In March of 2020, the province of Ontario declared a State of Emergency (SOE) to reduce the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus ...disease (COVID-19). This disruption to the economy provided an opportunity to measure change in air pollution when the population spends more time at home with fewer trips. Hourly air pollution observations were obtained for fine particulate matter, nitrogen dioxide, nitrogen oxides and ozone from the Ontario air monitoring network for 2020 and the previous five years. The analysis is focused on a five-week period during the SOE with a previous five-week period used as a control. Fine particulate matter did not show any significant reductions during the SOE. Ozone concentrations at 12 of the 32 monitors were lower than any of the previous five-years; however, four locations were above average. Average ozone concentrations were 1 ppb lower during the SOE, but this ranged at individual monitors from 1.5 ppb above to 4.2 ppb below long-term conditions. Nitrogen dioxide and nitrogen oxides demonstrated a reduction across Ontario, and both pollutants displayed their lowest concentrations for 22 of 29 monitors. Individual monitors ranged from 1 ppb (nitrogen dioxide) and 5 ppb (nitrogen oxides) above average to 4.5 (nitrogen dioxide) and 7.1 ppb (nitrogen oxides) below average. Overall, both nitrogen dioxide and nitrogen oxides demonstrated a reduction across Ontario in response to the COVID-19 SOE, ozone concentrations suggested a possible reduction, and fine particulate matter has not varied from historic concentrations.
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•Air pollution response to a region-wide state of emergency was assessed.•Fine particulate matter concentrations did not change.•Moderate evidence of ozone concentration reductions•Strong evidence for reductions of nitrogen dioxide and nitrogen oxides•Pollutants with transportation dominated source profiles responded the most.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
L’amélioration des schémas thérapeutiques des neuropathies périphériques nécessite la réalisation d’essais cliniques multicentriques. Pour les polyradiculonévrites inflammatoires démyélinisantes ...chroniques (PIDC), une étude contrôlée randomisée multicentrique a comparé les IgIV aux bolus de methylprednisolone (MP) pendant 6mois. Le critère de jugement principal était l’arrêt du traitement par inefficacité ou intolérance ; 45 patients ont été inclus. Plus de patients ont interrompu le MP que l’IgIV, le plus souvent par manque d’efficacité. Une étude multicentrique randomisée contrôlée (PREDICT) a évalué la rémission à long terme des PIDC après corticothérapie de courte durée (bolus de dexamethasone ou prednisolone) ; 39 patients ont été inclus : 26 % ont été guéris ou en rémission ; une rechute est survenue dans 50 % dans un délai de 11 à 17mois. Un diagnostic différentiel a été identifié chez 58 % des patients n’ayant répondu à aucun des traitements. Pour les PIDC réfractaires, une étude rétrospective a constaté la possibilité d’amélioration fonctionnelle dans 1 quart des cas après l’adjonction d’un agent immunomodulateur, la cyclosporine était associée au taux le plus élevé d’effets indésirables. Pour les neuropathies du syndrome de POEMS : l’évaluation à long terme de l’autogreffe de cellules souches hématopoïétiques dans le syndrome de POEMS montre la rareté de la rechute clinique (1/59), la possibilité de rechute biologique ou radiologique dans un quart des cas. Pour les neuropathies amyloïdes héréditaires : une étude multicentrique contre placebo a évalué le tafamidis (stabilisateur kinétique de la transthyrétine TTR) aux posologies de 20mg/j pendant 18mois dans les formes débutantes avec mutation Met30TTR ; elle a montré l’efficacité dans le groupe évaluable et a permis d’obtenir une AMM au stade 1 pour ralentir la progression de la neuropathie. Un algorithme décisionnel dans la prise en charge des neuropathies amyloïdes familiales a été proposé par le centre de référence des neuropathies amyloïdes familiales.
Improvement of therapeutic strategies for peripheral neuropathies requires multicentric clinical trials. For chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a randomized controlled multicentric study compared IgIV to pulses of methylprednisolone (MP) given for 6months. The primary endpoint was treatment discontinuation due to inefficacy or intolerance; 45 patients were enrolled: more patients had interrupted MP than IVIg, usually because of inefficacy. A multicentric randomized clinical trial (PREDICT) evaluated long-term remission of CIDP after short-term corticosteroid therapy (pulses of dexamethasone or prednisolone); 39 patients were enrolled: 26% achieved cure or remission, a relapse occurred in 50% after a delay of 11 to 17months. Differential diagnosis was identified in 58% of patients who had not responded to any therapy. For refractory CIDP, a retrospective study showed the possibility of functional improvement in 24% of cases after adjunction of animmunomodulatory agent; cyclosporine was associated with the highest rate of adverse events or side effects. In familial amyloidotic polyneuropathy, a multicentric controlled study against placebo with tafamidis, an akinetic stabilizer of transthyretin (TTR) 20mg/d, in early stage of Val30MetTTR showed efficiency in the evaluable group and led to marketing authorization by the EMA in stage 1 to slow the progression of the neuropathy. A Cochrane database system review showed that there are no randomized or quasi-randomized controlled clinical trials of treatment for POEMS syndrome, for neuropathies with anti-MAG antibodies, or multifocal motor neuropathy on which to base practice. This review underlines the usefulness of multicentric randomized trials to assess treatments in peripheral neuropathies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Reactive multilayer thin films are a class of energetic materials that continue to attract attention for use in joining applications and as igniters. Generally composed of two reactants, these ...heterogeneous solids can be stimulated by an external source to promptly release stored chemical energy in a sudden emission of light and heat. In this critical review article, results from recent investigations of these materials are discussed. Discussion begins with a brief description of the vapor deposition techniques that provide accurate control of layer thickness and film composition. More than 50 reactive film compositions have been reported to date, with most multilayers fabricated by magnetron sputter deposition or electron-beam evaporation. In subsequent sections, we review how multilayer ignition threshold, reaction rate, and total heat are tailored via thin film design. For example, planar multilayers with nanometer-scale periodicity exhibit rapid, self-sustained reactions with wavefront velocities up to 100m/s. Numeric and analytical models have elucidated many of the fundamental processes that underlie propagating exothermic reactions while demonstrating how reaction rates vary with multilayer design. Recent, time-resolved diffraction and imaging studies have further revealed the phase transformations and the wavefront dynamics associated with propagating chemical reactions. Many reactive multilayers (e.g., Co/Al) form product phases that are consistent with published equilibrium phase diagrams, yet a few systems, such as Pt/Al, develop metastable products. The final section highlights current and emerging applications of reactive multilayers. Examples include reactive Ni(V)/Al and Pd/Al multilayers which have been developed for localized soldering of heat-sensitive components.
•Vapor-deposited, reactive multilayers and their properties are reviewed.•This article includes discussion of various structure-property relationships.•Multilayers can be ignited at a point or by uniform heating.•Reactive multilayers can exhibit self-sustained, rapid deflagration reactions•This review summarizes current and emerging applications of reactive multilayers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cellular senescence is a proliferation arrest that is typically irreversible and caused by various cellular stresses, including excess rounds of cell division and cancer-causing genetic alterations. ...Senescence actively contributes to a tissue-level response to tissue wounding and incipient cancer, healing the tissue and suppressing tumor formation. However, in the long term, the same senescence program may hurt the tissue, thereby contributing to tissue aging. Tumor suppression, wound healing, and aging are each associated with inflammation, and here it is proposed that cellular senescence contributes to a “nonimmune cell” component of the tissue inflammatory response.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Malignant neoplasms are consistently among the top four leading causes of death in all age groups in the United States, despite a concerted effort toward developing novel therapeutic approaches 1. ...Our understanding of and therapeutic strategy for treating each of these neoplastic diseases have been improved through decades of research on the genetics, signaling pathways, and cellular biology that govern tumor cell initiation, progression and maintenance. Much of this work has concentrated on post-translational modifications and abnormalities at the DNA level, including point mutations, amplifications/deletions, and chromosomal translocations, and how these aberrant events affect the expression and function of protein-coding genes. Only recently has a novel class of conserved gene regulatory molecules been identified as a major contributor to malignant neoplastic disease. This review focuses on how these small non-coding RNA molecules, termed microRNAs (miRNAs), can function as oncogenes or tumor suppressors, and how the misexpression of miRNAs and dysregulation of factors that regulate miRNAs contribute to the tumorigenic process. Specific focus is given to more recently discovered regulatory mechanisms that go awry in cancer, and how these changes alter miRNA expression, processing, and function.
Adams et al. discuss how miRNAs can function as oncogenes or tumor suppressors, and how the misexpression of miRNAs and dysregulation of factors that regulate miRNAs contribute to the tumorigenic process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The analysis of phenotypic change is important for several evolutionary biology disciplines, including phenotypic plasticity, evolutionary developmental biology, morphological evolution, ...physiological evolution, evolutionary ecology and behavioral evolution. It is common for researchers in these disciplines to work with multivariate phenotypic data. When phenotypic variables exceed the number of research subjects--data called 'high-dimensional data'--researchers are confronted with analytical challenges. Parametric tests that require high observation to variable ratios present a paradox for researchers, as eliminating variables potentially reduces effect sizes for comparative analyses, yet test statistics require more observations than variables. This problem is exacerbated with data that describe 'multidimensional' phenotypes, whereby a description of phenotype requires high-dimensional data. For example, landmark-based geometric morphometric data use the Cartesian coordinates of (potentially) many anatomical landmarks to describe organismal shape. Collectively such shape variables describe organism shape, although the analysis of each variable, independently, offers little benefit for addressing biological questions. Here we present a nonparametric method of evaluating effect size that is not constrained by the number of phenotypic variables, and motivate its use with example analyses of phenotypic change using geometric morphometric data. Our examples contrast different characterizations of body shape for a desert fish species, associated with measuring and comparing sexual dimorphism between two populations. We demonstrate that using more phenotypic variables can increase effect sizes, and allow for stronger inferences.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Crosstalk between cellular metabolism and the epigenome regulates epigenetic and metabolic homeostasis and normal cell behavior. Changes in cancer cell metabolism can directly impact epigenetic ...regulation and promote transformation. Here we analyzed the contribution of methionine and serine metabolism to methylation of DNA and RNA. Serine can contribute to this pathway by providing one-carbon units to regenerate methionine from homocysteine. While we observed this contribution under methionine-depleted conditions, unexpectedly, we found that serine supported the methionine cycle in the presence and absence of methionine through de novo ATP synthesis. Serine starvation increased the methionine/S-adenosyl methionine ratio, decreasing the transfer of methyl groups to DNA and RNA. While serine starvation dramatically decreased ATP levels, this was accompanied by lower AMP and did not activate AMPK. This work highlights the difference between ATP turnover and new ATP synthesis and defines a vital function of nucleotide synthesis beyond making nucleic acids.
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•Serine supports the methionine cycle through de novo ATP synthesis•De novo ATP-synthesis is an important source of ATP in cancer cells•Methionine fed colorectal cancer cells do not detectably re-methylate homocysteine•A method to track methyl units from amino acids onto DNA and RNA is described
The methionine cycle generates S-adenosyl methionine (SAM), the primary cellular methyl donor. Serine may provide one-carbon units to regenerate methionine from homocysteine. Maddocks et al. show that in colorectal cancer cells serine also maintains the methionine cycle through de novo ATP synthesis, which supports the conversion of methionine to SAM.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We are facing accelerated global warming due to the accumulation of greenhouse gases. A hydrogen-based economy is one potential approach toward maintaining our standard of living while lowering ...carbon dioxide emissions. Palladium is a unique material with a strong affinity to hydrogen owing to both its catalytic and hydrogen absorbing properties. Palladium has the potential to play a major role in virtually every aspect of the envisioned hydrogen economy, including hydrogen purification, storage, detection, and fuel cells. Major aspects of current research and potential applications of palladium-based nanomaterials in various hydrogen technologies are presented in this review.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Age-associated changes to the mammalian DNA methylome are well documented and thought to promote diseases of aging, such as cancer. Recent studies have identified collections of individual ...methylation sites whose aggregate methylation status measures chronological age, referred to as the DNA methylation clock. DNA methylation may also have value as a biomarker of healthy versus unhealthy aging and disease risk; in other words, a biological clock. Here we consider the relationship between the chronological and biological clocks, their underlying mechanisms, potential consequences, and their utility as biomarkers and as targets for intervention to promote healthy aging and longevity.
Analysis of age-associated methylation changes at CpG sites has allowed the construction of DNA methylation clocks. Field et al. discuss the potential causes and consequences of these clocks. Comparisons between biological and chronological methylation clocks suggest routes toward their effective application in the treatment and prevention of age-associated disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP