1,597 research outputs found

    Francis Ellington\u27s use of Prophecy to Explain the Appearance, Deliverance, and Apocalyptic Role of Quakers in the Last Days

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    Early Quakers rarely relied on ancient or modern (seventeenth century) prophecy to authenticate their faith. The reason for this was their emphasis on inner revelation. After the Nayler episode Quakers slowly began to turn their energies toward making necessary theological and institutional adjustments that would better enable the movement to control the radical individualism of the inner light. One area that has not received much attention is how attitudes toward prophecy were changing. This paper focuses on one distinctive Quaker pamphlet which appeared in 1664. Francis Ellington\u27s A Christian Information Conce��ning These Last Times demonstrates how one Quaker was strugglmg to understand the reasons for the long-delayed consummation of the Lamb\u27s War. In the face of fierce persecution and the difficult conditions for Quakers during the Restoration Ellington searched back beyond Fox for new expressions of prophetic authentication and encouragement. The use of specific prophecy, now seen as coming true, was rare in Quaker writing. Ellington\u27s voice may have been a distinctive one among Quakers of the time but his tendency to incorporate a pacifist element into a militant apocalyptic rhetoric was not unusual in Quaker writing until the 1680s

    The Mechanical Properties of Bacteria through the Cell Cycle as Measured by Atomic Force Microscopy

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    Staphylococcus aureus (SA) is a major cause of infection in humans, including the Methicillin resistant strain, MRSA. However, very little is known about the mechanical properties of these cells. The investigations presented in this thesis use Atomic Force Microscopy (AFM) to examine live SA cells to quantify their mechanical properties. These were explored using force spectroscopy with different trigger forces, allowing the properties to be extracted at different indentation depths. A value obtained with sharp silicon tips of (0.0134 +/-� 0.0068) Nm^�1 for the cell wall stiffness has been extracted, along with a second, higher value of (0.2062 �+/- 0.0039) Nm^�1 which is found upon indenting at higher forces. This higher value drops by a factor of more than 4 when the cells are exposed to high salt, sugar and detergent concentrations, implying that this measurement contains a contribution from the internal turgor pressure of the cell. These properties were monitored as the cells progressed through the cell cycle. Force maps were taken over the cells at different stages of the growth process to identify changes in the mechanics throughout the progression of growth and division. These experiments revealed no measurable change in the turgor pressure of the cell, as measured in this way, but it was found that newly formed areas of cell wall exposed for the first time during the separation of daughter cells gave a higher measured stiffness. This can be related to the structure of the cell wall, which changes as the newly formed cell wall matures during the development of the daughter cells. The effect of a b-lactam antibiotic, Oxacillin, has also been studied, in an attempt to better understand its mechanism of action. This class of drug is understood to work during division, preventing successful reproduction by inhibiting cell wall production leading to cell lysis. Images were taken throughout the process of b-lactam induced cell death for the �first time. Finally mutant strains of SA and a second species, Bacillus subtilis (BS), have been used to link the mechanical properties of the cell walls to structural alterations. Both of these groups of cells contain varied cell wall glycan chain lengths, allowing the study of the effect of chain length on the measured mechanical properties

    Electronic Spectroscopy of Chloro(terpyridine)platinum(II)

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    The electronic spectrum of [Pt(tpy)Cl]^+ (tpy = 2,2':6',2"-terpyridine) is influenced dramatically by intermolecular stacking interactions in solution and in the solid state. The crystal structure of [Pt(tpy)Cl]ClO_4 (monoclinic, P2_1/c (No. 14); a = 7.085(2), b = 17.064(5), c = 26.905(8) Å; β = 90.0(1) °; Z = 8) consists of discrete Pt_2 units (Pt-Pt = 3.269(1) Å) arranged along an infinite tpy-π stack (spacing ~ 3.35 Å). Variable-temperature and concentration studies of the absorption and emission spectra of [Pt(tpy)Cl]^+ suggest that similar metal-metal and ligand-ligand interactions persist in the solution phase. The high concentration, low-temperature emission spectrum (5:5:1 ethanol:methanol:DMF) reveals a 740-nm band indicative of M-M oligomerization, a 650-nm band attributable to tpy π-π interactions, and a 470-nm band characteristic of mononuclear [Pt(tpy)Cl]^+ π-π* emission. Concentration-dependent absorption spectra were fit to a "two-dimer" model, yielding equilibrium constants for the formation of Pt-Pt-, and tpy-tpy-bound dimers of 1.3(1) x 10^3 and 1.0(1) x 10^3 M^(-1), respectively, in 0.1 M aqueous NaCl. The low temperature solid-state luminescence of [Pt(tpy)Cl]^+ is assigned to a ^3(MMLCT) (MMLCT = metal-metal-to-ligand charge transfer) transition. The energy of this band is highly dependent on the counterion (PF_6^-, ClO_4^- , C1^-, CF_3SO_3^-), in line with the different colors of these various salts. In contrast, the room-temperature solid-state emission spectra are more difficult to interpret. While the red perchlorate salt exhibits a relatively narrow emission band at 725 nm (red-shifted from the 77-K maximum at 695 nm), consistent with a 3(MMLCT) transition, the orange (Cl^-, ClO_4^-, CF_3SO_3^-) and yellow (PF6^-) salts have extremely broad room-temperature emission bands that all appear at nearly the same energy (λ_(max) ~ 640 nm). We assign this luminescence to an eximeric intraligand transition resulting from π- π interactions and propose that the temperature dependent emissions from the orange and yellow solid materials originate from multiple electronic states

    Modular Nucleic Acid Assembled p/MHC Microarrays for Multiplexed Sorting of Antigen-Specific T Cells

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    The human immune system consists of a large number of T cells capable of recognizing and responding to antigens derived from various sources. The development of peptide-major histocompatibility (p/MHC) tetrameric complexes has enabled the direct detection of these antigen-specific T cells. With the goal of increasing throughput and multiplexing of T cell detection, protein microarrays spotted with defined p/MHC complexes have been reported, but studies have been limited due to the inherent instability and reproducibility of arrays produced via conventional spotted methods. Herein, we report on a platform for the detection of antigen-specific T cells on glass substrates that offers significant advantages over existing surface-bound schemes. In this approach, called “Nucleic Acid Cell Sorting (NACS)”, single-stranded DNA oligomers conjugated site-specifically to p/MHC tetramers are employed to immobilize p/MHC tetramers via hybridization to a complementary-printed substrate. Fully assembled p/MHC arrays are used to detect and enumerate T cells captured from cellular suspensions, including primary human T cells collected from cancer patients. NACS arrays outperform conventional spotted arrays assessed in key criteria such as repeatability and homogeneity. The versatility of employing DNA sequences for cell sorting is exploited to enable the programmed, selective release of target populations of immobilized T cells with restriction endonucleases for downstream analysis. Because of the performance, facile and modular assembly of p/MHC tetramer arrays, NACS holds promise as a versatile platform for multiplexed T cell detection

    Design studies of large aperture, high-resolution Earth science microwave radiometers compatible with small launch vehicles

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    High-spatial-resolution microwave radiometer sensing from space with reasonable swath widths and revisit times favors large aperture systems. However, with traditional precision antenna design, the size and weight requirements for such systems are in conflict with the need to emphasize small launch vehicles. This paper describes tradeoffs between the science requirements, basic operational parameters, and expected sensor performance for selected satellite radiometer concepts utilizing novel lightweight compactly packaged real apertures. Antenna, feed, and radiometer subsystem design and calibration are presented. Preliminary results show that novel lightweight real aperture coupled with state-of-the-art radiometer designs are compatible with small launch systems, and hold promise for high-resolution earth science measurements of sea ice, precipitation, soil moisture, sea surface temperature, and ocean wind speeds

    ‘Fit for surgery’:the relationship between cardiorespiratory fitness and postoperative outcomes

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    NEW FINDINGS: What is the topic of this review? The relationships and physiological mechanisms underlying the clinical benefits of cardiorespiratory fitness (CRF) in patients undergoing major intra‐abdominal surgery. What advances does it highlight? Elevated CRF reduces postoperative morbidity/mortality, thus highlighting the importance of CRF as an independent risk factor. The vascular protection afforded by exercise prehabilitation can further improve surgical risk stratification and postoperative outcomes. ABSTRACT: Surgery accounts for 7.7% of all deaths globally and the number of procedures is increasing annually. A patient's ‘fitness for surgery’ describes the ability to tolerate a physiological insult, fundamental to risk assessment and care planning. We have evolved as obligate aerobes that rely on oxygen (O(2)). Systemic O(2) consumption can be measured via cardiopulmonary exercise testing (CPET) providing objective metrics of cardiorespiratory fitness (CRF). Impaired CRF is an independent risk factor for mortality and morbidity. The perioperative period is associated with increased O(2) demand, which if not met leads to O(2) deficit, the magnitude and duration of which dictates organ failure and ultimately death. CRF is by far the greatest modifiable risk factor, and optimal exercise interventions are currently under investigation in patient prehabilitation programmes. However, current practice demonstrates potential for up to 60% of patients, who undergo preoperative CPET, to have their fitness incorrectly stratified. To optimise this work we must improve the detection of CRF and reduce potential for interpretive error that may misinform risk classification and subsequent patient care, better quantify risk by expressing the power of CRF to predict mortality and morbidity compared to traditional cardiovascular risk factors, and improve patient interventions with the capacity to further enhance vascular adaptation. Thus, a better understanding of CRF, used to determine fitness for surgery, will enable both clinicians and exercise physiologists to further refine patient care and management to improve survival

    Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4

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    Background: The cytochrome P450 3A4 (CYP3A4) inhibitor clarithromycin may also inhibit liverspecific organic anion-transporting polypeptides (OATP1B1 and OATP1B3). We studied whether concurrent use of clarithromycin and a statin not metabolized by CYP3A4 was associated with an increased frequency of serious adverse events. Methods: Using large health care databases, we studied a population-based cohort of older adults (mean age 74 years) who were taking a statin not metabolized by CYP3A4 (rosuvastatin [76% of prescriptions], pravastatin [21%] or fluvastatin [3%]) between 2002 and 2013 and were newly prescribed clarithromycin (n = 51 523) or azithromycin (n = 52 518), the latter an antibiotic that inhibits neither CYP3A4 nor OATP1B1 and OATP1B3. Outcomes were hospital admission with a diagnostic code for rhabdomyolysis, acute kidney injury or hyperkalemia, and allcause mortality. All outcomes were assessed within 30 days after co-prescription. Results: Compared with the control group, patients co-prescribed clarithromycin and a statin not metabolized by CYP3A4 were at increased risk of hospital admission with acute kidney injury (adjusted relative risk [RR] 1.65, 95% confidence interval [CI] 1.31 to 2.09), admission with hyperkalemia (adjusted RR 2.17, 95% CI 1.22 to 3.86) and all-cause mortality (adjusted RR 1.43, 95% CI 1.15 to 1.76). The adjusted RR for admission with rhabdomyolysis was 2.27 (95% CI 0.86 to 5.96). The absolute increase in risk for each outcome was small and likely below 1%, even after we considered the insensitivity of some hospital database codes. Interpretation: Among older adults taking a statin not metabolized by CYP3A4, co-prescription of clarithromycin versus azithromycin was associated with a modest but statistically significant increase in the 30-day absolute risk of adverse outcomes
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