The Orc Symbol in William Blake\u27s Works

A study of Orc, Blake\u27s symbol for energy, suggests several different hypotheses. This paper intends to test the hypothesis that Orc is a force. With the use of illustrations and explications, Orc becomes more clearly a symbol of Blake\u27s imaginative form. This energy will be seen at each level of Blake\u27s visions, each different psychological stage, and at the highest level, poetic imagination. Thus, as the creator creates, the creation becomes the molded form of the creator\u27s imagination

Scale-free bursting in human cortex following hypoxia at birth

The human brain is fragile in the face of oxygen deprivation. Even a briefinterruption of metabolic supply at birth challenges an otherwise healthy neonatal cortex, leading to a cascade of homeostatic responses. During recovery from hypoxia, cortical activity exhibits a period of highly irregular electrical fluctuations known as burst suppression. Here we show that these bursts have fractal properties, with power-law scaling of burst sizes across a remarkable 5 orders of magnitude and a scale-free relationship between burst sizes and durations. Although burst waveforms vary greatly, their average shape converges to a simple form that is asymmetric at long time scales. Using a simple computational model, we argue that this asymmetry reflects activity-dependent changes in the excitatory-inhibitory balance of cortical neurons. Bursts become more symmetric following the resumption of normal activity, with a corresponding reorganization of burst scaling relationships. These findings place burst suppression in the broad class of scale-free physical processes termed crackling noise and suggest that the resumption of healthy activity reflects a fundamental reorganization in the relationship between neuronal activity and its underlying metabolic constraints

ISU Faculty Woodwind Quintet Concert: Mary Finnigan, Flute; David R. Sheaffer, Oboe; Herbert Sanders, Clarinet; Philip HIllstrom, French Horn; James Thornton, Bassoon; April 22, 1971

Capen AuditoriumThursdayApril 22, 19718:15 p.m

Local elites and social control: Building council houses in Stirling between the wars

This article examines the role played by local councillors in constructing new housing in Scotland during the inter-war period. Rather than view local authorities as simply the objective agency of central government's ambitions to construct council houses, we argue that the self-interest and motivations of councillors have to be recognized as significant factors in this process. It is argued also that the concerns of private landlords were neither ignored nor sacrificed in the rush to build new housing. Rather, given that councils remained dominated by local business men, many of whom were private landlords, councillors acted in ways to protect their own material and class interests. In so doing, they consciously, if implicitly, shaped the social geography of twentieth-century Scotland

Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study

Background ‘Long COVID’ describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models along with certain clinical conditions, and therefore may reduce fatigue associated with Long COVID. We aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID. Methods Patients with fatigue-dominant Long COVID were recruited in this single-centre, double-blind, randomised controlled phase 2a pilot study completed in the UK. Patients were randomly assigned (1:1) using an Interactive Response Technology to receive either AXA1125 or matching placebo in a clinical-based setting. Each dose (33.9 g) of AXA1125 or placebo was administered orally in a liquid suspension twice daily for four weeks with a two-week follow-up period. The primary endpoint was the mean change from baseline to day 28 in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by 31P-magnetic resonance spectroscopy (MRS). All patients were included in the intention to treat analysis. This trial was registered at ClinicalTrials.gov, NCT05152849. Findings Between December 15th 2021, and May 23th 2022, 60 participants were screened, and 41 participants were randomised and included in the final analysis. Changes in skeletal muscle phosphocreatine recovery time constant (τPCr) and 6-min walk test (6MWT) did not significantly differ between treatment (n = 21) and placebo group (n = 20). However, treatment with AXA1125 was associated with significantly reduced day 28 Chalder Fatigue Questionnaire [CFQ-11] fatigue score when compared with placebo (least squares mean difference [LSMD] −4.30, 95% confidence interval (95% CI) −7.14, −1.47; P = 0.0039). Eleven (52.4%, AXA1125) and four (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious or led to treatment discontinuation. Interpretation Although treatment with AXA1125 did not improve the primary endpoint (τPCr-measure of mitochondrial respiration), when compared to placebo, there were significant improvements in fatigue-based symptoms among patients living with Long COVID following a four-week treatment period. Further multicentre studies are needed to validate our findings in a larger cohort of patients with fatigue-dominant Long COVID. Funding Axcella Therapeutics

Novel features of early burst suppression predict outcome after birth asphyxia

Peer reviewe

Synthesis of Stereoenriched Piperidines via Chemo- Enzymatic Dearomatization of Activated Pyridines

The development of efficient and sustainable methods for the synthesis of nitrogen heterocycles is an important goal for the chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds and their precursors. A potential biocatalytic approach to the synthesis of this privileged scaffold would be the asymmetric dearomatization of readily assembled activated pyridines. However, nature has yet to yield a suitable biocatalyst specifically for this reaction. Here, by combining chemical synthesis and biocatalysis, we present a general chemo-enzymatic approach for the asymmetric dearomatization of activated pyridines for the preparation of substituted piperidines with precise stereochemistry. The key step involves a stereoselective one-pot amine oxidase/ene imine reductase cascade to convert N-substituted tetrahydropyridines to stereo-defined 3- and 3,4-substituted piperidines. This chemo-enzymatic approach has proved useful for key transformations in the syntheses of the antipsychotic drugs Preclamol and OSU-6162, as well as for the preparation of two important intermediates in synthetic routes of the ovarian cancer monotherapeutic Niraparib

An engineered cytidine deaminase for biocatalytic production of a key intermediate of the COVID-19 antiviral Molnupiravir

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Local Earthquake Magnitude Scale and b‐Value for the Danakil Region of Northern Afar

The Danakil region of northern Afar is an area of ongoing seismic and volcanic activity caused by the final stages of continental breakup. To improve the quantification of seismicity, we developed a calibrated local earthquake magnitude scale. The accurate calculation of earthquake magnitudes allows the estimation of b?values and maximum magnitudes, both of which are essential for seismic?hazard analysis. Earthquake data collected between February 2011 and February 2013 on 11 three?component broadband seismometers were analyzed. A total of 4275 earthquakes were recorded over hypocentral distances ranging from 0 to 400 km. A total of 32,904 zero?to?peak amplitude measurements (A) were measured on the seismometer’s horizontal components and were incorporated into a direct linear inversion that solved for all individual local earthquake magnitudes (ML), 22 station correction factors (C), and 2 distance?dependent factors (n, K) in the equation ML=log(A)?log(A0)+C. The resultant distance correction term is given by ?log(A0)=1.274336log(r/17)?0.000273(r?17)+2. This distance correction term suggests that attenuation in the upper and mid?crust of northern Afar is relatively high, consistent with the presence of magmatic intrusions and partial melt. In contrast, attenuation in the lower crust and uppermost mantle is anomalously low, interpreted to be caused by a high melt fraction causing attenuation to occur outside the seismic frequency band. The calculated station corrections serve to reduce the ML residuals significantly but do not show a correlation with regional geology. The cumulative seismicity rate produces a b?value of 0.9±0.06, which is higher than most regions of continental rifting yet lower than values recorded at midocean ridges, further supporting the hypothesis that northern Afar is transitioning to seafloor spreading