Letter from Henry S. Thompson.

Letter concerning position as instructor of modern languages in the Utah Agricultural College

Can Common Crawl Reliably Track Persistent Identifier (PID) Use Over Time

We report here on the results of two studies using two and four monthly web crawls respectively from the Common Crawl (CC) initiative between 2014 and 2017, whose initial goal was to provide empirical evidence for the changing patterns of use of so-called persistent identifiers. This paper focusses on the tooling needed for dealing with CC data, and the problems we found with it. The first study is based on over $10^{12}$ URIs from over $5 * 10^9$ pages crawled in April 2014 and April 2017, the second study adds a further $3 * 10^9$ pages from the April 2015 and April 2016 crawls. We conclude with suggestions on specific actions needed to enable studies based on CC to give reliable longitudinal information.Comment: 7 pages, 1 figure, submitted to TempWeb201

ECONOMIC SURPLUS AND THE DISTRIBUTIONAL CONSEQUENCES OF DEREGULATING TOBACCO PRODUCTION

Reservations on technical and theoretical grounds in the use of the consumer surplus approach to measure benefits of government programs have often appeared in the literature. Therefore, this paper uses an alternative approach in a case study to estimate the annual economic surplus created in South Carolina from deregulating tobacco production. Impacts of deregulation on cropping patterns and income on representative tobacco farms, and distribution of benefits in the economy are examined. Results of this study indicate that deregulation stimulates the economy and would increase the net value added by $5.8 million in the long run.Agricultural and Food Policy,

An Analysis of Infectious Failures in Acute Cholangitis

To determine the factors responsible for therapeutic failures in acute cholangitis, a series of 127 patients was analyzed. There were 64 females and 63 males whose mean age was 57.2 years. Ninetyfour (74.0%) of these patients were clinically cured with initial measures, whereas 33 patients (26%) failed initial therapy for an infectious reason. No differences were observed between the two groups in regard to age and gender. However, more patients in the group that failed had a malignant cause for their bile duct obstruction (72.7% vs. 42.6%, p < 0.01) and had a pretreatment positive blood culture (45.5% vs. 13.8%, p < 0.01). Patients who failed had a higher mean total bilirubin level (9.7 mg/dl vs. 5.5 mg/dl, p < 0.005) and more of them had a level greater than 2.2 mg/dl (97% vs. 69.9%, p < 0.001). Also, more bile cultures were initially positive (93.9% vs. 76.6%, p < 0.05) and more organisms were isolated per culture (3.88 vs. 2.86, p < 0.03) in the patients who failed. In addition, more patients failed who had two or more organisms in the bile (33% vs. 8.3%, p < 0.02). Patients in whom Candida, or any panresistant organism was isolated also tended to fail. Multivariant analysis showed that malignancy, bacteremia, bilirubin ≥ 2.2 mg/dl, ≥ 2 organisms in the bile and a panresistant organism were the best predictors of treatment failure with a serum bilirubin level ≥ 2.2 mg/dl being the variable that increases a patient's log-odds ratio of failure the greatest. In conclusion, patients with acute cholangitis who have an increased chance to fail initial therapy can be identified, and treatment altered accordingly

Type I interferon signaling is required for activation of the inflammasome during Francisella infection

Francisella tularensis is a pathogenic bacterium whose virulence is linked to its ability to replicate within the host cell cytosol. Entry into the macrophage cytosol activates a host-protective multimolecular complex called the inflammasome to release the proinflammatory cytokines interleukin (IL)-1β and -18 and trigger caspase-1–dependent cell death. In this study, we show that cytosolic F. tularensis subspecies novicida (F. novicida) induces a type I interferon (IFN) response that is essential for caspase-1 activation, inflammasome-mediated cell death, and release of IL-1β and -18. Extensive type I IFN–dependent cell death resulting in macrophage depletion occurs in vivo during F. novicida infection. Type I IFN is also necessary for inflammasome activation in response to cytosolic Listeria monocytogenes but not vacuole-localized Salmonella enterica serovar Typhimurium or extracellular adenosine triphosphate. These results show the specific connection between type I IFN signaling and inflammasome activation, which are two sequential events triggered by the recognition of cytosolic bacteria. To our knowledge, this is the first example of the positive regulation of inflammasome activation. This connection underscores the importance of the cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses

A Hydrogen Bond in Loop A Is Critical for the Binding and Function of the 5-HT3 Receptor†

The binding sites of Cys-loop receptors are formed from at least six loops (A−F). Here we have used mutagenesis, radioligand binding, voltage clamp electrophysiology, and homology modeling to probe the role of two residues in loop A of the 5-HT_3 receptor: Asn128 and Glu129. The data show that substitution of Asn128, with a range of alternative natural and unnatural amino acids, changed the EC_(50) (from ∼10-fold more potent to ∼10-fold less potent than that of the wild type), increased the maximal peak current for mCPBG compared to 5-HT (R_(max)) 2−19-fold, and decreased n_H, indicating this residue is involved in receptor gating; we propose Asn128 faces away from the binding pocket and plays a role in facilitating transitions between conformational states. Substitutions of Glu129 resulted in functional receptors only when the residue could accept a hydrogen bond, but with both these and other substitutions, no [^3H]granisetron binding could be detected, indicating a role in ligand binding. We propose that Glu129 faces into the binding pocket, where, through its ability to hydrogen bond, it plays a critical role in ligand binding. Thus, the data support a modified model of the 5-HT_3 receptor binding site and show that loop A plays a critical role in both the ligand binding and function of this receptor

Instructions for creating camera-ready versions of accepted papers for the Proceedings of HLTD 2011

Abstract This document contains the instructions for preparing a camera-ready manuscript for the proceedings of HLTD 2011.The document itself conforms to its own specifications, and is therefore an example of what your manuscript should look like. These instructions should be used for final versions of accepted papers. Authors are asked to conform to all the directions reported in this document. Credits This document has been adapted from the instructions for ACL-2010 proceedings drafted by Jing-Shin Chang and Regina Barzilay. Instructions for those proceedings were in turn based on the formats of earlier ACL and EACL Conference proceedings. Those versions were written by several persons, includin

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals.

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme