Perturbation spectroscopy of the argon ion laser

The technique of perturbation spectroscopy has been applied to study the argon ion laser discharge. In this technique the laser radiation field present within the active medium is switched on and off, and this modulates the population of the upper laser level. By studying the magnitude of these modulations as discharge conditions within the active medium are changed, the copulation inversions on the 4p2D5/2 - 4s2P3/2 and 4p4D5/2 - 4s2P3/2 laser transitions have been explored. By studying, in the presence of an applied magnetic field, the polarization induced in the spontaneous emission sidelight through these modulations, the lifetime of the 4p2D5/2 upper laser level has been estimated. By studying the population changes induced on other 4p and 4d levels as a consequence of the population change on the upper laser level, the relative importance of various proposed excitation mechanisms for the 4p upper laser levels have been assessed. The population inversions (1 - g1N2/g2N1, where N1 is the population of the upper laser level and N2. the population of the lower laser level) on the 4p2D5/2 - 4s2P3/2 and 4p4D5/2 - 4s2P3/2 transitions of Ar II are destroyed by increasing the argon pressure above 0.2 - 0.3 Torr, and for higher pressures the medium exhibits absorption. Both population inversions increase slowly with discharge current. By using a flow graph technique to analyse the population inversions, this latter is shown to imply that the electron temperature in the discharge increases with current. The polarization experiments have been analysed by both a simple rate equation treatment, and by a more complete approach based on Lamb theory. This latter treatment demonstrates that the dependence of polarization ratio on magnetic field can be used to determine the lifetime of the upper laser level. Polarization ratios on the 4p2D5/2 - 4s2P3/2 and 4p4D5/2 - 4s2P3/2 transitions have been measured as a function of discharge parameters and applied axial magnetic field. From the variation of polarization ratio with magnetic field, the lifetime of the 4p2D5/2 level of Ar II under discharge conditions has been estimated. The perturbations in the populations of other 4p and 4d levels of Ar II resulting from the modulation of the upper laser level have been measured as a function of discharge parameters. Their magnitudes and dependence on discharge current provide direct evidence that an important excitation pathway for the 4p upper laser levels of Ar II is step wise excitation through the quartet 4s levels of Ar II

Widely-tunable mid-infrared ring cavity pump-enhanced OPO and application in photo-thermal interferometric trace ethane detection

Funding: Innovate UK (133076); Engineering and Physical Sciences Research Council (EP//L01596X/1, EP/M01326X/1, EP/M024385/1); European Research Council (ERC-2018-STG 803665).The development of a broadly and accurately tunable single-frequency mid-infrared laser source and its application to a sensitive laser absorption detection method are described. Photo-thermal interferometric spectroscopy is employed as a phase-sensitive method to detect the minute refractive index change caused by the heating of a gas under laser radiation. A separate probe beam allows for the spectrally-interesting mid-infrared region to be examined whilst utilizing low cost, high detectivity photodetectors in the visible/near-infrared region. We also describe the implementation of a Sagnac interferometer to minimize the effects of environmental perturbation and provide inherent passive stability. A continuous-wave ring-cavity pump-enhanced OPO has been developed to provide excitation light from 3–4 µm at 140 mW with the ability to mode-hop tune continuously over 90 cm−1 in 0.07 cm−1 steps. Complementary use of both detection apparatus and excitation source has allowed for presence of ethane to be detected down to 200 parts per billion.developed to provide excitation light from 3–4 µm at 140 mW with the ability to mode-hop tune continuously over 90 cm−1 in 0.07 cm−1 steps. Complementary use of both detection apparatus and excitation source has allowed for presence of ethane to be detected down to 200 parts per billion.Publisher PDFPeer reviewe

The experience of linking Victorian emergency medical service trauma data

<p>Abstract</p> <p>Background</p> <p>The linking of a large Emergency Medical Service (EMS) dataset with the Victorian Department of Human Services (DHS) hospital datasets and Victorian State Trauma Outcome Registry and Monitoring (VSTORM) dataset to determine patient outcomes has not previously been undertaken in Victoria. The objective of this study was to identify the linkage rate of a large EMS trauma dataset with the Department of Human Services hospital datasets and VSTORM dataset.</p> <p>Methods</p> <p>The linking of an EMS trauma dataset to the hospital datasets utilised deterministic and probabilistic matching. The linking of three EMS trauma datasets to the VSTORM dataset utilised deterministic, probabilistic and manual matching.</p> <p>Results</p> <p>There were 66.7% of patients from the EMS dataset located in the VEMD. There were 96% of patients located in the VAED who were defined in the VEMD as being admitted to hospital. 3.7% of patients located in the VAED could not be found in the VEMD due to hospitals not reporting to the VEMD. For the EMS datasets, there was a 146% increase in successful links with the trauma profile dataset, a 221% increase in successful links with the mechanism of injury only dataset, and a 46% increase with sudden deterioration dataset, to VSTORM when using manual compared to deterministic matching.</p> <p>Conclusion</p> <p>This study has demonstrated that EMS data can be successfully linked to other health related datasets using deterministic and probabilistic matching with varying levels of success. The quality of EMS data needs to be improved to ensure better linkage success rates with other health related datasets.</p

2016 AAPP Monograph Series: African American Professors Program

The African American Professors Program (AAPP) at the University of South Carolina is honored to publish this fifteenth edition of its annual monograph series. AAPP recognizes the significance of offering scholars a venue through which to engage actively in research and to publish their refereed papers. Parallel with the publication of their manuscripts is the opportunity to gain visibility among colleagues throughout postsecondary institutions at national and international levels. Scholars who have contributed papers for this monograph are acknowledged for embracing the value of including this responsibility within their academic milieu. Writing across disciplines adds to the intellectual diversity of these manuscripts. From neophytes to quite experienced individuals, the chapters have been researched and written in depth. Founded in 1997 through the Department of Educational Leadership and Policies in the College of Education, AAPP was designed originally to address the under-representation of African American professors on college and university campuses. Its mission is to expand the pool of these professors in critical academic and research areas. Sponsored historically by the University of South Carolina, the W.K. Kellogg Foundation, and the South Carolina General Assembly, the program recruits doctoral students for disciplines in which African Americans currently are underrepresented among faculty in higher education. The continuation of this monograph series is seen as responding to a window of opportunity to be sensitive to academic expectation of graduates as they pursue career placement and, at the same time, to allow for the dissemination of products of scholarship to a broader community. The importance of this series has been voiced by one of our 2002 AAPP graduates, Dr. Shundelle LaTjuan Dogan, formerly an Administrative Fellow at Harvard University, a Program Officer for the Southern Education Foundation, and a Program Officer for the Arthur M. Blank Foundation in Atlanta, Georgia. She is currently a Corporate Citizenship and Corporate Affairs Manager for IBM-International Business Machines in Atlanta, Georgia and has written the Foreword for the 2014 monograph. Dr. Dogan wrote: One thing in particular that I want to thank you for is having the African American Professors Program scholars publish articles for the monograph. I have to admit that writing the articles seemed like extra work at the time. However, in my recent interview process, organizations have asked me for samples of my writing. Including an article from a published monograph helped to make my portfolio much more impressive. You were \u27right on target\u27 in having us do the monograph series. (AAPP 2003 Monograph, p. xi) The African American Professors Program continues the tradition as a promoter of international scholarship in higher education evidenced through the inspiration from this group of interdisciplinary manuscripts. I hope that you will envision these published papers to serve as an invaluable contribution to your own professional development and career enhancement. John McFadden, PhD The Benjamin Elijah Mays Distinguished Professor Emeritus Director, African American Professors Program University of South Carolinahttps://scholarcommons.sc.edu/mcfadden_monographs/1003/thumbnail.jp

How to find simple and accurate rules for viral protease cleavage specificities

<p>Abstract</p> <p>Background</p> <p>Proteases of human pathogens are becoming increasingly important drug targets, hence it is necessary to understand their substrate specificity and to interpret this knowledge in practically useful ways. New methods are being developed that produce large amounts of cleavage information for individual proteases and some have been applied to extract cleavage rules from data. However, the hitherto proposed methods for extracting rules have been neither easy to understand nor very accurate. To be practically useful, cleavage rules should be accurate, compact, and expressed in an easily understandable way.</p> <p>Results</p> <p>A new method is presented for producing cleavage rules for viral proteases with seemingly complex cleavage profiles. The method is based on orthogonal search-based rule extraction (OSRE) combined with spectral clustering. It is demonstrated on substrate data sets for human immunodeficiency virus type 1 (HIV-1) protease and hepatitis C (HCV) NS3/4A protease, showing excellent prediction performance for both HIV-1 cleavage and HCV NS3/4A cleavage, agreeing with observed HCV genotype differences. New cleavage rules (consensus sequences) are suggested for HIV-1 and HCV NS3/4A cleavages. The practical usability of the method is also demonstrated by using it to predict the location of an internal cleavage site in the HCV NS3 protease and to correct the location of a previously reported internal cleavage site in the HCV NS3 protease. The method is fast to converge and yields accurate rules, on par with previous results for HIV-1 protease and better than previous state-of-the-art for HCV NS3/4A protease. Moreover, the rules are fewer and simpler than previously obtained with rule extraction methods.</p> <p>Conclusion</p> <p>A rule extraction methodology by searching for multivariate low-order predicates yields results that significantly outperform existing rule bases on out-of-sample data, but are more transparent to expert users. The approach yields rules that are easy to use and useful for interpreting experimental data.</p

Breast epithelial cell proliferation is markedly increased with short-term high levels of endogenous estrogen secondary to controlled ovarian hyperstimulation

Oocyte donors have high serum estradiol (E2) levels similar to the serum levels seen in the first trimester of pregnancy. We report in this article our studies comparing cell proliferation, Ki67 (MIB1), and estrogen and progesterone receptor levels (ERα, PRA, and PRB) in the breast terminal duct lobular units of oocyte donors, women in early pregnancy, and in normally cycling women. Breast tissue and blood samples were obtained from 10 oocyte donors, and 30 pregnant women at 5–18 weeks of gestation. Breast tissue samples were also obtained from 26 normally cycling women. In the oocyte donors: peak E2 (mean ~15,300 pmol/l) was reached on the day before oocyte (and tissue) donation; peak progesterone (P4; mean 36.3 nmol/l) was reached on the day of donation; Ki67 was positively associated with level of E2, and the mean Ki67 was 7.0% significantly greater than the mean 1.8% of cycling women. In the pregnant women: mean E2 rose from ~2,000 pmol/l at 5 weeks of gestation to ~27,000 pmol/l at 18 weeks; mean P4 did not change from ~40 nmol/l until around gestational week 11 when it increased to ~80 nmol/l; mean Ki67 was 15.4% and did not vary with gestational age or E2. Oocyte donors have greatly increased levels of E2 and of breast-cell proliferation, both comparable in the majority of donors to the levels seen in the first trimester of pregnancy. Whether their short durations of greatly increased E2 levels are associated with any long-term beneficial effects on the breast, as occurring in rodent models, is not known

A Regulatory Role for NBS1 in Strand-Specific Mutagenesis during Somatic Hypermutation

Activation-induced cytidine deaminase (AID) is believed to initiate somatic hypermutation (SHM) by deamination of deoxycytidines to deoxyuridines within the immunoglobulin variable regions genes. The deaminated bases can subsequently be replicated over, processed by base excision repair or mismatch repair, leading to introduction of different types of point mutations (G/C transitions, G/C transversions and A/T mutations). It is evident that the base excision repair pathway is largely dependent on uracil-DNA glycosylase (UNG) through its uracil excision activity. It is not known, however, which endonuclease acts in the step immediately downstream of UNG, i.e. that cleaves at the abasic sites generated by the latter. Two candidates have been proposed, an apurinic/apyrimidinic endonuclease (APE) and the Mre11-Rad50-NBS1 complex. The latter is intriguing as this might explain how the mutagenic pathway is primed during SHM. We have investigated the latter possibility by studying the in vivo SHM pattern in B cells from ataxia-telangiectasia-like disorder (Mre11 deficient) and Nijmegen breakage syndrome (NBS1 deficient) patients. Our results show that, although the pattern of mutations in the variable heavy chain (VH) genes was altered in NBS1 deficient patients, with a significantly increased number of G (but not C) transversions occurring in the SHM and/or AID targeting hotspots, the general pattern of mutations in the VH genes in Mre11 deficient patients was only slightly altered, with an increased frequency of A to C transversions. The Mre11-Rad50-NBS1 complex is thus unlikely to be the major nuclease involved in cleavage of the abasic sites during SHM, whereas NBS1 might have a specific role in regulating the strand-biased repair during phase Ib mutagenesis

SNAGA, TEORIJA I PRAKSA (Kraft, Theorie und Praxis)

We have developed a global biogeographic classification of the mesopelagic zone to reflect the regional scales over which the ocean interior varies in terms of biodiversity and function. An integrated approach was necessary, as global gaps in information and variable sampling methods preclude strictly statistical approaches. A panel combining expertise in oceanography, geospatial mapping, and deep-sea biology convened to collate expert opinion on the distributional patterns of pelagic fauna relative to environmental proxies (temperature, salinity, and dissolved oxygen at mesopelagic depths). An iterative Delphi Method integrating additional biological and physical data was used to classify biogeographic ecoregions and to identify the location of ecoregion boundaries or inter-regions gradients. We define 33 global mesopelagic ecoregions. Of these, 20 are oceanic while 13 are ‘distant neritic.’ While each is driven by a complex of controlling factors, the putative primary driver of each ecoregion was identified. While work remains to be done to produce a comprehensive and robust mesopelagic biogeography (i.e., reflecting temporal variation), we believe that the classification set forth in this study will prove to be a useful and timely input to policy planning and management for conservation of deep-pelagic marine resources. In particular, it gives an indication of the spatial scale at which faunal communities are expected to be broadly similar in composition, and hence can inform application of ecosystem-based management approaches, marine spatial planning and the distribution and spacing of networks of representative protected areas

A transcriptomic analysis of Echinococcus granulosus larval stages:implications for parasite biology and host adaptation

The cestode Echinococcus granulosus--the agent of cystic echinococcosis, a zoonosis affecting humans and domestic animals worldwide--is an excellent model for the study of host-parasite cross-talk that interfaces with two mammalian hosts. To develop the molecular analysis of these interactions, we carried out an EST survey of E. granulosus larval stages. We report the salient features of this study with a focus on genes reflecting physiological adaptations of different parasite stages.We generated ~10,000 ESTs from two sets of full-length enriched libraries (derived from oligo-capped and trans-spliced cDNAs) prepared with three parasite materials: hydatid cyst wall, larval worms (protoscoleces), and pepsin/H(+)-activated protoscoleces. The ESTs were clustered into 2700 distinct gene products. In the context of the biology of E. granulosus, our analyses reveal: (i) a diverse group of abundant long non-protein coding transcripts showing homology to a middle repetitive element (EgBRep) that could either be active molecular species or represent precursors of small RNAs (like piRNAs); (ii) an up-regulation of fermentative pathways in the tissue of the cyst wall; (iii) highly expressed thiol- and selenol-dependent antioxidant enzyme targets of thioredoxin glutathione reductase, the functional hub of redox metabolism in parasitic flatworms; (iv) candidate apomucins for the external layer of the tissue-dwelling hydatid cyst, a mucin-rich structure that is critical for survival in the intermediate host; (v) a set of tetraspanins, a protein family that appears to have expanded in the cestode lineage; and (vi) a set of platyhelminth-specific gene products that may offer targets for novel pan-platyhelminth drug development.This survey has greatly increased the quality and the quantity of the molecular information on E. granulosus and constitutes a valuable resource for gene prediction on the parasite genome and for further genomic and proteomic analyses focused on cestodes and platyhelminths

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation