Direct observation of substrate binding to ferrous-CO cytochrome P-450-CAM using 19F NMR

AbstractThe binding of two fluorinated substrate analogs, 9-fluorocamphor and 5,5-difluorocamphor, to cytochrome P-450-CAM has been investigated by 19F NMR spectroscopy. The NMR properties of each substrate differ depending on whether it is free in aqueous buffer, bound to the diamagnetic ferrous-CO enzyme or bound to the paramagnetic ferrous derivative. As CO must be bound to the ferrous center for it to be diamagnetic, these results demonstrate that camphor and CO bind to the protein simultaneously. The present results are unusual in that the spectral properties of the substrate rather than those of the heme iron have been monitored to follow substrate and ligand binding

Interview with Half Century Club Inductees, Class of 1930

Oral history interview with Illinois State Normal University alumni, Class of 1930. The interview was conducted on May 10, 1980, by an unidentified interviewer. They discuss President Felmley, influential faculty, and racial discrimination experienced by students of color.https://ir.library.illinoisstate.edu/aoh/1002/thumbnail.jp

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Quantification of water states in thin proton exchange membrane manufacturing using terahertz time-domain spectroscopy

Water states in proton exchange membranes have previously been extracted using terahertz time-domain spectroscopy (THz-TDS) for thick Nafion membranes. In this work, we have developed a parametric based algorithm for data analysis and applied it to thin industrially relevant membranes (13-70μm), processed under different conditions, producing results consistent with conventional gravimetric analysis and prior demonstrations. This therefore opens up opportunities for rapid membrane investigations and understanding

Phase equilibria and glass transition in colloidal systems with short-ranged attractive interactions. Application to protein crystallization

We have studied a model of a complex fluid consisting of particles interacting through a hard core and a short range attractive potential of both Yukawa and square-well form. Using a hybrid method, including a self-consistent and quite accurate approximation for the liquid integral equation in the case of the Yukawa fluid, perturbation theory to evaluate the crystal free energies, and mode-coupling theory of the glass transition, we determine both the equilibrium phase diagram of the system and the lines of equilibrium between the supercooled fluid and the glass phases. For these potentials, we study the phase diagrams for different values of the potential range, the ratio of the range of the interaction to the diameter of the repulsive core being the main control parameter. Our arguments are relevant to a variety of systems, from dense colloidal systems with depletion forces, through particle gels, nano-particle aggregation, and globular protein crystallization.Comment: 20 pages, 10 figure

High-resolution volumetric imaging constrains compartmental models to explore synaptic integration and temporal processing by cochlear nucleus globular bushy cells

Globular bushy cells (GBCs) of the cochlear nucleus play central roles in the temporal processing of sound. Despite investigation over many decades, fundamental questions remain about their dendrite structure, afferent innervation, and integration of synaptic inputs. Here, we use volume electron microscopy (EM) of the mouse cochlear nucleus to construct synaptic maps that precisely specify convergence ratios and synaptic weights for auditory- nerve innervation and accurate surface areas of all postsynaptic compartments. Detailed biophysically-based compartmental models can help develop hypotheses regarding how GBCs integrate inputs to yield their recorded responses to sound. We established a pipeline to export a precise reconstruction of auditory nerve axons and their endbulb terminals together with high-resolution dendrite, soma, and axon reconstructions into biophysically-detailed compartmental models that could be activated by a standard cochlear transduction model. With these constraints, the models predict auditory nerve input profiles whereby all endbulbs onto a GBC are subthreshold (coincidence detection mode), or one or two inputs are suprathreshold (mixed mode). The models also predict the relative importance of dendrite geometry, soma size, and axon initial segment length in setting action potential threshold and generating heterogeneity in sound-evoked responses, and thereby propose mechanisms by which GBCs may homeostatically adjust their excitability. Volume EM also reveals new dendritic structures and dendrites that lack innervation. This framework defines a pathway from subcellular morphology to synaptic connectivity, and facilitates investigation into the roles of specific cellular features in sound encoding. We also clarify the need for new experimental measurements to provide missing cellular parameters, and predict responses to sound for further in vivo studies, thereby serving as a template for investigation of other neuron classes

Measurements of Secondary Cosmic Microwave Background Anisotropies with the South Pole Telescope

We report cosmic microwave background (CMB) power spectrum measurements from the first 100 sq. deg. field observed by the South Pole Telescope (SPT) at 150 and 220 GHz. On angular scales where the primary CMB anisotropy is dominant, ell ~< 3000, the SPT power spectrum is consistent with the standard LambdaCDM cosmology. On smaller scales, we see strong evidence for a point source contribution, consistent with a population of dusty, star-forming galaxies. After we mask bright point sources, anisotropy power on angular scales of 3000 50 at both frequencies. We combine the 150 and 220 GHz data to remove the majority of the point source power, and use the point source subtracted spectrum to detect Sunyaev-Zel'dovich (SZ) power at 2.6 sigma. At ell=3000, the SZ power in the subtracted bandpowers is 4.2 +/- 1.5 uK^2, which is significantly lower than the power predicted by a fiducial model using WMAP5 cosmological parameters. This discrepancy may suggest that contemporary galaxy cluster models overestimate the thermal pressure of intracluster gas. Alternatively, this result can be interpreted as evidence for lower values of sigma8. When combined with an estimate of the kinetic SZ contribution, the measured SZ amplitude shifts sigma8 from the primary CMB anisotropy derived constraint of 0.794 +/- 0.028 down to 0.773 +/- 0.025. The uncertainty in the constraint on sigma8 from this analysis is dominated by uncertainties in the theoretical modeling required to predict the amplitude of the SZ power spectrum for a given set of cosmological parameters.Comment: 28 pages, 11 figures, submitted to Ap

Using VO tools to investigate distant radio starbursts hosting obscured AGN in the HDF(N) region

A 10-arcmin field around the HDF(N) contains 92 radio sources >40 uJy, resolved by MERLIN+VLA at 0".2-2".0 resolution. 55 have Chandra X-ray counterparts including 18 with a hard X-ray photon index and high luminosity characteristic of a type-II (obscured) AGN. >70% of the radio sources have been classified as starbursts or AGN using radio morphologies, spectral indices and comparisons with optical appearance and MIR emission. Starbursts outnumber radio AGN 3:1. This study extends the VO methods previously used to identify X-ray-selected obscured type-II AGN to investigate whether very luminous radio and X-ray emission originates from different phenomena in the same galaxy. The high-redshift starbursts have typical sizes of 5--10 kpc and star formation rates of ~1000 Msun/yr. There is no correlation between radio and X-ray luminosities nor spectral indices at z>~1.3. ~70% of both the radio-selected AGN and the starburst samples were detected by Chandra. The X-ray luminosity indicates the presence of an AGN in at least half of the 45 cross-matched radio starbursts, of which 11 are type-II AGN including 7 at z>1.5. This distribution overlaps closely with the X-ray detected radio sources which were also detected by SCUBA. Stacked 1.4-GHz emission at the positions of radio-faint X-ray sources is correlated with X-ray hardness. Most extended radio starbursts at z>1.3 host X-ray selected obscured AGN. Radio emission from most of these ultra-luminous objects is dominated by star formation but it contributes less than 1/3 of their X-ray luminosity. Our results support the inferences from SCUBA and IR data, that at z>1.5, star formation is an order of magnitude more extended and more copious, it is closely linked to AGN activity and it is triggered differently, compared with star formation at lower redshifts.Comment: 24 pages, 12 figures, uses graphicx, rotating, natbib, supertabular packages and aa.cls. Accepted for publication in A&

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Thermoregulation and heterothermy in some of the smaller flying foxes (Megachiroptera) of New Guinea

Body temperature, heterothermy, oxygen consumption, heart rate, and evaporative water loss were studied in four species of flying foxes (Megachiroptera), Dobsonia minor, Nyctimene major, Nyctimene albiventer , and Paranyctimene raptor , from the vicinity of Madang on the north coast of New Guinea.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47105/1/359_2004_Article_BF00297716.pd