Sideband Cooling Micromechanical Motion to the Quantum Ground State

The advent of laser cooling techniques revolutionized the study of many atomic-scale systems. This has fueled progress towards quantum computers by preparing trapped ions in their motional ground state, and generating new states of matter by achieving Bose-Einstein condensation of atomic vapors. Analogous cooling techniques provide a general and flexible method for preparing macroscopic objects in their motional ground state, bringing the powerful technology of micromechanics into the quantum regime. Cavity opto- or electro-mechanical systems achieve sideband cooling through the strong interaction between light and motion. However, entering the quantum regime, less than a single quantum of motion, has been elusive because sideband cooling has not sufficiently overwhelmed the coupling of mechanical systems to their hot environments. Here, we demonstrate sideband cooling of the motion of a micromechanical oscillator to the quantum ground state. Entering the quantum regime requires a large electromechanical interaction, which is achieved by embedding a micromechanical membrane into a superconducting microwave resonant circuit. In order to verify the cooling of the membrane motion into the quantum regime, we perform a near quantum-limited measurement of the microwave field, resolving this motion a factor of 5.1 from the Heisenberg limit. Furthermore, our device exhibits strong-coupling allowing coherent exchange of microwave photons and mechanical phonons. Simultaneously achieving strong coupling, ground state preparation and efficient measurement sets the stage for rapid advances in the control and detection of non-classical states of motion, possibly even testing quantum theory itself in the unexplored region of larger size and mass.Comment: 13 pages, 7 figure

Complete Genome Sequence and Comparative Analysis of the Wild-type Commensal Escherichia coli Strain SE11 Isolated from a Healthy Adult

We sequenced and analyzed the genome of a commensal Escherichia coli (E. coli) strain SE11 (O152:H28) recently isolated from feces of a healthy adult and classified into E. coli phylogenetic group B1. SE11 harbored a 4.8 Mb chromosome encoding 4679 protein-coding genes and six plasmids encoding 323 protein-coding genes. None of the SE11 genes had sequence similarity to known genes encoding phage- and plasmid-borne virulence factors found in pathogenic E. coli strains. The comparative genome analysis with the laboratory strain K-12 MG1655 identified 62 poorly conserved genes between these two non-pathogenic strains and 1186 genes absent in MG1655. These genes in SE11 were mostly encoded in large insertion regions on the chromosome or in the plasmids, and were notably abundant in genes of fimbriae and autotransporters, which are cell surface appendages that largely contribute to the adherence ability of bacteria to host cells and bacterial conjugation. These data suggest that SE11 may have evolved to acquire and accumulate the functions advantageous for stable colonization of intestinal cells, and that the adhesion-associated functions are important for the commensality of E. coli in human gut habitat

Meningeal lymphatic endothelial cells fulfill scavenger endothelial cell function and cooperate with microglia in waste removal from the brain

Brain lymphatic endothelial cells (BLECs) constitute a group of loosely connected endothelial cells that reside within the meningeal layer of the zebrafish brain without forming a vascular tubular system. BLECs have been shown to readily endocytose extracellular cargo molecules from the brain parenchyma, however, their functional relevance in relation to microglia remains enigmatic. We here compare their functional uptake efficiency for several macromolecules and bacterial components with microglia in a qualitative and quantitative manner in 5-day-old zebrafish embryos. We find BLECs to be significantly more effective in the uptake of proteins, polysaccharides and virus particles as compared to microglia, while larger particles like bacteria are only ingested by microglia but not by BLECs, implying a clear distribution of tasks between the two cell types in the brain area. In addition, we compare BLECs to the recently discovered scavenger endothelial cells (SECs) of the cardinal vein and find them to accept an identical set of substrate molecules. Our data identifies BLECs as the first brain-associated SEC population in vertebrates, and demonstrates that BLECs cooperate with microglia to remove particle waste from the brain.Thrombosis and Hemostasi

Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate

Escherichia coli amine oxidase (ECAO), encoded by the tynA gene, catalyzes the oxidative deamination of aromatic amines into aldehydes through a well-established mechanism, but its exact biological role is unknown. We investigated the role of ECAO by screening environmental and human isolates for tynA and characterizing a tynA-deletion strain using microarray analysis and biochemical studies. The presence of tynA did not correlate with pathogenicity. In tynA+ Escherichia coli strains, ECAO enabled bacterial growth in phenylethylamine, and the resultant H2O2 was released into the growth medium. Some aminoglycoside antibiotics inhibited the enzymatic activity of ECAO, which could affect the growth of tynA+ bacteria. Our results suggest that tynA is a reserve gene used under stringent environmental conditions in which ECAO may, due to its production of H2O2, provide a growth advantage over other bacteria that are unable to manage high levels of this oxidant. In addition, ECAO, which resembles the human homolog hAOC3, is able to process an unknown substrate on human leukocytes

Primary Amine Oxidase of Escherichia coli Is a Metabolic Enzyme that Can Use a Human Leukocyte Molecule as a Substrate

Escherichia coli amine oxidase (ECAO), encoded by the tynA gene, catalyzes the oxidative deamination of aromatic amines into aldehydes through a well-established mechanism, but its exact biological role is unknown. We investigated the role of ECAO by screening environmental and human isolates for tynA and characterizing a tynA-deletion strain using microarray analysis and biochemical studies. The presence of tynA did not correlate with pathogenicity. In tynA+ Escherichia coli strains, ECAO enabled bacterial growth in phenylethylamine, and the resultant H2O2 was released into the growth medium. Some aminoglycoside antibiotics inhibited the enzymatic activity of ECAO, which could affect the growth of tynA+ bacteria. Our results suggest that tynA is a reserve gene used under stringent environmental conditions in which ECAO may, due to its production of H2O2, provide a growth advantage over other bacteria that are unable to manage high levels of this oxidant. In addition, ECAO, which resembles the human homolog hAOC3, is able to process an unknown substrate on human leukocytes.</p

The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

Quantum noise in a nano mechanical Duffing resonator

We determine the small signal gain and noise response of an amplifier based on the nonlinear response of a quantum nanomechanical resonator. The resonator is biased in the nonlinear regime by a strong harmonic bias force and we determine the response to a small additional driving signal detuned with respect to the bias force.Comment: submitted to the Focus Issue on 'Mechanical Systems at the Quantum Limit', edited by Markus Aspelmeyer and Keith Schwa

Hybrid SPECT/CT for the assessment of a painful hip after uncemented total hip arthroplasty

Background The diagnosis of hip pain after total hip replacement (THR) represents a highly challenging question that is of increasing concern to orthopedic surgeons. This retrospective study assesses bone scintigraphy with Hybrid SPECT/CT for the diagnosis of painful THR in a selected cohort of patients. Methods Bone SPECT/CT datasets of 23 patients (mean age 68.9 years) with a painful hip after THR were evaluated. Selection of the patients required an inconclusive radiograph, normal serum levels of inflammatory parameters (CRP and ESR) or a negative aspiration of the hip joint prior to the examination. The standard of reference was established by an interdisciplinary adjudication-panel using all imaging data and clinical follow-up data (>12 month). Pathological and physiological uptake patterns were defined and applied. Results The cause of pain in this study group could be determined in 18 out of 23 cases. Reasons were aseptic loosening (n = 5), spine-related (n = 5), heterotopic ossification (n = 5), neuronal (n = 1), septic loosening (n = 1) and periprosthetic stress fracture (n = 1). In (n = 5) cases the cause of hip pain could not be identified. SPECT/CT imaging correctly identified the cause of pain in (n = 13) cases, in which the integrated CT-information led to the correct diagnosis in (n = 4) cases, mainly through superior anatomic correlation. Loosening was correctly assessed in all cases with a definite diagnosis. Conclusions SPECT/CT of THA reliably detects or rules out loosening and provides valuable information about heterotopic ossifications. Furthermore differential diagnoses may be detected with a whole-body scan and mechanical or osseous failure is covered by CT- imaging. SPECT/CT holds great potential for imaging-based assessment of painful prostheses

The Complete Genome Sequence of Escherichia coli EC958: A High Quality Reference Sequence for the Globally Disseminated Multidrug Resistant E. coli O25b:H4-ST131 Clone

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage

High Prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae Detected in the Human Gut Using an Improved DNA Detection Protocol

Background: The low and variable prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae DNA in human stool contrasts with the paramount role of these methanogenic Archaea in digestion processes. We hypothesized that this contrast is a consequence of the inefficiencies of current protocols for archaeon DNA extraction. We developed a new protocol for the extraction and PCR-based detection of M. smithii and M. stadtmanae DNA in human stool. Methodology/Principal Findings: Stool specimens collected from 700 individuals were filtered, mechanically lysed twice, and incubated overnight with proteinase K prior to DNA extraction using a commercial DNA extraction kit. Total DNA was used as a template for quantitative real-time PCR targeting M. smithii and M. stadtmanae 16S rRNA and rpoB genes. Amplification of 16S rRNA and rpoB yielded positive detection of M. smithii in 95.7% and M. stadtmanae in 29.4% of specimens. Sequencing of 16S rRNA gene PCR products from 30 randomly selected specimens ( 15 for M. smithii and 15 for M. stadtmanae) yielded a sequence similarity of 99-100% using the reference M. smithii ATCC 35061 and M. stadtmanae DSM 3091 sequences. Conclusions/Significance: In contrast to previous reports, these data indicate a high prevalence of the methanogens M. smithii and M. stadtmanae in the human gut, with the former being an almost ubiquitous inhabitant of the intestinal microbiome