Long-wave infrared pulsed external-cavity QCL spectrometer using a hollow waveguide gas cell.

A spectrometer built using an external cavity pulsed quantum cascade laser is described. The spectrometer has a tuning range from 10 - 13 µm (1,000 - 769 cm-1) and is designed to target volatile organic compounds (VOCs) which often exhibit water-free molecular absorption within the region. The spectrometer utilizes a hollow silica waveguide gas cell which has an internal volume of a few millilitres, a fast response time (∼1 s), and is advantageous when only low sample volumes, similar to the cell volume, are available. Propane is used as a test gas because it is easy to handle, and its spectral profile is comparable to VOCs of interest. Its absorption in the region is primarily within the ν21 band which spans from 10.55 - 11.16 µm (948 - 896 cm-1). Spectral measurements at a range of concentrations show good linearity and an Allan deviation of absorbance values recorded over a 100-minute period indicates a minimum detectable absorbance of 3.5×10-5 at an integration time of 75 s.

Algorithm-driven activity-directed expansion of a series of antibacterial quinazolinones.

Activity-directed synthesis (ADS) is a structure-blind, function driven approach that can drive the discovery of bioactive small molecules. In ADS, arrays of reactions are designed and executed, and the crude product mixtures are then directly screened to identify reactions that yield bioactive products. The design of subsequent reaction arrays is then informed by the hit reactions that are discovered. In this study, algorithms for reaction array design were developed in which the reactions to be executed were selected from a large set of virtual reactions; the reactions were selected on the basis of similarity to reactions known to yield bioactive products. The algorithms were harnessed to design arrays of photoredox-catalysed alkylation reactions whose crude products were then screened for inhibition of growth of S. aureus ATCC29213. It was demonstrated that the approach enabled expansion of a series of antibacterial quinazolinones. It is envisaged that such algorithms could ultimately enable fully autonomous activity-directed molecular discovery.

Late-Onset Metastatic Renal Cell Carcinoma to the Thyroid Gland: An Unusual Airway Emergency.

BACKGROUND Thyroid malignant lesions mostly present as an anterior neck mass with or without compressive symptoms. Infrequently, metastases from extra-thyroid neoplasms migrate to the thyroid gland. These lesions most commonly arise from renal cell carcinoma (RCC), which is the primary kidney malignancy in adults. This case parallels one of the longest latency periods described in the literature from a primary RCC with metastasis to the thyroid gland (TG). CASE REPORT We report a case of an 88-year-old female patient with past medical history of RCC resected 25 years earlier, who presented to the Emergency Department with a large left anterior neck mass causing dyspnea and stridor due to intra-tracheal extension. The airway symptoms progressed rapidly, and she required emergent management to secure the airway in the operating room. CONCLUSIONS This case reports a rare instance in which RCC metastasis presented with intra-tracheal extension causing airway compromise and the need for emergent airway management. It is the first time that use of cold instruments has been documented to excise RCC's intra-luminal tracheal lesion to secure the airway in an emergent case in a safe manner. With this surgical approach, the airway is secured by endotracheal intubation after excision of an intra-luminal tracheal lesion, with the benefit of avoiding awake tracheostomy in a patient with a distorted neck anatomy. Also, this case reinforces that metastatic RCC to the thyroid gland can occur 25 years after initial diagnosis. For this reason, we advocate lifelong monitoring in patients with the diagnosis of RCC.

Ebullition enhances chemical mass transport across the tailings-water interface of oil sands pit lakes.

Base Mine Lake (BML) was the first commercial-scale demonstration oil sands pit lake established in northern Alberta, Canada. Recent studies indicate that ebullition enhances internal mass loading of dissolved constituents during settlement and dewatering of methanogenic fluid fine tailings (FFT) below the overlying water cap. Here, we describe results of integrated field measurements and numerical modelling to (i) determine potential for ebullition and enhanced mixing within BML, and (ii) assess impacts on chemical mass transport across the tailings-water interface. We observed sharp increases in [CH4(aq)] with depth from <0.1 mg L-1 immediately above the interface to >60 mg L-1 over the upper 1.5 to 3.0 m of FTT. Thermodynamic modelling revealed that maximum [CH4(aq)] values represent 60 to 80% of theoretical saturation, and corresponding total dissolved gas pressures approach or exceed fluid pressures. These findings supported integration of enhanced mixing into one-dimensional (1-D) advective-dispersive transport models, which substantially improved upon previous simulations of conservative tracer (i.e., Cl-) profiles and chemical mass fluxes. The models revealed a positive relationship between CH4(aq) saturation and enhanced mixing, showing that ebullition enhances internal mass loading. This information has potential to inform ongoing assessments of pit lake performance and support improved closure and reclamation planning at oil sands mines.

Discovery, characterization and engineering of ligases for amide synthesis.

Coronatine and related bacterial phytotoxins are mimics of the hormone jasmonyl-L-isoleucine (JA-Ile), which mediates physiologically important plant signalling pathways1-4. Coronatine-like phytotoxins disrupt these essential pathways and have potential in the development of safer, more selective herbicides. Although the biosynthesis of coronatine has been investigated previously, the nature of the enzyme that catalyses the crucial coupling of coronafacic acid to amino acids remains unknown1,2. Here we characterize a family of enzymes, coronafacic acid ligases (CfaLs), and resolve their structures. We found that CfaL can also produce JA-Ile, despite low similarity with the Jar1 enzyme that is responsible for ligation of JA and L-Ile in plants5. This suggests that Jar1 and CfaL evolved independently to catalyse similar reactions-Jar1 producing a compound essential for plant development4,5, and the bacterial ligases producing analogues toxic to plants. We further demonstrate how CfaL enzymes can be used to synthesize a diverse array of amides, obviating the need for protecting groups. Highly selective kinetic resolutions of racemic donor or acceptor substrates were achieved, affording homochiral products. We also used structure-guided mutagenesis to engineer improved CfaL variants. Together, these results show that CfaLs can deliver a wide range of amides for agrochemical, pharmaceutical and other applications.

Some fixed point theorems for mappings satisfying rational inequality in modular metric spaces with applications.

We prove some theorems on the existence and uniqueness of fixed point for Reich-type contraction mappings and Geraghty-type mappings satisfying rational inequalities in modular metric spaces. Our results include the results of [1] and [2] as special cases. Furthermore, we apply our main results in proving the existence and uniqueness of solution of nonlinear Barbashin-type integrodifferential equation satisfying a given initial value problem in modular metric space X ω .

Synthesis of ß-Diamine Building Blocks by Photocatalytic Hydroamination of Enecarbamates with Amines, Ammonia and N-H Heterocycles.

3-Amino-substituted saturated nitrogen heterocycles are an important subclass of ß-diamines, appearing in a number of clinical agents. Herein, we report a unified approach to these products based upon the regioselective photoredox-mediated hydroamination of enecarbamates. The amine coupling partner can encompass diverse amine types under a single set of reaction conditions, including primary alkyl amines, ammonia, aryl and heteroaryl amines, and N-H heterocycles. The method enables the synthesis of a wide range of pharmaceutically relevant building blocks.

Identification of focus areas for Australian Bat Lyssavirus potential exposure prevention in the Metro North Hospital and Health Service region.

Australian Bat Lyssavirus (ABLV) is a fatal rabies-like disease spread to humans from bats. All people who report bat bites or scratches in Queensland are considered potentially exposed to ABLV and are followed up and treated to prevent ABLV. Preventing members of the public intentionally interacting with bats will reduce the number of potential exposures to ABLV. In order to target public health messaging, this study examines the epidemiology of potential ABLV exposures in Metro North Hospital and Health Service (HHS), a region of Queensland that encompasses metro and rural areas in the south-east of the state. People who intentionally handled bats during the study period were more likely to be adult (93%), male (60%), scratched (51%) by a megabat (72%) and been potentially exposed while rescuing the bat when it was trapped or injured (72%). The number of potential exposures reported in Queensland has increased since 2013; the same year, a Queensland child died of ABLV. Seasonally, exposures are more common during bat breeding and nursing periods when bats are more active (summer to autumn). Although there were more notifications in a band stretching north from the inner city to northern metro suburbs, notification rates were higher in large rural statistical areas in the north of the HHS. These data will be used to develop geographically targeted ABLV prevention messaging for the general public.

Instrumentation for quantitative analysis of volatile compounds emission at elevated temperatures. Part 2: Analysis of carbon fibre reinforced epoxy composite.

We have investigated the release of gases and volatile organic compounds (VOCs) from a carbon fibre reinforced epoxy composite matrix used in aircraft structural components. Analysis was performed at several temperatures both up to and above the recommended operating temperature (121 °C) for the material, to a maximum of 250 °C. Gas chromatography-mass spectrometry (GC-MS) combined with thermal desorption (TD-GC-MS) was used to identify and quantify VOCs, and in parallel real-time gas detection with commercial off-the-shelf (COTS) gas sensors. Under hydrocarbon free air, CO, SO2, NO, NO2 and VOCs (mainly aldehydes, ketones and a carboxylic acid) were detected as the gaseous products released during the thermal exposure of the material up to 250 °C, accompanied by increased relative humidity (4%). At temperatures up to 150 °C, gas and volatile emission was limited.

Instrumentation for quantitative analysis of volatile compounds emission at elevated temperatures. Part 1: Design and implementation.

A novel suite of instrumentation for the characterisation of materials held inside an air-tight tube furnace operated up to 250 °C has been developed. Real-time detection of released gases (volatile organic compounds (VOCs), CO2, NO, NO2, SO2, CO and O2) was achieved combining commercial off-the-shelf (COTS) gas sensors and sorbent tubes for further qualitative and semi-quantitative analysis by gas chromatography-mass spectrometry coupled to thermal desorption (TD-GC-MS). The test system was designed to provide a controlled flow (1000 cm3 min-1) of hydrocarbon free air through the furnace. The furnace temperature ramp was set at a rate of 5 °C min-1 with 10 min dwell points at 70 °C, 150 °C, 200 °C and 250 °C to allow time for stabilisation and further headspace sampling onto sorbent tubes. Experimental design of the instrumentation is described here and an example data set upon exposure to a gas sample is presented.

Influence of aberrations on confocal-based remote refractive index measurements.

Confocal scanning combined with low-coherence interferometry is used to provide remote refractive index and thickness measurements of transparent materials. The influence of lens aberrations in the confocal measurement is assessed through ray-trace modeling of the axial point-spread functions generated using optical configurations comprised of paired aspherics and paired achromats. Off-axis parabolic mirrors are suggested as an alternative to lenses and are shown to exhibit much more symmetric profiles provided the system numerical aperture is not too high. The modeled results compare favorably with experimental data generated using an optical instrument comprised of a broadband source and line-scan spectrometer. Refractive index and thickness measurements are made with each configuration with most mirror pairings offering better than twice the repeatability and accuracy of either lens pairing.

A trans-Acting Cyclase Offloading Strategy for Nonribosomal Peptide Synthetases.

The terminal step in the biosynthesis of nonribosomal peptides is the hydrolytic release and, frequently, macrocyclization of an aminoacyl-S-thioester by an embedded thioesterase. The surugamide biosynthetic pathway is composed of two nonribosomal peptide synthetase (NRPS) assembly lines in which one produces surugamide A, which is a cyclic octapeptide, and the other produces surugamide F, a linear decapeptide. The terminal module of each system lacks an embedded thioesterase, which led us to question how the peptides are released from the assembly line (and cyclized in the case of surugamide A). We characterized a cyclase belonging to the ß-lactamase superfamily in vivo, established that it is a trans-acting release factor for both compounds, and verified this functionality in vitro with a thioester mimic of linear surugamide A. Using bioinformatics, we estimate that ∼11% of filamentous Actinobacteria harbor an NRPS system lacking an embedded thioesterase and instead employ a trans-acting cyclase. This study improves the paradigmatic understanding of how nonribosomal peptides are released from the terminal peptidyl carrier protein and adds a new dimension to the synthetic biology toolkit.

Análisis biomecánico en la marcha deportiva entre deportistas de iniciación y alto rendimiento / Biomechanical analysis in sports walk among beginners and high performance athletes

Introducción: La relación causa / efecto entre el embarazo y la enfermedad periodontal resulta muy contradictorio en la literatura. Algunos autores niegan que exista esta relación, mientras otros la afirman. Objetivo: Identificar la presencia de Enfermedad Periodontal en gestantes del primer y tercer trimestre, teniendo en cuenta la edad y la higiene bucal de las mismas. Métodos: La muestra estuvo integrada por 106 gestantes del primer y tercer trimestre del embarazo. Las mismas fueron reunidas de acuerdo a los siguientes grupos de edades: Adolescentes, adultas jóvenes y adultas de más de 35 años. A todas las gestantes de la muestra se les efectuó un examen estomatológico para diagnosticar las pacientes portadoras de Enfermedad Periodontal, las formas clínicas presentadas, así como evaluar la calidad de la higiene bucal. Resultados: Se comprobó que 36 de las gestantes eran portadoras de Enfermedad Periodontal: 34 presentaban gingivitis y dos periodontitis. La forma clínica más abundante fue la gingivitis fibro-edematosa. De las 36 gestantes enfermas, 33 eran adultas jóvenes y tres, mayores de 35 años. Ninguna de las adolescentes presentó EP. Del total de gestantes, 20 se encontraban en el primer trimestre y 16 en el tercero. De las 36 pacientes enfermas 29 presentaron higiene bucal deficiente para un 80,55 por ciento y sólo siete mostraban una higiene bucal eficiente para un 19,44 por ciento. Conclusiones: La Enfermedad Periodontal es frecuente entre las gestantes del primer y tercer trimestre a lo cual contribuye la mala higiene bucal, la edad, como también la elevación de las hormonas durante el embarazo(AU)

Introduction: The cause / effect relationship between pregnancy and periodontal disease is very contradictory in the literature. Some authors deny that this relationship exists, while others affirm it. Objective: To identify the presence of Periodontal Disease in first and third trimester pregnant women, taking into account their age and oral hygiene. Methods: The sample consisted of 106 pregnant women from the first and third trimesters of pregnancy. They were collected according to the following age groups: Adolescents, young adults and adults over 35 years of age. All the pregnant women in the sample underwent a stomatological examination to diagnose the patients carrying Periodontal Disease, the presented clinical forms, as well as to evaluate the quality of the oral hygiene. Results: It was found that 36 of the pregnant women were carriers of Periodontal Disease: 34 had gingivitis and two periodontitis. The most abundant clinical form was fibro-edematous gingivitis. Of the 36 pregnant women, 33 were young adults and three were over 35 years old. None of the adolescents presented EP. Of the total of pregnant women, 20 were in the first quarter and 16 in the third. Of the 36 sick patients, 29 had poor oral hygiene for 80.55 percent and only seven showed efficient oral hygiene for 19.44 percent. Conclusions: Periodontal disease is common among pregnant the first and third quarter which contributes to poor oral hygiene, age, as well as elevated hormones during pregnancy(AU)

De novo Biosynthesis of "Non-Natural" Thaxtomin Phytotoxins.

Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from S. scabies, along with genes encoding a promiscuous tryptophan synthase (TrpS) from Salmonella typhimurium, were assembled in a heterologous host Streptomyces albus. Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to "non-natural" product target compounds.

Capturing the multifactorial nature of ARDS - "Two-hit" approach to model murine acute lung injury.

Severe acute respiratory distress syndrome (ARDS) presents typically with an initializing event, followed by the need for mechanical ventilation. Most animal models of ALI are limited by the fact that they focus on a singular cause of acute lung injury (ALI) and therefore fail to mimic the complex, multifactorial pathobiology of ARDS. To better capture this scenario, we provide a comprehensive characterization of models of ALI combining two injuries: intra tracheal (i.t.) instillation of LPS or hypochloric acid (HCl) followed by ventilator-induced lung injury (VILI). We hypothesized, that mice pretreated with LPS or HCl prior to VILI and thus receiving a ("two-hit injury") will sustain a superadditive lung injury when compared to VILI. Mice were allocated to following treatment groups: control with i.t. NaCl, ventilation with low peak inspiratory pressure (PIP), i.t. HCl, i.t. LPS, VILI (high PIP), HCl i.t. followed by VILI and LPS i.t. followed by VILI. Severity of injury was determined by protein content and MPO activity in bronchoalveolar lavage (BAL), the expression of inflammatory cytokines and histopathology. Mice subjected to VILI after HCl or LPS instillation displayed augmented lung injury, compared to singular lung injury. However, mice that received i.t. LPS prior to VILI showed significantly increased inflammatory lung injury compared to animals that underwent i.t. HCl followed by VILI. The two-hit lung injury models described, resulting in additive but differential acute lung injury recaptures the clinical relevant multifactorial etiology of ALI and could be a valuable tool in translational research.

Spectrometer-based refractive index and dispersion measurement using low-coherence interferometry with confocal scanning.

This paper describes a technique for measuring refractive index and thickness of transparent plates using a fibre-optic low-coherence interferometer. The interferometer is used to independently measure quantities related to the phase and group refractive indices, np and ng, of the material under investigation. Additionally, the dispersion of the phase index dependent quantity is measured by taking advantage of the range of wavelengths available from a broadband source. These three quantities are related to simultaneously yield np and ng as well as the geometrical thickness t of the sample. Measurements are presented for a range of transparent materials including measurements of the ordinary and extraordinary refractive indices of a birefringent sapphire window. The mean percentage errors across all the samples tested were 0.09% for np, 0.08% for np, and 0.11% for t.

Radial Glia Cells Control Angiogenesis in the Developing Cerebral Cortex Through TGF-ß1 Signaling.

Neuroangiogenesis in the developing central nervous system is controlled by interactions between endothelial cells (ECs) and radial glia (RG) neural stem cells, although RG-derived molecules implicated in these events are not fully known. Here, we investigated the role of RG-secreted TGF-ß1, in angiogenesis in the developing cerebral cortex. By isolation of murine microcapillary brain endothelial cells (MBECs), we demonstrate that conditioned medium from RG cultures (RG-CM) promoted MBEC migration and formation of vessel-like structures in vitro, in a TGF-ß1-dependent manner. These events were followed by endothelial regulation of GPR124 and BAI-1 gene expression by RG-CM. Proteome profile of RG-CM identified angiogenesis-related molecules IGFBP2/3, osteopontin, endostatin, SDF1, fractalkine, TIMP1/4, Ang-1, pentraxin3, and Cyr61, some of them modulated by TGF-ß1 induction. In vivo gain and loss of function assays targeting RG cells demonstrates a specific TGF-ß1-dependent control of blood vessels branching in the cerebral cortex. Together, our results point to TGF-ß1 signaling pathway as a potential mediator of the RG-EC interactions and shed light to the key role of RG in paving the brain vascular network.

A Mock Randomized Controlled Trial With Audience Response Technology for Teaching and Learning Epidemiology.

The study's objective was to apply and assess an active learning approach to epidemiology and critical appraisal. Active learning comprised a mock, randomized controlled trial (RCT) conducted with learners in 3 countries. The mock trial consisted of blindly eating red Smarties candy (intervention) compared to yellow Smarties (control) to determine whether red Smarties increase happiness. Audience response devices were employed with the 3-fold purposes to produce outcome data for analysis of the effects of red Smarties, identify baseline and subsequent changes in participant's knowledge and confidence in understanding of RCTs, and assess the teaching approach. Of those attending, 82% (117 of 143 learners) participated in the trial component. Participating in the mock trial was a positive experience, and the use of the technology aided learning. The trial produced data that learners analyzed in "real time" during the class. The mock RCT is a fun and engaging approach to teaching RCTs and helping students to develop skills in critical appraisal.

Interventions for preventing elder abuse: applying findings of a new Cochrane review.

There is evidence that elder abuse is a significant public health problem that is destined to grow as population age. Countries are considering how best to act and this requires an understanding of the complex causal mechanisms contributing to its occurrence and the identification of effective interventions which can potentially make a difference. Previously, a high quality synthesis of evidence for policy and practice has been missing. In this paper, we describe a new Cochrane review of interventions to prevent the occurrence or reoccurrence of elder abuse. Overall, the quality of the evidence available for decision making is very low and there is little to guide practice. Amongst the interventions, there is some evidence that teaching coping skills to family carers of persons with dementia might make the situation better. We argue that poor quality and wasteful research needs to be avoided, and front-line agencies be supported in undertaking comparative evaluation of their services.