Evidence for erbium-erbium energy migration in erbium(III) bis(perfluoro-p-tolyl)phosphinate

Copyright 2008 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. This article appeared in Applied Physics Letters 92, 103303 (2008) and may be found at

Near IR luminescent rare earth 3,4,5,6-tetrafluoro-2-nitrophenoxide complexes: Synthesis, X-ray crystallography and spectroscopy

NOTICE: this is the author’s version of a work that was accepted for publication in Near IR luminescent rare earth 3,4,5,6-tetrafluoro-2-nitrophenoxide complexes: Synthesis, X-ray crystallography and spectroscopy. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Near IR luminescent rare earth 3,4,5,6-tetrafluoro-2-nitrophenoxide complexes: Synthesis, X-ray crystallography and spectroscopy, [VOL27, ISSUE5, (2008)] DOI: 10.1016/j.poly.2008.01.02

Quenching of Er(III) luminescence by ligand C-H vibrations: Implications for the use of erbium complexes in telecommunications

Copyright 2006 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. This article appeared in Applied Physics Letters 89, 111115 (2006) and may be found at

Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts essential genes and novel targets for antimicrobial development

This is the final version of the article. Available from the publisher via the DOI in this record.Burkholderia pseudomallei is the causative agent of melioidosis, an often fatal infectious disease for which there is no vaccine. B. pseudomallei is listed as a tier 1 select agent, and as current therapeutic options are limited due to its natural resistance to most antibiotics, the development of new antimicrobial therapies is imperative. To identify drug targets and better understand the complex B. pseudomallei genome, we sought a genome-wide approach to identify lethal gene targets. As B. pseudomallei has an unusually large genome spread over two chromosomes, an extensive screen was required to achieve a comprehensive analysis. Here we describe transposon-directed insertion site sequencing (TraDIS) of a library of over 10(6) transposon insertion mutants, which provides the level of genome saturation required to identify essential genes. Using this technique, we have identified a set of 505 genes that are predicted to be essential in B. pseudomallei K96243. To validate our screen, three genes predicted to be essential, pyrH, accA, and sodB, and a gene predicted to be nonessential, bpss0370, were independently investigated through the generation of conditional mutants. The conditional mutants confirmed the TraDIS predictions, showing that we have generated a list of genes predicted to be essential and demonstrating that this technique can be used to analyze complex genomes and thus be more widely applied. IMPORTANCE: Burkholderia pseudomallei is a lethal human pathogen that is considered a potential bioterrorism threat and has limited treatment options due to an unusually high natural resistance to most antibiotics. We have identified a set of genes that are required for bacterial growth and thus are excellent candidates against which to develop potential novel antibiotics. To validate our approach, we constructed four mutants in which gene expression can be turned on and off conditionally to confirm that these genes are required for the bacteria to survive.This work was partially funded by the Defence Science and Technology Laboratories (DSTL)

Risk factors associated with mechanical ventilation, autonomic nervous dysfunction and physical outcome in Vietnamese adults with tetanus.

BACKGROUND: Tetanus remains common in many low- and middle-income countries, but as critical care services improve, mortality from tetanus is improving. Nevertheless, patients develop severe syndromes associated with autonomic nervous system disturbance (ANSD) and the requirement for mechanical ventilation (MV). Understanding factors associated with worse outcome in such settings is important to direct interventions. In this study, we investigate risk factors for disease severity and long-term physical outcome in adults with tetanus admitted to a Vietnamese intensive care unit. METHODS: Clinical and demographic variables were collected prospectively from 180 adults with tetanus. Physical function component scores (PCS), calculated from Short Form Health Survey (SF-36), were assessed in 79 patients at hospital discharge, 3 and 6 months post discharge. RESULTS: Age, temperature, heart rate, lower peripheral oxygen saturation (SpO2) and shorter time from first symptom to admission were associated with MV (OR 1.03 [ 95% confidence interval (CI) 1.00, 1.05], p = 0.04; OR 2.10 [95% CI 1.03, 4.60], p = 0.04; OR 1.04 [ 95% CI 1.01, 1.07], p = 0.02); OR 0.80 [95% CI 0.66, 0.94], p = 0.02 and OR 0.65 [95% CI 0.52, 0.79, p < 0.001, respectively). Heart rate, SpO2 and time from first symptom to admission were associated with ANSD (OR 1.03 [95% CI 1.01, 1.06], p < 0.01; OR 0.95 [95% CI 0.9, 1.00], p = 0.04 and OR 0.64 [95% CI 0.48, 0.80], p < 0.01, respectively). Median [interquartile range] PCS at hospital discharge, 3 and 6 months were 32.37 [24.95-41.57, 53.0 [41.6-56.3] and 54.8 [51.6-57.3], respectively. Age, female sex, admission systolic blood pressure, admission SpO2, MV, ANSD, midazolam requirement, hospital-acquired infection, pressure ulcer and duration of ICU and hospital stay were associated with reduced 0.25 quantile PCS at 6 months after hospital discharge. CONCLUSIONS: MV and ANSD may be suitable endpoints for future research. Risk factors for reduced physical function at 3 months and 6 months post discharge suggest that modifiable features during hospital management are important determinants of long-term outcome

Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al

The Use of a Disclosing Agent During Resective Periodontal Surgery for Improved Removal of Biofilm

A total removal of the bacterial deposits is one of the main challenges of periodontal therapy. A surgical approach is sometimes required in order to allow a correct access to the areas not thoroughly reached during the initial therapy. The present study focuses on the surgical scaling effectiveness in root deposits removal; the potential support of a disclosing agent during this procedure is also evaluated. Forty surgical periodontal patients were randomly divided between surgeries where the operator was informed about a final examination of the residual root deposits and surgeries where the operator was not informed. Straight after scaling procedures a supervisor recorded the O’Leary Plaque Index of the exposed roots by mean of a disclosing agent and the percentage of teeth with residual biofilm. After the stained deposits removal, a second chromatic examination was performed and new data were collected. Mann-Whitney U-test and Wilcoxon test for paired samples were used for comparisons respectively between the two surgery groups and the first and the second chromatic examination; one-sided p-value was set at 0.05. At first examination no significant differences between the two groups were observed regarding Plaque Index (p=0.24) and percentages of teeth with residual biofilm (p=0.07). The 100% removal of roots deposits was never achieved during the study but a significant reduction of 80% of root deposits was observed between first and second examination (p=0.0001). Since root deposits removal during periodontal surgery resulted always suboptimal, the use of a disclosing agent during this procedure could be a useful and practical aid

Chronic multichannel neural recordings from soft regenerative microchannel electrodes during gait

Reliably interfacing a nerve with an electrode array is one of the approaches to restore motor and sensory functions after an injury to the peripheral nerve. Accomplishing this with current technologies is challenging as the electrode-neuron interface often degrades over time, and surrounding myoelectric signals contaminate the neuro-signals in awake, moving animals. The purpose of this study was to evaluate the potential of microchannel electrode implants to monitor over time and in freely moving animals, neural activity from regenerating nerves. We designed and fabricated implants with silicone rubber and elastic thin-film metallization. Each implant carries an eight-by-twelve matrix of parallel microchannels (of 120\u2009 7\u2009110\u2009\u3bcm2 cross-section and 4\u2009mm length) and gold thin-film electrodes embedded in the floor of ten of the microchannels. After sterilization, the soft, multi-lumen electrode implant is sutured between the stumps of the sciatic nerve. Over a period of three months and in four rats, the microchannel electrodes recorded spike activity from the regenerating sciatic nerve. Histology indicates mini-nerves formed of axons and supporting cells regenerate robustly in the implants. Analysis of the recorded spikes and gait kinematics over the ten-week period suggests firing patterns collected with the microchannel electrode implant can be associated with different phases of gait

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy