Efficient coupling of photons to a single molecule and the observation of its resonance fluorescence

Single dye molecules at cryogenic temperatures display many spectroscopic phenomena known from free atoms and are thus promising candidates for fundamental quantum optical studies. However, the existing techniques for the detection of single molecules have either sacrificed the information on the coherence of the excited state or have been inefficient. Here we show that these problems can be addressed by focusing the excitation light near to the absorption cross section of a molecule. Our detection scheme allows us to explore resonance fluorescence over 9 orders of magnitude of excitation intensity and to separate its coherent and incoherent parts. In the strong excitation regime, we demonstrate the first observation of the Mollow triplet from a single solid-state emitter. Under weak excitation we report the detection of a single molecule with an incident power as faint as 150 attoWatt, paving the way for studying nonlinear effects with only a few photons.Comment: 6 figure

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study)

10.1186/1471-2407-12-529BMC Cancer12-BCMA

An automated Raman-based platform for the sorting of live cells by functional properties

Stable-isotope probing is widely used to study the function of microbial taxa in their natural environment, but sorting of isotopically labelled microbial cells from complex samples for subsequent genomic analysis or cultivation is still in its early infancy. Here, we introduce an optofluidic platform for automated sorting of stable-isotope-probing-labelled microbial cells, combining microfluidics, optical tweezing and Raman microspectroscopy, which yields live cells suitable for subsequent single-cell genomics, mini-metagenomics or cultivation. We describe the design and optimization of this Raman-activated cell-sorting approach, illustrate its operation with four model bacteria (two intestinal, one soil and one marine) and demonstrate its high sorting accuracy (98.3 ± 1.7%), throughput (200-500 cells h-1; 3.3-8.3 cells min-1) and compatibility with cultivation. Application of this sorting approach for the metagenomic characterization of bacteria involved in mucin degradation in the mouse colon revealed a diverse consortium of bacteria, including several members of the underexplored family Muribaculaceae, highlighting both the complexity of this niche and the potential of Raman-activated cell sorting for identifying key players in targeted processes.</p

Nontypable Haemophilus influenzae Displays a Prevalent Surface Structure Molecular Pattern in Clinical Isolates

Non-typable Haemophilus influenzae (NTHi) is a Gram negative pathogen that causes acute respiratory infections and is associated with the progression of chronic respiratory diseases. Previous studies have established the existence of a remarkable genetic variability among NTHi strains. In this study we show that, in spite of a high level of genetic heterogeneity, NTHi clinical isolates display a prevalent molecular feature, which could confer fitness during infectious processes. A total of 111 non-isogenic NTHi strains from an identical number of patients, isolated in two distinct geographical locations in the same period of time, were used to analyse nine genes encoding bacterial surface molecules, and revealed the existence of one highly prevalent molecular pattern (lgtF+, lic2A+, lic1D+, lic3A+, lic3B+, siaA−, lic2C+, ompP5+, oapA+) displayed by 94.6% of isolates. Such a genetic profile was associated with a higher bacterial resistance to serum mediated killing and enhanced adherence to human respiratory epithelial cells

Determinants of preventable readmissions in the United States: a systematic review

<p>Abstract</p> <p>Background</p> <p>Hospital readmissions are a leading topic of healthcare policy and practice reform because they are common, costly, and potentially avoidable events. Hospitals face the prospect of reduced or eliminated reimbursement for an increasing number of preventable readmissions under nationwide cost savings and quality improvement efforts. To meet the current changes and future expectations, organizations are looking for potential strategies to reduce readmissions. We undertook a systematic review of the literature to determine what factors are associated with preventable readmissions.</p> <p>Methods</p> <p>We conducted a review of the English language medicine, health, and health services research literature (2000 to 2009) for research studies dealing with unplanned, avoidable, preventable, or early readmissions. Each of these modifying terms was included in keyword searches of readmissions or rehospitalizations in Medline, ISI, CINAHL, The Cochrane Library, ProQuest Health Management, and PAIS International. Results were limited to US adult populations.</p> <p>Results</p> <p>The review included 37 studies with significant variation in index conditions, readmitting conditions, timeframe, and terminology. Studies of cardiovascular-related readmissions were most common, followed by all cause readmissions, other surgical procedures, and other specific-conditions. Patient-level indicators of general ill health or complexity were the commonly identified risk factors. While more than one study demonstrated preventable readmissions vary by hospital, identification of many specific organizational level characteristics was lacking.</p> <p>Conclusions</p> <p>The current literature on preventable readmissions in the US contains evidence from a variety of patient populations, geographical locations, healthcare settings, study designs, clinical and theoretical perspectives, and conditions. However, definitional variations, clear gaps, and methodological challenges limit translation of this literature into guidance for the operation and management of healthcare organizations. We recommend that those organizations that propose to reward reductions in preventable readmissions invest in additional research across multiple hospitals in order to fill this serious gap in knowledge of great potential value to payers, providers, and patients.</p

Induction of beta defensin 2 by NTHi requires TLR2 mediated MyD88 and IRAK-TRAF6-p38MAPK signaling pathway in human middle ear epithelial cells

<p>Abstract</p> <p>Background</p> <p>All mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against various otitis media pathogens. Among the AIIMs, human β-defensin 2 is the most potent molecule and is inducible by exposure to inflammatory stimuli such as bacterial components or proinflammatory cytokines. Even though the β-defensin 2 is an important AIIM, the induction mechanism of this molecule has not been clearly established. We believe that this report is the first attempt to elucidate NTHi induced β-defensin expression in airway mucosa, which includes the middle ear.</p> <p>Methods</p> <p>Monoclonal antibody blocking method was employed in monitoring the TLR-dependent NTHi response. Two gene knock down methods – dominant negative (DN) plasmid and small interfering RNA (siRNA) – were employed to detect and confirm the involvement of several key genes in the signaling cascade resulting from the NTHi stimulated β-defensin 2 expression in human middle ear epithelial cell (HMEEC-1). The student's <it>t</it>-test was used for the statistical analysis of the data.</p> <p>Results</p> <p>The experimental results showed that the major NTHi-specific receptor in HMEEC-1 is the Toll-like receptor 2 (TLR2). Furthermore, recognition of NTHi component(s)/ligand(s) by TLR2, activated the Toll/IL-1 receptor (TIR)-MyD88-IRAK1-TRAF6-MKK3/6-p38 MAPK signal transduction pathway, ultimately leading to the induction of β-defensin 2.</p> <p>Conclusion</p> <p>This study found that the induction of β-defensin 2 is highest in whole cell lysate (WCL) preparations of NTHi, suggesting that the ligand(s) responsible for this up-regulation may be soluble macromolecule(s). We also found that this induction takes place through the TLR2 dependent MyD88-IRAK1-TRAF6-p38 MAPK pathway, with the primary response occurring within the first hour of stimulation. In combination with our previous studies showing that IL-1α-induced β-defensin 2 expression takes place through a MyD88-independent Raf-MEK1/2-ERK MAPK pathway, we found that both signaling cascades act synergistically to up-regulate β-defensin 2 levels. We propose that this confers an essential evolutionary advantage to the cells in coping with infections and may serve to amplify the innate immune response through paracrine signaling.</p

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta