1,488 research outputs found
History and Silence. Purge and the Rehabilitation of Memory in Late Antiquity.
In AD 431 a statue of the senator Virius Nicomachus Flavianus was erected in Trajanâs Forum at Rome. On its base was inscribed an imperial letter that rehabilitated Flavianusâ reputation (CIL 6. 1783). Flavianus had committed suicide after the usurper Eugenius, whose revolt he had supported, was defeated in 394. In the aftermath, Flavianus was subject to damnatio memoriae for his part in the rebellion. This disgrace and subsequent rehabilitation form the theme of H.âs study, which has at its heart a study of the inscription on the statue base
History and Silence. Purge and the Rehabilitation of Memory in Late Antiquity.
In AD 431 a statue of the senator Virius Nicomachus Flavianus was erected in Trajanâs Forum at Rome. On its base was inscribed an imperial letter that rehabilitated Flavianusâ reputation (CIL 6. 1783). Flavianus had committed suicide after the usurper Eugenius, whose revolt he had supported, was defeated in 394. In the aftermath, Flavianus was subject to damnatio memoriae for his part in the rebellion. This disgrace and subsequent rehabilitation form the theme of H.âs study, which has at its heart a study of the inscription on the statue base
Biodegradable cationic poly(carbonates): effect of varying side chain hydrophobicity on key aspects of gene transfection
The degree of hydrophobicity in cationic polymers plays an important but often underappreciated role in the safety and efficacy of gene delivery processes. In order to further elucidate structure-activity relationships of biodegradable cationic poly(carbonate) gene carriers, we synthesized a series of narrowly dispersed homo-polymers via metal-free organocatalytic living ring-opening polymerization (ROP) of cyclic carbonate monomers bearing either alkyl (propyl, hexyl or nonyl) or 4-methyl benzyl halide side chains. The polymers were then quaternized using bis-tertiary amines to install both quaternary ammoniums and tertiary amines for DNA binding and endosomal escape, respectively. Among the polymers with similar molecular lengths and charge densities, it was found that an increase in side chain alkyl spacer length from 3 to 6 carbons significantly enhanced cellular uptake and luciferase gene expression in HepG2 and HeLa cell lines without causing overt hemolysis and cytotoxicity. A further increase of side chain alkyl length to 9 carbons, however, led to a drastic decline in gene expression due to increased cellular toxicity, which was correlated with an increased disruption and lysis of red blood cell membranes. Interestingly, the incorporation of an aromatic 4-methyl benzyl spacer increased DNA binding strength, reduced particle sizes of resultant DNA complexes, and enhanced cellular uptake, leading to improved luciferase gene expression, albeit with higher levels of hemolysis and cytotoxicity. Taken together, the findings of this study demonstrate that a delicate balance between cationic charge density and hydrophobicity could be achieved by utilizing a hexyl spacer in the side chains of cationic poly(carbonates), hence providing insights on the future development of non-viral cationic polymeric gene delivery systems. Statement of Significance: Owing to their ease of synthesis and well-controlled polymerization, biodegradable cationic poly(carbonates) have emerged as a highly promising class of biomaterials for gene delivery. The hydrophobicity of side chains in cationic polymers plays an important but often underappreciated role in influencing key aspects of gene transfection. In our efforts to improve gene transfection and understand structure-activity relationships, we synthesized a series of cationic polymers bearing a common poly(carbonate) backbone, and with side chains containing various hydrophobic spacers (propyl, hexyl, 4-methyl benzyl or nonyl) before the cationic moiety. A moderate degree of hydrophobicity was optimal as the cationic poly(carbonate) with hexyl side chains mediated high gene transfection efficiencies while causing low cytotoxicities. (111 words
A Characterization of Different Spark Regimes for Ignition Delay Comparison with Conventional Spark Plugs
poster abstractThe introduction of plasma into combustion and ignition processes has continuously proved to be advantageous when compared to the conventional spark ignition in a wide range of categories. From the capability to ignite leaner mixtures and improve fuel economy to an effective reduction of hazardous emissions and ignition delay, the benefits of integrating non-equilibrium plasma can be utilized for numerous applications including hot jet ignition. Detailed design specifications for the electrode configuration, circuit schematic, and combustion rig are developed and presented. Using a CCD camera and high performance oscilloscope, this paper aims to identify, characterize, and compare the different effects of frequency and pulse width of a driver circuit on the plasma sparks quantitatively in terms of the current, voltage, and energy attributes. Four different plasma regimes are investigated with frequencies ranging from 5.44 Hz to 95.46 kHz and pulse energies ranging from 168 μJ to 14.42 J. The maximum voltage and current characteristics of the plasmas indicate a glow discharge referencing previous experiments. Future work is laid out for a comparison of the ignition progression between a non-thermal plasma system and a traditional spark with using Schlieren imaging
Habitat corridors facilitate genetic resilience irrespective of species dispersal abilities or population sizes
Corridors are frequently proposed to connect patches of habitat that have become isolated due to human‐mediated alterations to the landscape. While it is understood that corridors can facilitate dispersal between patches, it remains unknown whether corridors can mitigate the negative genetic effects for entire communities modified by habitat fragmentation. These negative genetic effects, which include reduced genetic diversity, limit the potential for populations to respond to selective agents such as disease epidemics and global climate change. We provide clear evidence from a forward‐time, agent‐based model (ABM) that corridors can facilitate genetic resilience in fragmented habitats across a broad range of species dispersal abilities and population sizes. Our results demonstrate that even modest increases in corridor width decreased the genetic differentiation between patches and increased the genetic diversity and effective population size within patches. Furthermore, we document a trade‐off between corridor quality and corridor design whereby populations connected by high‐quality habitat (i.e., low corridor mortality) are more resilient to suboptimal corridor design (e.g., long and narrow corridors). The ABM also revealed that species interactions can play a greater role than corridor design in shaping the genetic responses of populations to corridors. These results demonstrate how corridors can provide long‐term conservation benefits that extend beyond targeted taxa and scale up to entire communities irrespective of species dispersal abilities or population sizes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111750/1/eva12255.pd
Parents\u27 Stigmatizing Beliefs About the HPV Vaccine and Their Association With Information Seeking Behavior and Vaccination Communication Behaviors
Parents\u27 stigmatizing beliefs about the HPV vaccine, such as beliefs that it promotes adolescent sexual activity, constitute a notable barrier to vaccine uptake. The purpose of this study is to describe the associations between parents\u27 stigmatizing beliefs about the HPV vaccine, psychosocial antecedents to vaccination, and parents\u27 intentions to vaccinate their children. Parents of vaccine-eligible children
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Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase.
Obesity-associated insulin resistance plays a central role in type 2 diabetes. As such, tyrosine phosphatases that dephosphorylate the insulin receptor (IR) are potential therapeutic targets. The low-molecular-weight protein tyrosine phosphatase (LMPTP) is a proposed IR phosphatase, yet its role in insulin signaling in vivo has not been defined. Here we show that global and liver-specific LMPTP deletion protects mice from high-fat diet-induced diabetes without affecting body weight. To examine the role of the catalytic activity of LMPTP, we developed a small-molecule inhibitor with a novel uncompetitive mechanism, a unique binding site at the opening of the catalytic pocket, and an exquisite selectivity over other phosphatases. This inhibitor is orally bioavailable, and it increases liver IR phosphorylation in vivo and reverses high-fat diet-induced diabetes. Our findings suggest that LMPTP is a key promoter of insulin resistance and that LMPTP inhibitors would be beneficial for treating type 2 diabetes
Reverberation Mapping Measurements of Black Hole Masses in Six Local Seyfert Galaxies
We present the final results from a high sampling rate, multi-month,
spectrophotometric reverberation mapping campaign undertaken to obtain either
new or improved Hbeta reverberation lag measurements for several relatively
low-luminosity AGNs. We have reliably measured thetime delay between variations
in the continuum and Hbeta emission line in six local Seyfert 1 galaxies. These
measurements are used to calculate the mass of the supermassive black hole at
the center of each of these AGNs. We place our results in context to the most
current calibration of the broad-line region (BLR) R-L relationship, where our
results remove outliers and reduce the scatter at the low-luminosity end of
this relationship. We also present velocity-resolved Hbeta time delay
measurements for our complete sample, though the clearest velocity-resolved
kinematic signatures have already been published.Comment: 52 pages (AASTeX: 29 pages of text, 8 tables, 7 figures), accepted
for publication in the Astrophysical Journa
Human Lipoxygenase Pathway Gene Variation and Association with Markers of Subclinical Atherosclerosis in the Diabetes Heart Study
Aims. Genes of the 5-lipoxygenase pathway are compelling candidates for atherosclerosis. We hypothesize that polymorphisms in ALOX12, ALOX15, ALOX5, and ALOX5AP genes are associated with subclinical atherosclerosis in multiple vascular beds. Methods. Families with two or more siblings with type 2 diabetes and their nondiabetic siblings were studied as part of the Diabetes Heart Study (DHS). European American diabetic (n = 828) and nondiabetic (n = 170) siblings were genotyped for SNPs in the ALOX12, ALOX15, ALOX5, and ALOX5AP genes. Subclinical measures of atherosclerosis (IMT, coronary (CorCP), carotid (CarCP) and aortic (AorCP) calcified plaque) were obtained. Results. Associations were observed between ALOX12 with CorCP, ALOX5 with CorCP, AorCP, and IMT, and ALOX5AP with CorCP and CarCP, independent of known epidemiologic risk factors. Further, lipoxygenase pathway SNPs that were associated with measures of atherosclerosis were associated with markers of inflammation (CRP, ICAM-1) and calcification (MGP).
Conclusions. Polymorphisms within ALOX12, ALOX5, and ALOX5AP are genetically associated with subclinical atherosclerosis and with biomarkers of disease in families with type 2 diabetes. These results suggest that variants in lipoxygenase pathway genes may have pleiotropic effects on multiple components that determine risk of cardiovascular disease
Long-term evolution of antigen repertoires among carried meningococci
Most studies of bacterial pathogen populations have been based on isolates collected from individuals with disease, or their contacts, over short time periods. For commensal organisms that occasionally cause disease, such as Neisseria meningitidis, however, the analysis of isolates from long-term asymptomatic carriage is necessary to elucidate their evolution and population structure. Here, we use mathematical models to analyse the structuring and dynamics of three vaccine-candidate antigens among carried meningococcal isolates collected over nearly 30 years in the Czech Republic. The data indicate that stable combinations of antigenic alleles were maintained over this time period despite evidence for high rates of recombination, consistent with theoretical models in which strong immune selection can maintain non-overlapping combinations of antigenic determinants in the presence of recombination. We contrast this antigenic structure with the overlapping but relatively stable combinations of the housekeeping genes observed among the same isolates, and use a novel network approach to visualize these relationships
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