A power-efficient thermocycler based on induction heating for DNA amplification by polymerase chain reaction

We have built a thermocycler based on the principles of induction heating for polymerase chain reaction (PCR) of target sequences in DNA samples of interest. The cycler has an average heating rate of ~0.8°C/s and a cooling rate of ~0.5°C/s, and typically takes ~4 h to complete a 40-cycle PCR protocol. It is power-efficient (~6 W per reaction tube), micro-processor controlled, and can be adapted for battery operation. Using this instrument, we have successfully amplified a 350 bp segment from a plasmid and SRY, the human sex determining gene, which occurs as a single-copy sequence in genomic DNA of human males. The PCR products from this thermocycler are comparable to those obtained by the use of commercially available machines. Its easy front-end operation, low-power design, portability and low cost makes it suitable for diagnostic field applications of PCR

Inactivators of Isoniazid, Based on The Ratio of The Urinary Excretion of Acetylisoniazid To Isoniazid

Following an intramuscular injection of isoniazid 3 mg/kg body-weight, the urinary excretion of isoniazid and acetylisoniazid during the periods 0-1, 1-2, 2-3 and 3-4 h was determined for 124 patients with pulmonary tuberculosis. On the same occasion, the serum isoniazid concentration at 4½ h was determined by microbiologic assay. The ratios of acetylisoniazid to isoniazid in the urine collections at 2, 3 and 4 h. were bimodally distributed. Rules were derived from these. ratios for classifying subjects as slow or rapid inactivators of isoniazid. There was 100% agreement between the classification based on each of these ratios and that based on the serum isoniazid concentration at 4½ h

Global health burden of ambient PM2.5 and the contribution of anthropogenic black carbon and organic aerosols

Chronic exposure to fine particulate matter (PM2.5) poses a major global health risk, commonly assessed by assuming equivalent toxicity for different PM2.5 constituents. We used a data-informed global atmospheric model and recent exposure-response functions to calculate the health burden of ambient PM2.5 from ten source categories. We estimate 4.23 (95% confidence interval 3.0-6.14) million excess deaths annually from the exposure to ambient PM2.5. We distinguished contributions and major sources of black carbon (BC), primary organic aerosols (POA) and anthropogenic secondary organic aerosols (aSOA). These components make up to similar to 20% of the total PM2.5 in South and East Asia and East Africa. We find that domestic energy use by the burning of solid biofuels is the largest contributor to ambient BC, POA and aSOA globally. Epidemiological and toxicological studies indicate that these compounds may be relatively more hazardous than other PM2.5 compounds such as soluble salts, related to their high potential to inflict oxidative stress. We performed sensitivity analyses by considering these species to be more harmful compared to other compounds in PM2.5, as suggested by their oxidative potential using a range of potential relative risks. These analyses show that domestic energy use emerges as the leading cause of excess mortality attributable to ambient PM2.5, notably in Asia and Africa. We acknowledge the uncertainties inherent in our assumed enhanced toxicity of the anthropogenic organic and BC aerosol components, which suggest the need to better understand the mechanisms and magnitude of the associated health risks and the consequences for regulatory policies. However our assessment of the importance of emissions from domestic energy use as a cause of premature mortality is robust to a range of assumptions about the magnitude of the excess risk.Peer reviewe

Lepidorbitoides (Foraminifera) from the lower Maastrichtian Kallankuruchchi Formation, Cauvery Basin, India: Morphometry and paleobiogeography

The southernmost occurrence of the early Maastrichtian larger benthic foraminifera (LBF) in Tethys is known from the Kallankuruchchi Formation in the Cauvery Basin, SE India, represented by Lepidorbitoides-Siderolites assemblages. The systematics, age and paleobiogeography of Lepidorbitoides here have as yet remained unresolved due to lack of information particularly on the nepionic arrangement, whereas their links with the Western Tethyan and Caribbean biogeographic domains were speculated. Lepidorbitoides, studied from the same level in seven samples in two separate areas, invariably possess quadriserial nepionts and adauxiliary chamberlets, whose mean number ranges from 3.79 to 4.67. The ratio between the sample means of the internal diameter of deuteroconch and protoconch varies between 1.72 and 1.86. The equatorial layer in the early stage consists of arcuate chambers with basal stolons, and ogival-to spatulate chamberlets with annular and oblique stolons in the later stages. These features are consistent with the phylogenetically advanced members of the Western Tethyan Lepidorbitoides lineage, such as L. minor (Schlumberger) and L. socialis (Leymerie), and all samples were assigned to the transitional development stages of these species based on the morphometry. The taxonomic status of some Lepidorbitoides species, originally described from the Kallankuruchchi Formation and widely adopted in previous works, such as L. blanfordi (Rao) and L. inornata (Rao), are not justified. We extend the geographic range of Western Tethyan Lepidorbitoides to southern India. © 2017 Elsevier Lt

Global and national assessment of the incidence of asthma in children and adolescents from major sources of ambient NO₂

Abstract Pediatric asthma incidence has been associated with exposure to nitrogen dioxide (NO2) in ambient air. NO2 is predominantly emitted through fossil fuel use in land transportation, power generation and the burning of solid biofuels in households. We simulated NO2 with a global atmospheric chemistry model, combined with a land use regression model, to estimate NO2 exposure in all countries worldwide. The global asthma incidence among children and adolescents attributable to NO2 was estimated by deriving an exposure-response function from a meta-analysis which included epidemiological studies from multiple countries, baseline incidence rates from the Global Burden of Disease and gridded population data. The sectoral contribution to pediatric asthma from NO2 exposure (NO2-related asthma incidence: NINC) was estimated for different source categories to provide guidance to mitigation policies. We estimate 3.52 (2.1�6.0) million NINC per year globally, being about 14% of the total asthma incidence cases among children and adolescents. We find that emissions from land transportation are the leading contributor to NINC globally (?44%), followed by the domestic burning of solid fuels (?10.3%) and power generation from fossil fuels (?8.7%). Biogenic emissions which are not anthropogenically induced may contribute ?14% to the total NINC. Our results show large regional differences in source contributions, as the domestic burning of solid fuels is a main contributor to NINC in India and Nepal (?25%), while emissions from shipping are the leading source in Scandinavian countries (?40%), for example. While only 5% of all children and adolescents live in areas where NO2 exceeds the WHO annual guideline of 21.25 ppb (40 ?g m?3) for NO2, about 90% of the NINC is found in regions that meet the WHO guideline, related to the uneven distribution of children and adolescents in the population. This suggests the need for stricter policies to reduce NO2 exposure, and revisiting the current WHO guideline to reduce the health risks of children and adolescents.</jats:p

An exploratory study of international opportunity identification among family firms

This research examines how family firms identify international opportunities. Family firms are characterised by long-term orientation, being risk averse, and benefiting from familiness capital, resources and capabilities related to family involvement and interactions. Built upon opportunity identification theory and in two perspectives of accidental discovery and purposeful search, we explore the role of social and business networks, and prior knowledge in a first and subsequent international opportunity identification by family firms. In addition, we attempt to understand the role of family characteristics in the process of opportunity identification. Multiple case studies were carried out with seven family businesses from emerging economies, namely, India, Turkey and Taiwan. The findings of this research illustrate that because of being risk averse and long-term oriented, family firms are more likely to identify the first international opportunity through accidental discovery and subsequent international opportunities through purposeful search. The findings of this research show that, as risk-averse firms, family firms are not proactive in initiating international opportunity identification but rather learn about opportunities through accidental discovery. After the first experience of internationalisation, family firms engage in a more purposeful search to identify avenues that will aid their longevity through internationalisation. In the identification of firms' first international opportunities, it is mainly social networks that play a crucial role, especially those that contain international industry and market-specific knowledge. There is also a positive relationship between a family entrepreneur's prior knowledge and international opportunity identification and this relationship is moderated by the prior knowledge of their network. Familiness capital of these organisations can also play a role in long-term international opportunity identification

Combinatorial Polymer Electrospun Matrices Promote Physiologically-Relevant Cardiomyogenic Stem Cell Differentiation

Myocardial infarction results in extensive cardiomyocyte death which can lead to fatal arrhythmias or congestive heart failure. Delivery of stem cells to repopulate damaged cardiac tissue may be an attractive and innovative solution for repairing the damaged heart. Instructive polymer scaffolds with a wide range of properties have been used extensively to direct the differentiation of stem cells. In this study, we have optimized the chemical and mechanical properties of an electrospun polymer mesh for directed differentiation of embryonic stem cells (ESCs) towards a cardiomyogenic lineage. A combinatorial polymer library was prepared by copolymerizing three distinct subunits at varying molar ratios to tune the physicochemical properties of the resulting polymer: hydrophilic polyethylene glycol (PEG), hydrophobic poly(ε-caprolactone) (PCL), and negatively-charged, carboxylated PCL (CPCL). Murine ESCs were cultured on electrospun polymeric scaffolds and their differentiation to cardiomyocytes was assessed through measurements of viability, intracellular reactive oxygen species (ROS), α-myosin heavy chain expression (α-MHC), and intracellular Ca2+ signaling dynamics. Interestingly, ESCs on the most compliant substrate, 4%PEG-86%PCL-10%CPCL, exhibited the highest α-MHC expression as well as the most mature Ca2+ signaling dynamics. To investigate the role of scaffold modulus in ESC differentiation, the scaffold fiber density was reduced by altering the electrospinning parameters. The reduced modulus was found to enhance α-MHC gene expression, and promote maturation of myocyte Ca2+ handling. These data indicate that ESC-derived cardiomyocyte differentiation and maturation can be promoted by tuning the mechanical and chemical properties of polymer scaffold via copolymerization and electrospinning techniques

Toxicity assessment of organic contaminants: evaluation of mixture effects in model industrial mixtures using 2n full factorial design

Toxic organic chemicals present in industrial effluents were screened to design mixtures for examining the significant main and interaction effects among mixture components. A set of five four-component mixtures was selected by examining effluents from organic chemical, textile-dye, pulp-paper and petroleum refinery industries. The screening was based on their discharge, solubility, toxicity and volatility. A 2n full factorial approach was used in designing the mixtures, containing components at two dose levels, EC10(−) and EC40(+). Each mixture resulted in 16 combinations. Mixture toxicity was measured using the Vibrio fischeri bioluminescence inhibition assay. The main effects and binary, ternary and quaternary interaction effects were determined and the significance of effects was evaluated using normal order score and multifactor ANOVA. The organic chemicals retained after screening included, acetaldehyde, aniline, n-butanol, p-cresol, catechol, ethylbenzene, naphthalene, phenol, 1,2,4 trimethylbenzene and o-xylene. In all mixtures, the magnitude of main effects was more significant than the interaction effects. The trend in the main effect of components in any mixture was affected by the trends in the physico-chemical properties of the components, i.e., partition coefficient, molecular size and polarity. In some mixtures, a component with significantly higher concentration and significantly lower toxicity was found to depict a relatively high main effect, as observed for acetaldehyde in mixture I and n-butanol in mixture III. Normal order score approach failed to identify the significant interaction effects that could be identified using multifactor ANOVA. In general, the binary interactions were more significant than the ternary and quaternary interactions.© Elsevie

Nature and prevalence of non-additive toxic effects in industrially relevant mixtures of organic chemicals

The concentration addition (CA) and the independent action (IA) models are widely used for predicting mixture toxicity based on its composition and individual component dose–response profiles. However, the prediction based on these models may be inaccurate due to interaction among mixture components. In this work, the nature and prevalence of non-additive effects were explored for binary, ternary and quaternary mixtures composed of hydrophobic organic compounds (HOCs). The toxicity of each individual component and mixture was determined using the Vibrio fischeri bioluminescence inhibition assay. For each combination of chemicals specified by the 2n factorial design, the percent deviation of the predicted toxic effect from the measured value was used to characterize mixtures as synergistic (positive deviation) and antagonistic (negative deviation). An arbitrary classification scheme was proposed based on the magnitude of deviation (d) as: additive (⩽10%, class-I) and moderately (10 50%, class-IV) antagonistic/synergistic. Naphthalene, n-butanol, o-xylene, catechol and p-cresol led to synergism in mixtures while 1, 2, 4-trimethylbenzene and 1, 3-dimethylnaphthalene contributed to antagonism. Most of the mixtures depicted additive or antagonistic effect. Synergism was prominent in some of the mixtures, such as, pulp and paper, textile dyes, and a mixture composed of polynuclear aromatic hydrocarbons. The organic chemical industry mixture depicted the highest abundance of antagonism and least synergism. Mixture toxicity was found to depend on partition coefficient, molecular connectivity index and relative concentration of the components.© Elsevie