Simpson’s Paradox in the interpretation of “leaky pipeline” data

The traditional ‘leaky pipeline’ plots are widely used to inform gender equality policy and practice. Herein, we demonstrate how a statistical phenomenon known as Simpson’s paradox can obscure trends in gender ‘leaky pipeline’ plots. Our approach has been to use Excel spreadsheets to generate hypothetical ‘leaky pipeline’ plots of gender inequality within an organisation. The principal factors, which make up these hypothetical plots, can be input into the model so that a range of potential situations can be modelled. How the individual principal factors are then reflected in ‘leaky pipeline’ plots is shown. We find that the effect of Simpson’s paradox on leaky pipeline plots can be simply and clearly illustrated with the use of hypothetical modelling and our study augments the findings in other statistical reports of Simpson’s paradox in clinical trial data and in gender inequality data. The findings in this paper, however, are presented in a way, which makes the paradox accessible to a wide range of people

Bahasa, Citra, Media

Pers, radio, televisi, iklan, dan fotografi, masing-masing memiliki cara khas mengonstruksi dan menyampaikan pesan. “Bahasa” mereka, yang terbentuk dari ucapan dan teks tertulis, gambar diam dan bergerak, sama dalam satu hal: semuanya merupakan ekspresi dari dan kendaraan untuk menstrukturkan serta memperkuat hubungan sosial dan politik tertentu. Esai-esai dalam buku ini mengeksplorasi dan mengurai pelbagai cara halus bagaimana media bekerja melegitimasi status quo dan memanipulasi citraan agar sesuai dengan pandangan dominan. Howard Davis dan Paul Walton mencoba menyuguhkan riset yang menguji seberapa jauh berita televisi menyimpang dari keharusannya agar tidak berpihak. Dalam esai berjudul Kematian Seorang Perdana Menteri: Konsensus dan Penutupan dalam Berita Internasional (Bab 1), Davis dan Walton melakukan analisis sistematis terhadap peristiwa yang akan menarik pelbagai interpretasi yang bertentangan dan kemudian menyelidiki apakah ada beragam sudut pandang dalam berita itu. Dengan mengangkat kisah pembunuhan Aldo Moro, mereka menganalisis makrostruktur teks, membuat daftar istilah deskriptif yang berlaku bagi para protagonis serta membuat perbandingan bahasa dan gaya dari contoh-contoh liputan pers. Materi yang mereka gunakan adalah kosakata berita dari rekaman dan transkrip pelbagai lembaga penyiaran jaringan berita utama di Inggris, Jerman dan AS. Pada Bab 7, Walery Pisarek menghadirkan perbandingan bahasa representasi pers negara sosial dan negara kapitalis dalam esai Barat dan Timur “Realitas”. Dengan menggunakan kamus kekerapan kata sebagai material analisis, ia membandingkan frekuensi kata benda dan kata sifat. Salah satu simpulannya, surat kabar sosialis lebih mementingkan apa yang dianggap memiliki konsekuensi sosial dan ekonomi dibandingkan surat kabar kapitalis. Anda juga akan secara rutin melakukan identifikasi, memahami dan mengkritik iklan ketika menonton televisi, mendengarkan radio, atau melewati papan reklame selepas membaca esai Bagaimana Memahami Iklan Menjadi Hal yang Dimungkinkan (Bab 9) yang dibesut Trevor Pateman. Merujuk pernyataan Barthes bahwa keadaan kontras antara makna denotatif dan konotatif memainkan peran sentral dalam strukturalisme dan semiologi, Pateman memberi argumen: makna denotatif operatif suatu periklanan tidak bisa dirinci tanpa merujuk pada variabel kontekstual (atau pragmatis) (hlm. 211). Semua esai dalam buku ini menarik wawasan dari sejumlah disiplin yang telah mapan maupun yang baru muncul, termasuk sosiolinguistik, analisis wacana, pragmatika, semiotika, dan sosiologi komunikasi. Setelah disatukan, semua esai ini merepresentasikan contoh karya kontemporer terbaik dan paling menarik mengenai topik bahasa, pencitraan, dan kajian media. Analisisnya terikat kuat dengan ilustrasi yang antara lain mencakup bahasa radio, gambar diam dari televisi, kartun, iklan, dan tata letak surat kabar

The Molecular Mechanisms of Oxygen Activation and Hydrogen Peroxide Formation in Lytic Polysaccharide Monooxygenases

Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes for the degradation of recalcitrant polysaccharides such as chitin and cellulose. Unlike classical hydrolytic enzymes (cellulases), LPMOs catalyze the cleavage of the glycosidic bond via an oxidative mechanism using oxygen and a reductant. The full enzymatic molecular mechanisms, starting from the initial electron transfer from a reductant to oxygen activation and hydrogen peroxide formation, are not yet understood. Using QM/MM metadynamics simulations, we have uncovered the oxygen activation mechanisms by LPMO in the presence of ascorbic acid, one of the most-used reductants in LPMOs assays. Our simulations capture the sequential formation of Cu(II)-O2- and Cu(II)-OOH- intermediates via facile H-atom abstraction from ascorbate. By investigating all the possible reaction pathways from the Cu(II)−OOH- intermediate, we ruled out Cu(II)-O•- formation via direct O-O cleavage of Cu(II)-OOH-. Meanwhile, we identified a possible pathway in which the proximal oxygen atom of Cu(II)−OOH- abstracts a hydrogen atom from ascorbate, leading to Cu(I) and H2O2. The “in situ” generated H2O2 either converts to LPMO-Cu(II)-O•- via a homolytic reaction, or diffuses into the bulk water in an uncoupled pathway. The competition of these two pathways is strongly dependent on the binding of the carbohydrate substrate, which plays a role in barricading the “in situ” generated H2O2 molecule, preventing its diffusion from the active site into the bulk water. Based on the present results, we propose a catalytic cycle of LPMOs that is consistent with the experimental information available. In particular, it explains the enigmatic substrate-dependence of the reactivity of the LPMO with H2O2

Insights from semi-oriented EPR spectroscopy studies into the interaction of lytic polysaccharide monooxygenases with cellulose

Probing the detailed interaction between lytic polysaccharide monooxygenases (LPMOs) and their polysaccharide substrates is key to revealing further insights into the mechanism of action of this class of enzymes on recalcitrant biomass. This investigation is somewhat hindered, however, by the insoluble nature of the substrates, which precludes the use of most optical spectroscopic techniques. Herein, we report a new semi-oriented EPR method which evaluates directly the binding of cellulose-active LPMOs to crystalline cellulose. We make use of the intrinsic order of cellulose fibres in Apium graveolens (celery) to orient the LPMO with respect to the magnetic field of an EPR spectrometer. The subsequent angle-dependent changes observed in the EPR spectra can then be related to the orientation of the g matrix principal directions with respect to the magnetic field of the spectrometer and, hence, to the binding of the enzyme onto the cellulose fibres. This method, which does not require specific modification of standard CW-EPR equipment, can be used as a general procedure to investigate LPMO–cellulose interactions

Formation of a copper(II)-tyrosyl complex at the active site of lytic polysaccharide monooxygenases following oxidation by H2O2

Hydrogen peroxide is a cosubstrate for the oxidative cleavage of saccharidic substrates by copper-containing lytic polysaccharide monooxygenases (LPMOs). The rate of reaction of LPMOs with hydrogen peroxide is high, but it is accompanied by rapid inactivation of the enzymes, presumably through protein oxidation. Herein, we use UV− vis, CD, XAS, EPR, VT/VH-MCD, and resonance Raman spectroscopies, augmented with mass spectrometry and DFT calculations, to show that the product of reaction of an AA9 LPMO with H2O2 at higher pHs is a singlet Cu(II)−tyrosyl radical species, which is inactive for the oxidation of saccharidic substrates. The Cu(II)−tyrosyl radical center entails the formation of significant Cu(II)−(●OTyr) overlap, which in turn requires that the plane of the d(x2−y2) SOMO of the Cu(II) is orientated toward the tyrosyl radical. We propose from the Marcus cross-relation that the active site tyrosine is part of a “hole-hopping” charge-transfer mechanism formed of a pathway of conserved tyrosine and tryptophan residues, which can protect the protein active site from inactivation during uncoupled turnover

Discovery of a fungal copper radical oxidase with high catalytic efficiency towards 5-hydroxymethylfurfural and benzyl alcohols for green bioprocessing

Copyright © 2020 American Chemical Society. Alternatives to petroleum-based chemicals are highly sought-after for ongoing efforts to reduce the damaging effects of human activity on the environment. Copper radical oxidases from Auxiliary Activity Family 5/Subfamily 2 (AA5_2) are attractive biocatalysts because they oxidize primary alcohols in a chemoselective manner without complex organic cofactors. However, despite numerous studies on canonical galactose oxidases (GalOx, EC 1.1.3.9) and engineered variants, and the recent discovery of a Colletotrichum graminicola copper radical alcohol oxidase (AlcOx, EC 1.1.3.13), the catalytic potentials of very few AA5_2 members have been characterized. Guided by the sequence similarity network and phylogenetic analyses, we targeted a distinct paralog from the fungus C. graminicola as a representative member of a large uncharacterized subgroup of AA5_2. Through recombinant production and detailed kinetic analysis, we demonstrated that this enzyme is weakly active toward carbohydrates but efficiently catalyzes the oxidation of aryl alcohols to the corresponding aldehydes. As such, this represents the initial characterization of a demonstrable aryl alcohol oxidase (AAO, EC 1.1.3.7) in AA5, an activity which is classically associated with flavin-dependent glucose-methanol-choline (GMC) oxidoreductases of Auxiliary Activity Family 3 (AA3). X-ray crystallography revealed a distinct multidomain architecture comprising an N-terminal PAN domain abutting a canonical AA5 seven-bladed propeller catalytic domain. Of direct relevance to biomass processing, the wild-type enzyme exhibits the highest activity on the primary alcohol of 5-hydroxymethylfurfural (HMF), a product of significant interest in the lignocellulosic biorefinery concept. Thus, the chemoselective oxidation of HMF to 2,5-diformylfuran (DFF) by C. graminicola aryl alcohol oxidase (CgrAAO) from AA5 provides a fundamental building block for chemistry via biotechnology

A fungal family of lytic polysaccharide monooxygenase-like copper proteins

Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes that play a key role in the oxidative degradation of various biopolymers such as cellulose and chitin. While hunting for new LPMOs, we identified a new family of proteins, defined here as X325, in various fungal lineages. The three-dimensional structure of X325 revealed an overall LPMO fold and a His brace with an additional Asp ligand to Cu(II). Although LPMO-type activity of X325 members was initially expected, we demonstrated that X325 members do not perform oxidative cleavage of polysaccharides, establishing that X325s are not LPMOs. Investigations of the biological role of X325 in the ectomycorrhizal fungus Laccaria bicolor revealed exposure of the X325 protein at the interface between fungal hyphae and tree rootlet cells. Our results provide insights into a family of copper-containing proteins, which is widespread in the fungal kingdom and is evolutionarily related to LPMOs, but has diverged to biological functions other than polysaccharide degradation

In Search of Cellular Immunophenotypes in the Blood of Children with Autism

Autism is a neurodevelopmental disorder characterized by impairments in social behavior, communication difficulties and the occurrence of repetitive or stereotyped behaviors. There has been substantial evidence for dysregulation of the immune system in autism.We evaluated differences in the number and phenotype of circulating blood cells in young children with autism (n = 70) compared with age-matched controls (n = 35). Children with a confirmed diagnosis of autism (4-6 years of age) were further subdivided into low (IQ<68, n = 35) or high functioning (IQ ≥ 68, n = 35) groups. Age- and gender-matched typically developing children constituted the control group. Six hundred and forty four primary and secondary variables, including cell counts and the abundance of cell surface antigens, were assessed using microvolume laser scanning cytometry.There were multiple differences in immune cell populations between the autism and control groups. The absolute number of B cells per volume of blood was over 20% higher for children with autism and the absolute number of NK cells was about 40% higher. Neither of these variables showed significant difference between the low and high functioning autism groups. While the absolute number of T cells was not different across groups, a number of cellular activation markers, including HLA-DR and CD26 on T cells, and CD38 on B cells, were significantly higher in the autism group compared to controls.These results support previous findings that immune dysfunction may occur in some children with autism. Further evaluation of the nature of the dysfunction and how it may play a role in the etiology of autism or in facets of autism neuropathology and/or behavior are needed

The role of hydrogen and fuel cells in the global energy system

Hydrogen technologies have experienced cycles of excessive expectations followed by disillusion. Nonetheless, a growing body of evidence suggests these technologies form an attractive option for the deep decarb onisation of global energy systems, and that recent improvements in their cost and performance point towards economic viability as well. This paper is a comprehensive review of the potential role that hydrogen could play in the provision of electricity, h eat, industry, transport and energy storage in a low - carbon energy system, and an assessment of the status of hydrogen in being able to fulfil that potential. The picture that emerges is one of qualified promise: hydrogen is well established in certain nic hes such as forklift trucks, while mainstream applications are now forthcoming. Hydrogen vehicles are available commercially in several countries, and 225,000 fuel cell home heating systems have been sold. This represents a step change from the situation of only five years ago. This review shows that challenges around cost and performance remain, and considerable improvements are still required for hydrogen to become truly competitive. But such competitiveness in the medium - term future no longer seems an unrealistic prospect, which fully justifies the growing interest and policy support for these technologies around the world