454 research outputs found

    Using Google Analytics, Voyant and Other Tools to Better Understand Use of Manuscript Collections at L. Tom Perry Special Collections

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    [Excerpt] Developing strategies for making data-driven, objective decisions for digitization and value-added processing. based on patron usage has been an important effort in the L. Tom Perry Special Collections (hereafter Perry Special Collections). In a previous study, the authors looked at how creating a matrix using both Web analytics and in-house use statistics could provide a solid basis for making decisions about which collections to digitize as well as which collections merited deeper description. Along with providing this basis for decision making, the study also revealed some intriguing insights into how our collections were being used and raised some important questions about the impact of description on both digital and physical usage. We have continued analyzing the data from our first study and that data forms the basis of the current study. It is helpful to review the major outcomes of our previous study before looking at what we have learned in this deeper analysis. In the first study, we utilized three sources of statistical data to compare two distinct data points (in-house use and online finding aid use) and determine if there were any patterns or other information that would help curators in the department make better decisions about the items or collections selected for digitization or value-added processing. To obtain our data points, we combined two data sources related to the in-person use of manuscript collections in the Perry Special Collections reading room and one related to the use of finding aids for manuscript collections made available online through the department’s Finding Aid database ( http://findingaid.lib.byu.edu/). We mapped the resulting data points into a four quadrant graph (see figure 1)

    The Development and Professionalization of the Utah State Archives, 1897-1968

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    The 20th century saw the rise and development of the archival profession. This paper examines what it means to be a profession and how the characteristics of a profession began to manifest themselves in the archival community using the Utah State Archives as a case study. The Utah State Archives reflects many of the national trends towards professionalization as it was initially part of the Utah State Historical Society and eventually became its own entity

    Identification and Characterization of a Nontypeable Haemophilus Influenzae Putative Toxin-Antitoxin Locus

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    Background: Certain strains of an obligate parasite of the human upper respiratory tract, nontypeable Haemophilus influenzae (NTHi), can cause invasive diseases such as septicemia and meningitis, as well as chronic mucosal infections such as otitis media. To do this, the organism must invade and survive within both epithelial and endothelial cells. We have identified a facilitator of NT(Hi) survival inside human cells, virulence-associated protein D (vapDHi, encoded by gene H10450). Both vapDHi and a flanking gene, H10451, exhibit the genetic and physical characteristics of a toxin/antitoxin ( TA) locus, with VapDHi serving as the toxin moiety and H10451 as the antitoxin. We propose the name VapXHi for the H10451 antitoxin protein. Originally identified on plasmids, TA loci have been found on the chromosomes of a number of bacterial pathogens, and have been implicated in the control of translation during stressful conditions. Translation arrest would enhance survival within human cells and facilitate persistent or chronic mucosal infections. Results: Isogenic mutants in vapDHi were attenuated for survival inside human respiratory epithelial cells (NCI-H292) and human brain microvascular endothelial cells (HBMEC), the in vitro models of mucosal infection and the blood-brain barrier, respectively. Transcomplementation with a vapDHi allele restored wild-type NTHi survival within both cell lines. A PCR survey of 59 H. influenzae strains isolated from various anatomical sites determined the presence of a vapDHi allele in 100% of strains. Two isoforms of the gene were identified in this population; one that was 91 residues in length, and another that was truncated to 45 amino acids due to an in-frame deletion. The truncated allele failed to transcomplement the NTHi vapDHi survival defect in HBMEC. Subunits of full-length VapDHi homodimerized, but subunits of the truncated protein did not. However, truncated protein subunits did interact with full-length subunits, and this interaction resulted in a dominant-negative phenotype. Although Escherichia coli does not contain a homologue of either vapDHi or vapXHi, overexpression of the VapDHi toxin in trans resulted in E. coli cell growth arrest. This arrest could be rescued by providing the VapXHi antitoxin on a compatible plasmid. Conclusion: We conclude that vapDHi and vapXHi may constitute a H. influenzae TA locus that functions to enhance NTHi survival within human epithelial and endothelial cells

    Exploring the American Archivist: Corpus analysis tools and the professional literature

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    The literature of a professional community provides insights into what members of that community value and underscores key professional issues. Periodic analyses of professional literature are an important way for these communities to identify trends that deserve further exploration. This article introduces the use of corpus analysis tools such as Voyant Tools and discusses their value in performing periodic analyses of professional literature. As an example, it presents a limited study examining the use of the term “theory” in the American Archivist

    Crystal Structure of VapBC-1 from Nontypeable \u3ci\u3eHaemophilus influenzae\u3c/i\u3e and the Effect of Pin Domain Mutations on Survival During Infection

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    Toxin-antitoxin (TA) gene pairs have been identified in nearly all bacterial genomes sequenced to date and are thought to facilitate persistence and antibiotic tolerance. TA loci are classified into various types based upon the characteristics of their antitoxins, with those in type II expressing proteic antitoxins. Many toxins from type II modules are ribonucleases that maintain a PilT N-terminal (PIN) domain containing conserved amino acids considered essential for activity. The vapBC (virulence-associated protein) TA system is the largest subfamily in this class and has been linked to pathogenesis of nontypeable Haemophilus influenzae (NTHi). In this study, the crystal structure of the VapBC-1 complex from NTHi was determined to 2.20 Å resolution. Based on this structure, aspartate-to-asparagine and glutamate-to-glutamine mutations of four conserved residues in the PIN domain of the VapC-1 toxin were constructed and the effects of the mutations on protein-protein interactions, growth of Escherichia coli, and pathogenesis ex vivo were tested. Finally, a novel model system was designed and utilized that consists of an NTHi ΔvapBC-1 strain complemented in cis with the TA module containing a mutated or wild-type toxin at an ectopic site on the chromosome. This enabled the analysis of the effect of PIN domain toxin mutants in tandem with their wild-type antitoxin under the control of the vapBC-1 native promoter and in single copy. This is the first report of a system facilitating the study of TA mutant operons in the background of NTHi during infections of primary human tissues ex vivo

    Better Living Through Chemistry: Addressing Emerging Antibiotic Resistance

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    The increasing emergence of multidrug-resistant bacteria is recognized as a major threat to human health worldwide. While the use of small molecule antibiotics has enabled many modern medical advances, it has also facilitated the development of resistant organisms. This minireview provides an overview of current small molecule drugs approved by the US Food and Drug Administration (FDA) for use in humans, the unintended consequences of antibiotic use, and the mechanisms that underlie the development of drug resistance. Promising new approaches and strategies to counter antibiotic-resistant bacteria with small molecules are highlighted. However, continued public investment in this area is critical to maintain an edge in our evolutionary arms race against antibiotic-resistant microorganisms. Impact statement The alarming increase in antibiotic-resistant microorganisms is a rapidly emerging threat to human health throughout the world. Historically, small molecule drugs have played a major role in controlling bacterial infections and they continue to offer tremendous potential in countering resistant organisms. This minireview provides a broad overview of the relevant issues, including the diversity of FDA-approved small molecule drugs and mechanisms of drug resistance, unintended consequences of antibiotic use, the current state of development for small molecule antibacterials and financial challenges that impact progress towards novel therapies. The content will be informative to diverse stakeholders, including clinicians, basic scientists, translational scientists and policy makers, and may be used as a bridge between these key players to advance the development of much-needed therapeutics

    Regulation of the vapBC-1 Toxin-Antitoxin Locus in Nontypeable Haemophilus influenzae

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    Nontypeable Haemophilus influenzae (NTHi) are human-adapted commensal bacteria that can cause a number of chronic mucosal infections, including otitis media and bronchitis. One way for these organisms to survive antibiotic therapy and cause recurrent disease is to stop replicating, as most antimicrobials target essential biosynthetic pathways. Toxin-antitoxin (TA) gene pairs have been shown to facilitate entry into a reversible bacteriostatic state. Characteristically, these operons encode a protein toxin and an antitoxin that associate following translation to form a nontoxic complex, which then binds to and regulates the cognate TA promoter. Under stressful conditions, the labile antitoxin is degraded and the complex disintegrates, freeing the stable toxin to facilitate growth arrest. How these events affected the regulation of the TA locus, as well as how the transcription of the operon was subsequently returned to its normal state upon resumption of growth, was not fully understood. Here we show that expression of the NTHi vapBC-1 TA locus is repressed by a complex of VapB-1 and VapC-1 under conditions favorable for growth, and activated by the global transactivator Factor for Inversion Stimulation (Fis) upon nutrient upshift from stationary phase. Further, we demonstrate for the first time that the VapC-1 toxin alone can bind to its cognate TA locus control region and that the presence of VapB-1 directs the binding of the VapBC-1 complex in the transcriptional regulation of vapBC-1

    Formation of Low Mass Stars in Elliptical Galaxy Cooling Flows

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    X-ray emission from hot (T = 10^7 K) interstellar gas in massive elliptical galaxies indicates that 10^{10} M_sun has cooled over a Hubble time, but optical and radio evidence for this cold gas is lacking. We provide detailed theoretical support for the hypothesis that this gas has formed into low luminosity stars. Within several kpc of the galactic center, interstellar gas first cools to T = 10^4 K where it is heated by stellar UV and emits the observed diffuse optical line emission. This cooling occurs at a large number (10^6) of isolated sites. After less than a solar mass of gas has accumulated (10^{-6} M_sun/yr) at a typical cooling site, a neutral (HI or H_2) core develops in the HII cloud where gas temperatures drop to T = 15 K and the ionization level (from thermal X-rays) is very low (x = 10^{-6}). We show that the maximum mass of cores that become gravitationally unstable is only about 2 M_sun. No star can exceed this mass. Fragmentation of collapsing cores produces a population of low mass stars with a bottom-heavy IMF and radial orbits. Gravitational collapse and ambipolar diffusion are rapid. The total mass of star-forming (dust-free) HI or H_2 cores in a typical bright elliptical is only 10^6 M_sun, below current observational thresholds.Comment: 23 pages in AASTEX LaTeX with 8 figures; accepted by Astrophysical Journa
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