433 research outputs found
A Dual Read-Out Assay to Evaluate the Potency of Compounds Active against Mycobacterium tuberculosis
No full textPMCID: PMC3617142This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Estimation of interdomain flexibility of N-terminus of factor H using residual dipolar couplings
No full textCharacterization of segmental flexibility is needed to understand the biological mechanisms of the very large category of functionally diverse proteins, exemplified by the regulators of complement activation, that consist of numerous compact modules or domains linked by short, potentially flexible, sequences of amino acid residues. The use of NMR-derived residual dipolar couplings (RDCs), in magnetically aligned media, to evaluate interdomain motion is established but only for two-domain proteins. We focused on the three N-terminal domains (called CCPs or SCRs) of the important complement regulator, human factor H (i.e., FH1-3). These domains cooperate to facilitate cleavage of the key complement activation-specific protein fragment, C3b, forming iC3b that no longer participates in the complement cascade. We refined a three-dimensional solution structure of recombinant FH1-3 based on nuclear Overhauser effects and RDCs. We then employed a rudimentary series of RDC data sets, collected in media containing magnetically aligned bicelles (disklike particles formed from phospholipids) under three different conditions, to estimate interdomain motions. This circumvents a requirement of previous approaches for technically difficult collection of five independent RDC data sets. More than 80% of conformers of this predominantly extended three-domain molecule exhibit flexions of <40°. Such segmental flexibility (together with the local dynamics of the hypervariable loop within domain 3) could facilitate recognition of C3b via initial anchoring and eventual reorganization of modules to the conformation captured in the previously solved crystal structure of a C3b:FH1-4 complex.</p
ChemInform Abstract: Utilization of the Suzuki Coupling to Enhance the Antituberculosis Activity of Aryloxazoles.
No full textMycobacterial counts in the lungs and spleens of <i>M. tuberculosis</i>-infected Balb/c mice after treatment with ND-09759 or combination regimens.
No full text<p>Balb/c mice (n = 5) were infected with <i>M. tuberculosis</i> H37Rv by aerosol challenge and then treated by oral gavage with 80% aqueous propylene glycol (solid cycle, vehicle control), ND-09759 (cycle), ND-09759 plus INH (solid square), ND-09759 plus RMP (solid triangle), INH (square) and RMP (triangle), respectively, as described in <i>Materials and Methods</i>. The results show the log<sub>10</sub> CFU in the lung (A and C) and spleen (B and D). C and D, Mycobacterial counts after the completion of chemotherapy and each open cycle represents an individual mouse. ***, p<0.05 compared to no treatment group; **, P<0.05 between ND-09759 alone and ND-09759+ INH or RMP.</p
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Of dragons, palaces, and gods : a mormon perspective on C. S. Lewis
No full textDuring his lifetime C. S. Lewis chose to speak to Christians in plain and simple language that they could understand. Lewis taught and defended truths that he felt were discernible through reason. Morality, free will, and the divinity of Jesus Christ were fundamental to his core beliefs and teachings. His writings have attracted Christian readers from many denominations, including those of the Church of Jesus Christ of Latter-day Saints.
Through references to Lewis by LDS Church leaders and authors, Mormons have been attracted to Lewis's writings in significant ways. General Authorities have used his thoughts and analogies to illustrate certain gospel principles. Many Latter-day Saints have been impressed by the similarities they perceive between Lewis's theology and Mormonism. Such appreciation has led to Lewis's becoming one of the most quoted non-LDS authors in General Conference talks and various Mormon publications.
While Lewis was aware of the Latter-day Saint religion, he chose to worship in the Church of England. Through his writings, however, he entered into a much broader fellowship with millions of Christians around the world. His thoughts on "mere Christianity" have created an enormous common ground on which many have stood. Among those who have set foot upon that soil are the Latter-day Saints.
Given their open-minded approach to theological reflection, Mormons not only read authors like Lewis but also feel comfortable citing his views on human nature and
Christian discipleship. Although they do not agree with everything he says, Mormons treasure particular Lewisian teachings that have a familiar ring of truth to them. Something deep inside them (which they call the Holy Ghost) resonates when they read certain passages of Lewis's writings.
This thesis describes Lewis's theology, the Mormons' discovery of Lewis, and the spread of his reputation among the LDS membership. Lewis has become a popular author in the LDS community largely through numerous references to his writings in General Conference talks and books by leaders like Elder Neal A. Maxwell. While Mormons do not look to Lewis as an authority on doctrinal matters, many acknowledge his valuable insights on how to be better Christians. His ideas challenge and enliven their understanding of Mormon doctrines. They admire Lewis's courage for being a public intellectual who believed in God and for articulating both the stabs of joy and the adversities that he experienced. His words comfort those in the process of being undragoned by Aslan, reminding them that somehow even children can become kings and queens in Narnia
Screening of LOPAC®1280 drug library to identify inhibitors of oxidative phosphorylation in mycobacterium bovis
No full textThe major challenge of tuberculosis control lies in the increased prevalence of emerging drug resistance strains and the ability of mycobacteria to persist under intense environmental stress. Therefore, there is an urgent need for the discovery of compounds with novel actions against the heterogeneous population of mycobacteria. The oxidative phosphorylation pathway has been identified as a promising target due to its essentially for survival in both dormant and replicative mycobacteria. Compound21, which is an experimental drug synthesized by Garrett C. Moraski from Montana State University, was found to be such a drug which inhibits the cytochrome bd oxidase. Based on the characteristics of the drug, compound21 was found to deplete intracellular ATP content of nutrient-starved mycobacteria in the presence of Q203. However, despite the ability to enhance the potency of Q203 action in replicative mycobacteria, the compound showed no activity on growth inhibition alone. In this study, the potency of Q203 was validated to be shifted from bacteriostatic to bactericidal upon the genetic deletion of the cytochrome bd oxidase. Four pharmacologically active drug compounds were also identified from the screening of the LOPAC®1280 library as potential cytochrome bd inhibitor which displayed similar action as compound21 with Q203.Bachelor of Science in Biological Science
EXPERIENCE REINFORCES VIEWS ON CAPITAL PUNISHMENT
No full textMichael C. Garrett\u27s (J.D.\u2773) 24 years of defense experience in capital murder cases confirms his belief that capital punishment is wrong. To read the complete story, see The Augusta Chronicle (registration required.) In the search field, enter the article title Lawyer keeps zeal for job. The article was published 12/6/04, and the author is Sandy Hodson
EXPERIENCE REINFORCES VIEWS ON CAPITAL PUNISHMENT
No full textMichael C. Garrett\u27s (J.D.\u2773) 24 years of defense experience in capital murder cases confirms his belief that capital punishment is wrong. To read the complete story, see The Augusta Chronicle (registration required.) In the search field, enter the article title Lawyer keeps zeal for job. The article was published 12/6/04, and the author is Sandy Hodson
A comparison of five different bone resorption markers in osteosarcoma‐bearing dogs, normal dogs, and dogs with orthopedic diseases
No full textBackground: Various bone resorption markers in humans are useful for supporting the diagnosis of malignant skeletal
pathology, with certain bone resorption markers appearing to be more discriminatory for detecting cancer-induced osteolysis
than others. Canine osteosarcoma (OSA) is characterized by focal bone destruction, but a systematic investigation for determining which bone resorption marker best supports the diagnosis of OSA in dogs has not been reported.
Hypothesis: Dogs with OSA will have increased concentrations of bone resorption markers compared with healthy dogs
and dogs with orthopedic disorders. Differences will exist among various bone resorption markers for their ability to support
the diagnosis of malignant osteolysis in dogs with OSA.
Animals: Single time point, cross-sectional, cohort study including dogs with OSA (n 5 20) or orthopedic disorders (n 5 20)
and healthy dogs (n 5 22).
Methods: Basal concentrations of urine and serum N-telopeptide (NTx), urine and serum C-telopeptide (CTx), and urine
deoxypyridinoline (DPD) were compared among all 3 groups.
Results: Compared with healthy dogs and dogs with orthopedic disorders, urine NTx, serum NTx, and serum CTx concentrations were significantly increased in dogs with OSA. For urine NTx and serum NTx, the calculated lower and upper 95%
confidence limits in dogs with OSA did not overlap with dogs diagnosed with orthopedic disorders or healthy dogs.
Conclusions and clinical importance: Of the markers evaluated in this study, urine NTx and serum NTx appear to be the
most discriminatory resorption markers supporting the diagnosis of focal malignant osteolysis in dogs with OSA.
Key words: Bone pain; Canine cancer; Circulating surrogate markers; Focal malignant osteolysis
Thermodynamic improvements for the space thermoacoustic refrigerator (STAR)
No full textThe objective of the STAR project is to test and space qualify a new continuous cycle cryogenic refrigeration system for cooling of sensors and electronics which is based upon the newly discovered thermoacoustic heat pumping effect. The new refrigerator has no sliding seals, a cycle frequency of about 300 Hz, and uses acoustic resonance to enhance the overall power density and efficiency. This thesis is concerned specifically with the design and testing of the thermodynamic element (or stack), which is responsible for the thermo- acoustic power conversion, and the testing of binary inert gas mixtures as working fluids. Using the refrigerator's coefficient of performance relative to the ideal Carnot coefficient of performance as a measure of efficiency, we have achieved a 93% improvement over previous designs. Keywords: Thermoacoustic refrigerator, ThesesU.S. Navy (U.S.N.) author.;c.1, c.2http://archive.org/details/thermodynamicimp109452313
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