Probability Density Functions of Observed Rainfall in Montana

The question of whether a rain rate probability density function (PDF) can vary uniformly between precipitation events is examined. Image analysis on large samples of radar echoes is possible because of advances in technology. The data provided by such an analysis easily allow development of radar reflectivity factors (and by extension rain rate) distribution. Finding a PDF becomes a matter of finding a function that describes the curve approximating the resulting distributions. Ideally, one PDF would exist for all cases; or many PDF's that have the same functional form with only systematic variations in parameters (such as size or shape) exist. Satisfying either of theses cases will, validate the theoretical basis of the Area Time Integral (ATI). Using the method of moments and Elderton's curve selection criteria, the Pearson Type 1 equation was identified as a potential fit for 89 percent of the observed distributions. Further analysis indicates that the Type 1 curve does approximate the shape of the distributions but quantitatively does not produce a great fit. Using the method of moments and Elderton's curve selection criteria, the Pearson Type 1 equation was identified as a potential fit for 89% of the observed distributions. Further analysis indicates that the Type 1 curve does approximate the shape of the distributions but quantitatively does not produce a great fit

Eliminating the Abattoir Pen Lairages to Decrease the Prevalence of Salmonella in Cull Sows

The study objective, to determine the role of abattoir antemortem pens in preharvest Salmonella enterica contamination, was conducted over 4 sampling periods, February-April 2002. A total of 40 sows were selected for each period at the same collection point and transported to the abattoir. Twenty (20) were unloaded and sent directly to harvest and 20 held in antemortem pen for 2 h before harvest. Samples collected included ileocecal and subiliac lymph nodes, cecal and transverse colon contents, pre-rinse carcass sponge swabs for the right and left carcass sections and chopped meat blocks composited from these carcasses. The percentage of positive samples (all tissues) and cecal content from sows held in the antemortem pens (59%, 55 %, respectively) were significantly higher (P \u3c 0.05) compared to direct delivered (44%, 39 % respectively). This study demonstrates that normal antemortem holding practices contributed to increased Salmonella enterica contamination of the digestive tract

Conformational ensembles of RNA oligonucleotides from integrating NMR and molecular simulations

RNA molecules are key players in numerous cellular processes and are characterized by a complex relationship between structure, dynamics, and function. Despite their apparent simplicity, RNA oligonucleotides are very flexible molecules, and understanding their internal dynamics is particularly challenging using experimental data alone. We show how to reconstruct the conformational ensemble of four RNA tetranucleotides by combining atomistic molecular dynamics simulationswith nuclear magnetic resonance spectroscopy data. The goal is achieved by reweighting simulations using a maximum entropy/Bayesian approach. In this way, we overcome problems of current simulation methods, as well as in interpreting ensemble- and time-averaged experimental data. We determine the populations of different conformational states by considering several nuclear magnetic resonance parameters and point toward properties that are not captured by state-of-the-art molecular force fields. Although our approach is applied on a set of model systems, it is fully general and may be used to study the conformational dynamics of flexible biomolecules and to detect inaccuracies in molecular dynamics force fields

Peracute Infection of Swine With Salmonella

It has recently been experimentally demonstrated that pigs exposed naturally to Salmonella on the floor of abattoir holding pens can become infected between two and six hours after being placed in the pens. In addition we have demonstrated that tonsillar tissue are almost immediately culture positive following such exposure under experimental conditions. The objective of this study was to determine the shortest amount of time necessary for infection of selected tissues and to determine if the tonsil served as a route for Salmonella entry into lymphoid tissues draining the tonsil. Forty-four Salmonella-negative, market age pigs (90 to 110 kg) were fasted overnight and exposed to approximately 2 X 106 Salmonella enterica serotype Typhimurium strain X4232 (nalidixic acid resistant). The bacteria were mixed with a fecal slurry and the slurry spread on the floor of the pens. Pigs were euthanized at 15, 30, 45, 60 and 120 minutes following initial exposure. Tonsil of the soft palate, medial retropharyngeal lymph node, ileocecal lymph node, a five centimeter section of the terminal ileum, cecal contents and 100 ml of blood were cultured for Salmonella. Strain X4232 was isolated from 98 % (43/44) of tonsils. Strain X4232 was isolated from the ileocecal lymph node within 45 minutes (2/9 pigs), terminal ileum within 15 minutes (1/9 pigs), cecal contents within 15 minutes (1/9 pigs), and blood within 45 minutes (1/9 pigs). Strain X4232 was not recovered from the medial retropharyngeal lymph node, indicating that the organism did not move rapidly into this node from the tonsil of the soft palate. Results of this study indicate that Salmonella can be recovered from selected tissues in market age swine in less than the normal two hour abattoir holding time

Bats of St. Vincent, Lesser Antilles

The chiropteran fauna of the island of Saint Vincent, represented by 12 species, is among the most complex in the Lesser Antilles, being represented by four families including Noctilionidae (1 species), Mormoopidae (1), Phyllostomidae (8), and Molossidae (2). This fauna includes four trophic guilds as represented by Noctilio leporinus (piscivore/insectivore); Glossophaga longirostris and Monophyllus plethodon (nectarivore/pollenivore); Artibeus lituratus, A. schwartzi, Brachyphylla cavernarum, Ardops nichollsi, and Sturnira paulsoni (frugivore); and Pteronotus fuscus, Micronycteris buriri, Molossus molossus, and Tadarida brasiliensis (insectivore). One species—Micronycteris buriri—and two subspecies—Sturnira paulsoni paulsoni and Ardops nichollsi vincentensis—are endemic to the island. Recent advancements in population genomics have led to the discovery of the reticulated evolutionary history of Artibeus schwartzi and it is likely that the formation of the hybrid evolutionary trajectory of this species is linked with classical island biogeography. The bat fauna of St. Vincent is unique in the West Indies, characterized by being a crossroads for species, an outpost for both northern and southern species, the boundary for a multi-island bat fauna as marked by Koopman’s Line, and a site of endemism. Based on our studies, we place the bat fauna of St. Vincent as the southern-most island in the Lesser Antillean Faunal Core

Synthesis of deuterium‐labelled amlexanox and its metabolic stability against mouse, rat, and human microsomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149374/1/jlcr3716_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149374/2/jlcr3716.pd

A chimeric virus-mouse model system for evaluating the function and inhibition of papain-like proteases of emerging coronaviruses

To combat emerging coronaviruses, developing safe and efficient platforms to evaluate viral protease activities and the efficacy of protease inhibitors is a high priority. Here, we exploit a biosafety level 2 (BSL-2) chimeric Sindbis virus system to evaluate protease activities and the efficacy of inhibitors directed against the papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus (SARS-CoV), a biosafety level 3 (BSL-3) pathogen. We engineered Sindbis virus to coexpress PLpro and a substrate, murine interferon-stimulated gene 15 (ISG15), and found that PLpro mediates removal of ISG15 (deISGylation) from cellular proteins. Mutation of the catalytic cysteine residue of PLpro or addition of a PLpro inhibitor blocked deISGylation in virus-infected cells. Thus, deISGylation is a marker of PLpro activity. Infection of alpha/beta interferon receptor knockout (IFNAR−/−) mice with these chimeric viruses revealed that PLpro deISGylation activity removed ISG15-mediated protection during viral infection. Importantly, administration of a PLpro inhibitor protected these mice from lethal infection, demonstrating the efficacy of a coronavirus protease inhibitor in a mouse model. However, this PLpro inhibitor was not sufficient to protect the mice from lethal infection with SARS-CoV MA15, suggesting that further optimization of the delivery and stability of PLpro inhibitors is needed. We extended the chimeric-virus platform to evaluate the papain-like protease/deISGylating activity of Middle East respiratory syndrome coronavirus (MERS-CoV) to provide a small-animal model to evaluate PLpro inhibitors of this recently emerged pathogen. This platform has the potential to be universally adaptable to other viral and cellular enzymes that have deISGylating activities

Electrical and structural properties of In-implanted Si1−xGex alloys

We report on the effects of dopant concentration and substrate stoichiometry on the electrical and structural properties of In-implanted Si1−xGex alloys. Correlating the fraction of electrically active In atoms from Hall Effect measurements with the In atomic environment determined by X-ray absorption spectroscopy, we observed the transition from electrically active, substitutional In at low In concentration to electrically inactive metallic In at high In concentration. The In solid-solubility limit has been quantified and was dependent on the Si1−xGex alloy stoichiometry; the solid-solubility limit increased as the Ge fraction increased. This result was consistent with density functional theory calculations of two In atoms in a Si1−xGex supercell that demonstrated that In–In pairing was energetically favorable for x ≲ 0.7 and energetically unfavorable for x ≳ 0.7. Transmission electron microscopy imaging further complemented the results described earlier with the In concentration and Si1−xGex alloy stoichiometry dependencies readily visible. We have demonstrated that low resistivity values can be achieved with In implantation in Si1−xGex alloys, and this combination of dopant and substrate represents an effective doping protocol

Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy

Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore the structural determinants of ALDH1A isoform selectivity in a series of small-molecule inhibitors in support of research into the role of ALDH1A in cancer stem cells. An SAR campaign guided by a cocrystal structure of the HTS hit CM39 (7) with ALDH1A1 afforded first-in-class inhibitors of the ALDH1A subfamily with excellent selectivity over the homologous ALDH2 isoform. We also discovered the first reported modestly selective single isoform 1A2 and 1A3 inhibitors. Two compounds, 13g and 13h, depleted the CD133+ putative cancer stem cell pool, synergized with cisplatin, and achieved efficacious concentrations in vivo following IP administration. Compound 13h additionally synergized with cisplatin in a patient-derived ovarian cancer spheroid model

On Linear Information Systems

Scott's information systems provide a categorically equivalent, intensional description of Scott domains and continuous functions. Following a well established pattern in denotational semantics, we define a linear version of information systems, providing a model of intuitionistic linear logic (a new-Seely category), with a "set-theoretic" interpretation of exponentials that recovers Scott continuous functions via the co-Kleisli construction. From a domain theoretic point of view, linear information systems are equivalent to prime algebraic Scott domains, which in turn generalize prime algebraic lattices, already known to provide a model of classical linear logic