circular orbit. If its strong misalignment is confirmed, it would break this pattern. The high occurence of misaligned systems for several types of planets and orbits favours planet-planet scattering as a mechanism to bring gas giants on very close orbits.Comment: to appear in in MNRAS letters [5 pages

Ultra-cold methods for polarized atomic hydrogen

Using the ultra-cold electron-spin-polarized atomic hydrogen technique, one can produce a slow monochromatic beam for use as a polarized jet target. We will first review the development of the ultra-cold technique and then discuss the recent progress on Michigan’s Mark-II ultra-cold proton-spin-polarized hydrogen jet target. © 1998 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87438/2/119_1.pd

Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4×10−6 (serial isolates) to 4.5×10−6 (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5–17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al

Analyzing power measurements in high‐P2∥ p‐p elastic scattering

The analyzing power in 28 GeV/c proton/proton elastic scattering was measured at P2∥=5.95 and 6.56 (GeV/c)2 using a polarized proton target and an unpolarized proton beam at the Brookhaven National Laboratory AGS. Results indicate that the analyzing power, A, is rising sharply with P2∥.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87401/2/1123_1.pd