Low-Noise Amplification of a Continuous Variable Quantum State

We present an experimental realization of a low-noise, phase-insensitive optical amplifier using a four-wave mixing interaction in hot Rb vapor. Performance near the quantum limit for a range of amplifier gains, including near unity, can be achieved. Such low-noise amplifiers are essential for so-called quantum cloning machines and are useful in quantum information protocols. We demonstrate that amplification and ``cloning'' of one half of a two-mode squeezed state is possible while preserving entanglement.Comment: To appear in Physical Review Letters July 3rd. 4 pages, 4 figure

Optical detection of single non-absorbing molecules using the surface plasmon of a gold nanorod

Current optical detection schemes for single molecules require light absorption, either to produce fluorescence or direct absorption signals. This severely limits the range of molecules that can be detected, because most molecules are purely refractive. Metal nanoparticles or dielectric resonators detect non-absorbing molecules by a resonance shift in response to a local perturbation of the refractive index, but neither has reached single-protein sensitivity. The most sensitive plasmon sensors to date detect single molecules only when the plasmon shift is amplified by a highly polarizable label or by a localized precipitation reaction on the particle's surface. Without amplification, the sensitivity only allows for the statistical detection of single molecules. Here we demonstrate plasmonic detection of single molecules in realtime, without the need for labeling or amplification. We monitor the plasmon resonance of a single gold nanorod with a sensitive photothermal assay and achieve a ~ 700-fold increase in sensitivity compared to state-of-the-art plasmon sensors. We find that the sensitivity of the sensor is intrinsically limited due to spectral diffusion of the SPR. We believe this is the first optical technique that detects single molecules purely by their refractive index, without any need for photon absorption by the molecule. The small size, bio-compatibility and straightforward surface chemistry of gold nanorods may open the way to the selective and local detection of purely refractive proteins in live cells

Joint synthesis of conditionally related multiple outcomes makes better use of data than separate meta-analyses

Background: When there are structural relationships between outcomes reported in different trials, separate analyses of each outcome do not provide a single coherent analysis, which is required for decision-making. For example, trials of intrapartum anti-bacterial prophylaxis (IAP) to prevent early onset group B streptococcal (EOGBS) disease can report three treatment effects: the effect on bacterial colonisation of the newborn, the effect on EOGBS, and the effect on EOGBS conditional on newborn colonisation. These outcomes are conditionally related, or nested, in a multi-state model. This paper shows how to exploit these structural relationships, providing a single coherent synthesis of all the available data, while checking to ensure that different sources of evidence are consistent. Results: Overall, the use of IAP reduces the risk of EOGBS (RR: 0.03; 95% Credible Interval (CrI): 0.002-0.13). Most of the treatment effect is due to the prevention of colonisation in newborns of colonised mothers (RR: 0.08, 95% CrI: 0.04-0.14). Node-splitting demonstrated that the treatment effect calculated using only direct evidence was consistent with that predicted from the remaining evidence (p=0.15). The findings accorded with previously published separate meta-analyses of the different outcomes, once these are re-analysed correctly accounting for zero cells. Conclusion: Multiple outcomes should be synthesised together where possible, taking account of their structural relationships. This generates an internally coherent analysis, suitable for decision making, in which estimates of each of the treatment effects are based on all available evidence (direct and indirect). Separate meta-analyses of each outcome have none of these properties

Imaging the Two Gaps of the High-TC Superconductor Pb-Bi2Sr2CuO6+x

The nature of the pseudogap state, observed above the superconducting transition temperature TC in many high temperature superconductors, is the center of much debate. Recently, this discussion has focused on the number of energy gaps in these materials. Some experiments indicate a single energy gap, implying that the pseudogap is a precursor state. Others indicate two, suggesting that it is a competing or coexisting phase. Here we report on temperature dependent scanning tunneling spectroscopy of Pb-Bi2Sr2CuO6+x. We have found a new, narrow, homogeneous gap that vanishes near TC, superimposed on the typically observed, inhomogeneous, broad gap, which is only weakly temperature dependent. These results not only support the two gap picture, but also explain previously troubling differences between scanning tunneling microscopy and other experimental measurements.Comment: 6 page

Transport of Explosive Residue Surrogates in Saturated Porous Media

Department of Defense operational ranges may become contaminated by particles of explosives residues (ER) as a result of low-order detonations of munitions. The goal of this study was to determine the extent to which particles of ER could migrate through columns of sandy sediment, representing model aquifer materials. Transport experiments were conducted in saturated columns (2 × 20 cm) packed with different grain sizes of clean sand or glass beads. Fine particles (approximately 2 to 50 μm) of 2,6-dinitrotoluene (DNT) were used as a surrogate for ER. DNT particles were applied to the top 1 cm of sand or beads in the columns, and the columns were subsequently leached with artificial groundwater solutions. DNT migration occurred as both dissolved and particulate phases. Concentration differences between unfiltered and filtered samples indicate that particulate DNT accounted for up to 41% of the mass recovered in effluent samples. Proportionally, more particulate than dissolved DNT was recovered in effluent solutions from columns with larger grain sizes, while total concentrations of DNT in effluent were inversely related to grain size. Of the total DNT mass applied to the uppermost layer of the column, <3% was recovered in the effluent with the bulk remaining in the top 2 cm of the column. Our results suggest there is some potential for subsurface migration of ER particles and that most of the particles will be retained over relatively short transport distances

Antenatal screening for Group B Streptococcus: A diagnostic cohort study

BACKGROUND: A range of strategies have been adopted to prevent early onset Group B Streptococcal (EOGBS) sepsis, as a consequence of Group B Streptococcal (GBS) vertically acquired infection. This study was designed to provide a scientific basis for optimum timing and method of GBS screening in an Australian setting, to determine whether screening for GBS infection at 35–37 weeks gestation has better predictive values for colonisation at birth than screening at 31–33 weeks, to examine the test characteristics of a risk factor strategy and to determine the test characteristics of low vaginal swabs alone compared with a combination of perianal plus low vaginal swabs per colonisation during labour. METHODS: Consented women received vaginal and perianal swabs at 31–33 weeks gestation, 35–38 weeks gestation and during labour. Swabs were cultured on layered horse blood agar and inoculated into selective broth prior to analysis. Test characteristics were calculated with exact confidence intervals for a high risk strategy and for antenatal screening at 31–33 and 35–37 weeks gestation for vaginal cultures alone, perianal cultures alone and combined low vaginal and perianal cultures. RESULTS: The high risk strategy was not informative in predicting GBS status during labour. There is an unequivocal benefit for the identification of women colonised with GBS during labour associated with delaying screening until 36 weeks however the results for method of screening were less definitive with no clear advantage in using a combined low vaginal and perianal swabbing regimen over the use of a low vaginal swab alone. CONCLUSION: This study can contribute to the development of prevention strategies in that it provides clear evidence for optimal timing of swabs. The addition of a perianal swab does not confer clear benefit. The quantification of advantages and disadvantages provided in this study will facilitate communication with clinicians and pregnant women alike

An investigation of horizontal transfer of feed introduced DNA to the aerobic microbiota of the gastrointestinal tract of rats

Background: Horizontal gene transfer through natural transformation of members of the microbiota of the lower gastrointestinal tract (GIT) of mammals has not yet been described. Insufficient DNA sequence similarity for homologous recombination to occur has been identified as the major barrier to interspecies transfer of chromosomal DNA in bacteria. In this study we determined if regions of high DNA similarity between the genomes of the indigenous bacteria in the GIT of rats and feed introduced DNA could lead to homologous recombination and acquisition of antibiotic resistance genes. Results: Plasmid DNA with two resistance genes (nptII and aadA) and regions of high DNA similarity to 16S rRNA and 23S rRNA genes present in a broad range of bacterial species present in the GIT, where constructed and added to standard rat feed. Six rats, with a normal microbiota, were fed DNA containing pellets daily over four days before sampling of the microbiota from the different GI compartments (stomach, small intestine, cecum and colon). In addition, two rats were included as negative controls. Antibiotic resistant colonies growing on selective media were screened for recombination with feed introduced DNA by PCR targeting unique sites in the putatively recombined regions. Conclusions: The analyses showed that extensive ingestion of DNA (100 \ub5g plasmid) per day did not lead to increased proportions of kanamycin resistant bacteria, nor did it produce detectable transformants among the aerobic microbiota examined for 6 rats (detection limit <1 transformant per 1.1 x 108 cultured bacteria). The key methodological challenges to HGT detection in animal feedings trials are identified and discussed

Evolutionary Emergence of microRNAs in Human Embryonic Stem Cells

Human embryonic stem (hES) cells have unique abilities to divide indefinitely without differentiating and potential to differentiate into more than 200 cell types. These properties make hES cells an ideal model system for understanding early human development and for regenerative medicine. Molecular mechanisms including cellular signaling and transcriptional regulation play important roles in hES cell differentiation. However, very little information is available on posttranscriptional regulation of hES cell pluripotency, self-renewal, and early decisions about cell fate. microRNAs (miRNAs), 22-nt long non-coding small RNAs found in plants and animals, regulate gene expression by targeting mRNAs for cleavage or translation repression. In hES cells we found that 276 miRNAs were expressed; of these, a set of 30 miRNAs had significantly changed expression during differentiation. Using a representative example, miR-302b, we show that miRNAs in human ES cells assemble into a bona fide RISC that contains Ago2 and can specifically cleave perfectly matched target RNA. Our results demonstrate that human ES cell differentiation is accompanied by changes in the expression of a unique set of miRNAs, providing a glimpse of a new molecular circuitry that may regulate early development in humans. Chromosomes 19 and X contained 98 and 40 miRNA genes, respectively, indicating that majority of miRNA genes in hES cells were expressed from these two chromosomes. Strikingly, distribution analysis of miRNA gene loci across six species including dog, rat, mouse, rhesus, chimpanzee, and human showed that miRNA genes encoded in chromosome 19 were drastically increased in chimpanzees and humans while miRNA gene loci on other chrosmomes were decreased as compared with dog, rat, and mouse. Comparative genomic studies showed 99% conservation of chromosome 19 miRNA genes between chimpanzees and humans. Together, these findings reveal the evolutionary emergence, ∼5 million years ago, of miRNAs involved in regulating early human development. One could imagine that this burst of miRNA gene clusters at specific chromosomes was part of an evolutionary event during species divergence

Regulation of genomic and biobanking research in Africa: a content analysis of ethics guidelines, policies and procedures from 22 African countries

Background: The introduction of genomics and biobanking methodologies to the African research context has also introduced novel ways of doing science, based on values of sharing and reuse of data and samples. This shift raises ethical challenges that need to be considered when research is reviewed by ethics committees, relating for instance to broad consent, the feedback of individual genetic findings, and regulation of secondary sample access and use. Yet existing ethics guidelines and regulations in Africa do not successfully regulate research based on sharing, causing confusion about what is allowed, where and when. Methods: In order to understand better the ethics regulatory landscape around genomic research and biobanking, we conducted a comprehensive analysis of existing ethics guidelines, policies and other similar sources. We sourced 30 ethics regulatory documents from 22 African countries. We used software that assists with qualitative data analysis to conduct a thematic analysis of these documents. Results: Surprisingly considering how contentious broad consent is in Africa, we found that most countries allow the use of this consent model, with its use banned in only three of the countries we investigated. In a likely response to fears about exploitation, the export of samples outside of the continent is strictly regulated, sometimes in conjunction with regulations around international collaboration. We also found that whilst an essential and critical component of ensuring ethical best practice in genomics research relates to the governance framework that accompanies sample and data sharing, this was most sparingly covered in the guidelines. Conclusions: There is a need for ethics guidelines in African countries to be adapted to the changing science policy landscape, which increasingly supports principles of openness, storage, sharing and secondary use. Current guidelines are not pertinent to the ethical challenges that such a new orientation raises, and therefore fail to provide accurate guidance to ethics committees and researchers

Serine phosphorylation regulates paxillin turnover during cell migration

BACKGROUND: Paxillin acts as an adaptor protein that localizes to focal adhesion. This protein is regulated during cell migration by phosphorylation on tyrosine, serine and threonine residues. Most of these phosphorylations have been implicated in the regulation of different steps of cell migration. The two major phosphorylation sites of paxillin in response to adhesion to an extracellular matrix are serines 188 and 190. However, the function of this phosphorylation event remains unknown. The purpose of this work was to determine the role of paxillin phosphorylation on residues S188 and S190 in the regulation of cell migration. RESULTS: We used NBT-II epithelial cells that can be induced to migrate when plated on collagen. To examine the role of paxillin serines 188/190 in cell migration, we constructed an EGFP-tagged paxillin mutant in which S188/S190 were mutated into unphosphorylatable alanine residues. We provide evidence that paxillin is regulated by proteasomal degradation following polyubiquitylation of the protein. During active cell migration on collagen, paxillin is protected from proteasome-dependent degradation. We demonstrate that phosphorylation of serines 188/190 is necessary for the protective effect of collagen. In an effort to understand the physiological relevance of paxillin protection from degradation, we show that cells expressing the paxillin S188/190A interfering mutant spread less, have reduced protrusive activity but migrate more actively. CONCLUSION: Our data demonstrate for the first time that serine-regulated degradation of paxillin plays a key role in the modulation of membrane dynamics and consequently, in the control of cell motility