Weak instruments arise when the instruments in linear instrumental variables (IV) regression are weakly correlated with the included endogenous variables. In generalized method of moments (GMM), more generally, weak instruments correspond to weak identification of some or all of the unknown parameters. Weak identification leads to GMM statistics with nonnormal distributions, even in large samples, so that conventional IV or GMM inferences are misleading. Fortunately, various procedures are now available for detecting and handling weak instruments in the linear IV model and, to a lesser degree, in nonlinear GMM.

A Survey of Weak Instruments and Weak Identification in Generalized Method of Moments

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This article offers a framework to understand how endogeneity arises and how to control for it with instrumental variables to estimate causal relations with observational data. It builds on the state-of-the-art research in applied and theoretical econometrics to highlight the importance of endogeneity and review the methods that can be used to address it with instrumental variables.The article also discusses when the Heckman two-step procedure can be used, as well as the tests, methods and assumptions that researchers should check when using instrumental variables.To ease implementation of the instrumental variables techniques, the author offers the STATA commands of the exposed tests and methods. Further, an empirical example is provided along with the utilized STATA codes. In the end, this article serves as a`toolkit' allowing scholars not only to understand whether endogeneity is present in their empirical setting, but also to assess the empirical validity of their work when using instrumental variables.

https://journals.sagepub.com/doi/pdf/10.1177/1476127008094339

Controlling for endogeneity with instrumental variables in strategic management research

Nitroaromatic compounds are released into the biosphere almost exclusively from anthropogenic sources. Some compounds are produced by incomplete combustion of fossil fuels; others are used as synthetic intermediates, dyes, pesticides, and explosives. Recent research revealed a number of microbial systems capable of transforming or biodegrading nitroaromatic compounds. Anaerobic bacteria can reduce the nitro group via nitroso and hydroxylamino intermediates to the corresponding amines. Isolates of Desulfovibrio spp. can use nitroaromatic compounds as their source of nitrogen. They can also reduce 2,4,6-trinitrotoluene to 2,4,6-triaminotoluene. Several strains of Clostridium can catalyze a similar reduction and also seem to be able to degrade the molecule to small aliphatic acids. Anaerobic systems have been demonstrated to destroy munitions and pesticides in soil. Fungi can extensively degrade or mineralize a variety of nitroaromatic compounds. For example, Phanerochaete chrysosporium mineralizes 2,4-dinitrotoluene and 2,4,6-trinitrotoluene and shows promise as the basis for bioremediation strategies. The anaerobic bacteria and the fungi mentioned above mostly transform nitroaromatic compounds via fortuitous reactions. In contrast, a number of nitroaromatic compounds can serve as growth substrates for aerobic bacteria. Removal or productive metabolism of nitro groups can be accomplished by four different strategies. (a) Some bacteria can reduce the aromatic ring of dinitro and trinitro compounds by the addition of a hydride ion to form a hydride-Meisenheimer complex, which subsequently rearomatizes with the elimination of nitrite. (b) Monooxygenase enzymes can add a single oxygen atom and eliminate the nitro group from nitrophenols. (c) Dioxygenase enzymes can insert two hydroxyl groups into the aromatic ring and precipitate the spontaneous elimination of the nitro group from a variety of nitroaromatic compounds. (d) Reduction of the nitro group to the corresponding hydroxylamine is the initial reaction in the productive metabolism of nitrobenzene, 4-nitrotoluene, and 4-nitrobenzoate. The hydroxylamines undergo enzyme-catalyzed rearrangements to hydroxylated compounds that are substrates for ring-fission reactions. Potential applications of the above reactions include not only the biodegradation of environmental contaminants, but also biocatalysis and synthesis of valuable organic molecules.

Biodegradation of Nitroaromatic Compounds

The overuse or misuse of antibiotics has accelerated antibiotic resistance, creating a major challenge for the public health in the world. Sewage treatment plants (STPs) are considered as important reservoirs for antibiotic resistance genes (ARGs) and activated sludge characterized with high microbial density and diversity facilitates ARG horizontal gene transfer (HGT) via mobile genetic elements (MGEs). However, little is known regarding the pool of ARGs and MGEs in sludge microbiome. In this study, the transposon aided capture (TRACA) system was employed to isolate novel plasmids from activated sludge of one STP in Hong Kong, China. We also used Illumina Hiseq 2000 high-throughput sequencing and metagenomics analysis to investigate the plasmid metagenome. Two novel plasmids were acquired from the sludge microbiome by using TRACA system and one novel plasmid was identified through metagenomics analysis. Our results revealed high levels of various ARGs as well as MGEs for HGT, including integrons, transposons and plasmids. The application of the TRACA system to isolate novel plasmids from the environmental metagenome, coupled with subsequent high-throughput sequencing and metagenomic analysis, highlighted the prevalence of ARGs and MGEs in microbial community of STPs.

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Plasmid Metagenome Reveals High Levels of Antibiotic Resistance Genes and Mobile Genetic Elements in Activated Sludge

Microorganisms that can utilize halogenated compounds as a growth substrate generally produce enzymes whose function is carbon-halogen bond cleavage. Based on substrate range, reaction type and gene sequences, the dehalogenating enzymes can be classified in different groups, including hydrolytic dehalogenases, glutathione transferases, monooxygenases and hydratases. X-ray crystallographic and biochemical studies have provided detailed mechanistic insight into the action of haloalkane dehalogenase. The essential features are nucleophilic substitution of the halogen by a carboxylate group and the presence of a distinct halogen binding site, formed by tryptophan residues. This review summaries current knowledge on a variety of other dehalogenating enzymes and indicates the existence of a widespread and diverse microbial potential for dechlorination of natural and xenobiotic halogenated compounds.

Genetics and biochemistry of dehalogenating enzymes

Monobromoacetate (MBA) is toxic for the 1,2-dichloroethane-degrading bacterium Xanthobacter autotrophicus GJ10 at concentrations higher than 5 mM. Mutants which are able to grow on higher concentrations of MBA were isolated and found to overexpress haloacid dehalogenase, which is encoded by the dhlB gene. In mutant GJ10M50, a DNA fragment (designated IS1247) had copied itself from a position on the chromosome that was not linked to the dhlB region to a site immediately upstream of dhlB, resulting in a 1,672-bp insertion. IS1247 was found to encode an open reading frame corresponding to 464 amino acids which showed similarity to putative transposases from two other insertion elements. In most of the other MBA-resistant mutants of GJ10, IS1247 was also present in one more copy than in the wild type, which had two copies located within 20 kb. After insertion to a site proximal to dhlB, IS1247 was able to transpose itself together with the dhlB gene to a plasmid, without the requirement of a second insertion element being present downstream of dhlB. The results show that IS1247 causes bromoacetate resistance by overexpression and mobilization of the haloacid dehalogenase gene, which mimics steps during the evolution of a catabolic transposon and plasmid during adaptation to a toxic growth substrate.

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Adaptation of Xanthobacter autotrophicus GJ10 to Bromoacetate due to Activation and Mobilization of the Haloacetate Dehalogenase Gene by Insertion Element IS1247

The paper considers the estimation of the coefficients of a single equation in the presence of dummy intruments We derive pseudo ML and GMM estimators based on moment restrictions induced either by the structural form or by the reduced form of the model The performance of the estimators is evaluated for the non-Gaussian case We allow for heteroscedasticity The asymptotic distributions are based on parameter sequences where the number of instruments increases at the same rate as the sample size Relaxing the usual Gaussian assumption is shown to affect the normal asymptotic distributions As a result also recently suggested new specification tests for the validity of instruments depend on Gaussianity Monte Carlo simulations confirm the accuracy of the asymptotic approach

/pdf/instrumental-variable-estimation-based-on-grouped-data-5d5q464d6y.pdf

Instrumental variable estimation based on grouped data

The paper considers the estimation of the coefficients of a single equation in the presence of dummy intruments. We derive pseudo ML and GMM estimators based on moment restrictions induced either by the structural form or by the reduced form of the model. The performance of the estimators is evaluated for the non-Gaussian case. We allow for heteroscedasticity. The asymptotic distributions are based on parameter sequences where the number of instruments increases at the same rate as the sample size. Relaxing the usual Gaussian assumption is shown to affect the normal asymptotic distributions. As a result also recently suggested new specification tests for the validity of instruments depend on Gaussianity. Monte Carlo simulations confirm the accuracy of the asymptotic approach.

Instrumental Variable Estimation Based on Grouped Data

Dichloroethane (1,2-DCE) is a synthetic compound that is not known to be formed naturally. Nevertheless, several pure microbial cultures are able to use it as a sole carbon source for growth. Degradation of 1,2-DCE proceeds via 2-chloroethanol, chloroacetaldehyde and chloroacetate to glycolate. The genes encoding the enzymes responsible for the conversion of 1,2-DCE to glycolic acid have been isolated. The haloalkane dehalogenase and an aldehyde dehydrogenase are plasmid encoded. Two other enzymes, the alcohol dehydrogenase and the haloacid dehalogenase, are chromosomally encoded. Sequence analysis indicates that the haloacid dehalogenase belongs to the L-specific 2-chloroproprionic acid dehalogenases. From the three-dimensional structure and sequence similarities, the haloalkane dehalogenase appears to be a member of the α/β hydrolase fold hydrolytic enzymes, of which several are involved in the degradation of aromatic and aliphatic xenobiotic compounds.

/pdf/genetics-and-biochemistry-of-1-2-dichloroethane-degradation-50ud5zfux5.pdf

Jan van der Ploeg

Papers

Genetics and biochemistry of dehalogenating enzymes

Adaptation of Xanthobacter autotrophicus GJ10 to Bromoacetate due to Activation and Mobilization of the Haloacetate Dehalogenase Gene by Insertion Element IS1247

Instrumental variable estimation based on grouped data

Instrumental Variable Estimation Based on Grouped Data

Genetics and biochemistry of 1,2-dichloroethane degradation