Reading for our time Miller, J. Hillis; Miller, J. Hillis
2012., 20120305, 2012, 2012-03-05
eBook
Can reading Adam Bede and Middlemarch be justified in this time of climate change, financial meltdown and ineffective politicians? J. Hillis Miller shows how, to be read for today, they must be read ...slowly, closely and carefully, with much attention to linguistic detail and especially to figures of speech. By relating mistakes like Dorothea's about Casaubon to current affairs, Miller's 'readings for today' can help us to come to terms with our human, social and political situation and even inspire us to act to ameliorate it.
The COVID-19 pandemic and related restrictions led to major transit demand decline for many public transit systems in the United States. This paper is a systematic analysis of the dynamics and ...dimensions of this unprecedented decline. Using transit demand data derived from a widely used transit navigation app, we fit logistic functions to model the decline in daily demand and derive key parameters: base value, the apparent minimal level of demand and cliff and base points, representing the initial date when transit demand decline began and the final date when the decline rate attenuated. Regression analyses reveal that communities with higher proportions of essential workers, vulnerable populations (African American, Hispanic, Female, and people over 45 years old), and more coronavirus Google searches tend to maintain higher levels of minimal demand during COVID-19. Approximately half of the agencies experienced their decline before the local spread of COVID-19 likely began; most of these are in the US Midwest. Almost no transit systems finished their decline periods before local community spread. We also compare hourly demand profiles for each system before and during COVID-19 using ordinary Procrustes distance analysis. The results show substantial departures from typical weekday hourly demand profiles. Our results provide insights into public transit as an essential service during a pandemic.
A Concise History of Mycotoxin Research Pitt, John I; Miller, J. David
Journal of agricultural and food chemistry,
08/2017, Volume:
65, Issue:
33
Journal Article
Peer reviewed
Toxigenic fungi and mycotoxins entered human food supplies about the time when mankind first began to cultivate crops and to store them from one season to the next, perhaps 10,000 years ago. The ...storage of cereals probably initiated the transition by mankind from hunter-gatherer to cultivator, at the same time providing a vast new ecological niche for fungi pathogenic on grain crops or saprophytic on harvested grain, many of which produced mycotoxins. Grains have always been the major source of mycotoxins in the diet of man and his domestic animals. In the historical context, ergotism from Claviceps purpurea in rye has been known probably for more than 2000 years and caused the deaths of many thousands of people in Europe in the last millennium. Known in Japan since the 17th century, acute cardiac beriberi associated with the consumption of moldy rice was found to be due to citreoviridin produced by Penicillium citreonigrum. This toxin was believed to be only of historic importance until its reemergence in Brazil a few years ago. Other Penicillium toxins, including ochratoxin A, once considered to be a possible cause of Balkan endemic nephropathy, are treated in a historical context. The role of Fusarium toxins in human and animal health, especially T-2 toxin in alimentary toxic aleukia in Russia in the 1940s and fumonisins in equine leucoencephalomalasia, is set out in some detail. Finally, this paper documents the story of the research that led to our current understanding of the formation of aflatoxins in grains and nuts, due to the growth of Aspergillus flavus and its role, in synergy with the hepatitis B virus, in human liver cancer. During a period of climate change and greatly reduced crop diversity on a global basis, researchers tasked with monitoring the food system need to be aware of fungal toxins that might have been rare in their working careers that can reappear.
Astrocytes are the most abundant cell type in the central nervous system (CNS), providing critical roles in the overall maintenance and homeostasis. Over 100 years ago, Cajal first showed ...morphological depictions of different astrocyte populations. Surprisingly, to date astrocytes remain classified in two groups based on their morphological and neuroanatomical positioning. However, accumulating evidence over the past few years is showing that astrocytes are highly diverse throughout the CNS. Astrocyte heterogeneity is not surprisingly, as these cells interact with all other cells in the CNS. Like neurons, astrocytes may also have subpopulations that vary in their functionality. In this mini review, we will explore some of the recent evidence in the adult CNS of astrocyte diversity. First, we will review the very little literature on healthy adult astroglia heterogeneity, followed by the identification of different subpopulations in disease states and how this varies between human and mouse. Exploring this new area of neuroscience will hopefully provide researchers with a new perspective on astrocytes and their heterogeneity throughout the CNS.
Conspectus Nature’s catalytic machinery has provided endless inspiration for chemists. While the enzymatic ideal has yet to be fully realized, the field has made tremendous strides toward synthetic, ...small-molecule catalysts for a wide array of transformations, often drawing upon biological concepts in their design. One strategy that has been particularly influenced by enzymology is peptide catalysis, wherein oligopeptides are implemented as chiral catalysts in synthetically relevant reactions. The fundamental goal has been to mimic enzymatic active sites by taking advantage of secondary structures that allow for multifunctional activation of substrates within a framework of significantly reduced molecular complexity. Our group has now been studying peptide-based catalysis for over two decades. At the outset, there were many reasons to be concerned that general contributions might not be possible. Precedents existed, including the Juliá–Colonna epoxidations mediated by helical oligopeptides, among others. However, we sought to explore whether peptide catalysts could find broad applications in organic synthesis despite what was expected to be their principal liability: conformational flexibility. Over time, we have been able to identify peptidic catalysts for a variety of site- and enantioselective transformations ranging from hydroxyl group and arene functionalizations to redox and C–C bond forming reactions. The peptides often exhibited excellent catalytic activities, in many cases enabling never-before-seen patterns of selectivity. Recent studies even suggest that, in certain situations, the conformational flexibility of these catalysts may be advantageous for asymmetric induction. In the course of our studies, opportunities to employ peptide-based catalysis to solve long-standing and stereochemically intriguing problems in asymmetric synthesis presented themselves. For example, we have found that peptides provide exceptional enantiotopic group differentiation in catalytic desymmetrization reactions. Early results with symmetrical polyol substrates, such as myo-inositols and glycerols, eventually spurred the development of remote desymmetrizations of diarylmethanes, in which the enantiotopic groups are separated from the prochiral center by ∼6 Å and from one another by nearly 1 nm. Various hydroxyl group functionalizations and electrophilic brominations, as well as C–C, C–O, and C–N cross-coupling reactions using peptidic ligands on copper(I) have now been developed within this reaction archetype. Additionally, the preponderance of axially chiral, atropisomeric compounds as ligands, organocatalysts, and pharmacophores encouraged us to employ peptides as atroposelective catalysts. We have developed peptide-catalyzed brominations of pharmaceutically relevant biaryl, non-biaryl, and hetero-biaryl atropisomers that take advantage of dynamic kinetic resolution schemes. These projects have vastly expanded the reach of our original hypotheses and raised new questions about peptide-based catalysts and the extent to which they might mimic enzymes. Herein, we recount the development and optimization of these stereochemically complex reactions, with a particular focus on structural and mechanistic aspects of the peptide-based catalysts that make them well-suited for their respective functions. The ability of these peptides to address important yet fundamentally challenging issues in asymmetric catalysis, combined with their modularity and ease-of-synthesis, make them primed for future use in organic synthesis.
Schizophrenia, bipolar disorder and major depressive disorder (MDD) have all been associated with aberrant blood cytokine levels; however, neither the pattern of cytokine alterations nor the impact ...of clinical status have been compared across disorders. We performed a meta-analysis of blood cytokines in acutely and chronically ill patients with these major psychiatric disorders. Articles were identified by searching the PubMed, PsycInfo and Web of Science, and the reference lists of these studies. Sixty-eight studies met the inclusion criteria (40 schizophrenia, 10 bipolar disorder and 18 MDD) for acutely ill patients. Forty-six studies met the inclusion criteria (18 schizophrenia, 16 bipolar disorder and 12 MDD) for chronically ill patients. Levels of two cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), one soluble cytokine receptor (sIL-2R), and one cytokine receptor antagonist (IL-1RA) were significantly increased in acutely ill patients with schizophrenia, bipolar mania and MDD compared with controls (P<0.01). Following treatment of the acute illness, IL-6 levels significantly decreased in both schizophrenia and MDD (P<0.01); sIL-2R levels increased in schizophrenia; and IL-1RA levels in bipolar mania decreased. In chronically ill patients, the levels of IL-6 were significantly increased in schizophrenia, euthymic (but not depressed) bipolar disorder and MDD compared with controls (P<0.01). The levels of IL-1β and sIL-2R were significantly increased in both chronic schizophrenia and euthymic bipolar disorder. Overall, there were similarities in the pattern of cytokine alterations in schizophrenia, bipolar disorder and MDD during acute and chronic phases of illness, raising the possibility of common underlying pathways for immune dysfunction. Effects of treatment on cytokines were more robust for schizophrenia and MDD, but were more frequently studied than for acute mania. These findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.
Crop productivity relies heavily on nitrogen (N) fertilization. Production and application of N fertilizers consume huge amounts of energy, and excess is detrimental to the environment; therefore, ...increasing plant N use efficiency (NUE) is essential for the development of sustainable agriculture. Plant NUE is inherently complex, as each step-including N uptake, translocation, assimilation, and remobilization-is governed by multiple interacting genetic and environmental factors. The limiting factors in plant metabolism for maximizing NUE are different at high and low N supplies, indicating great potential for improving the NUE of current cultivars, which were bred in well-fertilized soil. Decreasing environmental losses and increasing the productivity of crop-acquired N requires the coordination of carbohydrate and N metabolism to give high yields. Increasing both the grain and N harvest index to drive N acquisition and utilization are important approaches for breeding future high-NUE cultivars.
A new radio census of neutron star X-ray binaries van den Eijnden, J; Degenaar, N; Russell, T D ...
Monthly notices of the Royal Astronomical Society,
11/2021, Volume:
507, Issue:
3
Journal Article
Peer reviewed
Open access
ABSTRACT
We report new radio observations of a sample of 36 neutron star (NS) X-ray binaries, more than doubling the sample in the literature observed at current-day sensitivities. These sources ...include 13 weakly magnetized (B < 1010 G) and 23 strongly magnetized (B ≥ 1010 G) NSs. 16 of the latter category reside in high-mass X-ray binaries, of which only two systems were radio-detected previously. We detect four weakly and nine strongly magnetized NSs; the latter are systematically radio fainter than the former and do not exceed LR ≈ 3 × 1028 erg s−1. In turn, we confirm the earlier finding that the weakly magnetized NSs are typically radio fainter than accreting stellar-mass black holes. While an unambiguous identification of the origin of radio emission in high-mass X-ray binaries is challenging, we find that in all but two detected sources (Vela X-1 and 4U 1700-37) the radio emission appears more likely attributable to a jet than the donor star wind. The strongly magnetized NS sample does not reveal a global correlation between X-ray and radio luminosity, which may be a result of sensitivity limits. Furthermore, we discuss the effect of NS spin and magnetic field on radio luminosity and jet power in our sample. No current model can account for all observed properties, necessitating the development and refinement of NS jet models to include magnetic field strengths up to 1013 G. Finally, we discuss jet quenching in soft states of NS low-mass X-ray binaries, the radio non-detections of all observed very-faint X-ray binaries in our sample, and future radio campaigns of accreting NSs.
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