1,906 research outputs found
The Problem of black access to American higher education is connected to institutional underpreparation
Illumination of the Golgi apparatus of Pathogenic and Nonpathogenic Naegleria species
In this study, Naegleria fowleri, a pathogenic amoeba and the causative agent of Primary Amebic Meningoencephalitis (PAM), was utilized to determine the presence or absence of classically conserved Golgi molecules featured in the expression of a Golgi apparatus. Previous studies concluded no Golgi expression via light microscopy and transmission electron microscopy, but a recent report on Naegleria gruberi indicated the presence of dispersed Golgi tubules. Non-pathogenic species of the Naegleria genus such as Naegleria gruberi 30540 and Naegleria lovaniensis 30569 were utilized in Western immunoblot analysis compared to reduced whole-cell lysate proteins of two strains of N. fowleri and Vero CCL-81, Chlorocebus sp. kidney epithelial cells, which were utilized as a positive control for Golgi expression. N. fowleri and N. lovaniensis whole-cell lysates had indications of a 110 kDa reduced protein, associated with the predicted molecular weights of the beta-COPI subunit of the COPI cis-Golgi vesicular transport complex with further Western immunoblot indication of a weak band around 25 kDa corresponding to rabbit polyclonal antibodies specific for ARF1. Serial Dilutions of Wheat Germ Agglutinin Alexa Fluor 488TM were performed on Vero cells, Naegleria fowleri 30894, and N. gruberi 30540 with 1:100 dilution of recommended stock dilution of WGA 488 determined for utilization in sequential immunofluorescence. Sequential immunofluorescence with Wheat Germ Agglutinin Alexa Fluor 488TM and then blocked with 3% BSA:PBS [wt/vol] dilution with subsequent incubation in rabbit anti-beta-COPI primary 1:250, and 1:1000 of Alexa Fluor 594 goat anti-rabbit secondary antibody exposure showed strong indications of organized cis- and trans-punctate Golgi body markers in close association in individual and dividing cells of Naegleria fowleri and conserved Golgi expression in the positive control Vero cells, but further experiments are necessary to verify this finding with N. fowleri
Advanced Conducting Project
Adoramus Te by Giovanni Pierluigi da Palestrina; edited by Brian Marble -- Plaudant Aetheri by Ignaz Holzbauer; edited by Martin Banner -- Kyrie (from Mass No. 6 in E-flat Major ) by Franz Schubert -- Cantique de Jean Racine by Gabriel Faure; edited by H. Zipper -- The Lamb by John Travener -- Russian Picnic by Harvey Enders -- N\u27kosi Sikelel\u27I Afrika by Enoch Mankayi Sontonga; transcribed, edited and annotated by Nick Page and Joseph Shabalala -- Lua, Lua, Lua by Esther Scliar; edited by Daniel Fufino Afonso, Jr. -- Ching-A-Ring-Chaw by Aaron Copland; arranged by Irving Fine
Synthesis of Subtype Selective Bz/GABAA Receptor Ligands for the Treatment of Anxiety, Epilepsy and Neuropathic Pain, as Well as Schizophrenia and Asthma
The α2/α3 subtype selective Bz/GABAA receptor positive allosteric modulator HZ-166 (3) has been shown to be a nonsedating anxiolytic with anticonvulsant and antihyperalgesic activity. However, instability in vitro and in vivo has hindered its advancement into clinical trials. A series of ligands based off HZ-166 (3) were synthesized. Many of these ligands were designed to increase metabolic stability, while others were synthesized to study the effects that electronics and sterics have on the efficacy exerted when bound to the GABAA receptor. The α3 subtype selective methyl ester MP-III-024 (19) was shown to have increased resistance to metabolism in in vitro liver microsomal studies and exhibited significant anxiolytic and antihyperalgesic effects in mice without showing signs of sedation. However, pharmacokinetic studies indicated that esters as a functional group may not be suitable for extensive preclinical studies.
A series of heterocyclic bioisosteres were synthesized to specifically overcome short half-lives in vivo. The oxadiazole MP-III-080 (34) and oxazole KRM-II-81 (36) underwent pharmacokinetic studies and were both found to exist in plasma and brain samples in high levels. These results indicated that these and related heterocycles would be stable in vivo to undergo extensive preclinical trials. A dozen ligands were assessed in vivo in an anxiolytic marble burying assay and a rotarod assay designed to measure ataxic effects. The results from these studies and other in vitro protocols led to additional studies using KRM-II-81 (36). This oxazole 36 was found to exhibit significant anxiolytic and anticonvulsant properties, including reducing network firing rate frequency in human brain tissue from a patient suffering from resistance epilepsy. In addition, KRM-II-81 (36) was found to be more efficacious than gabapentin to reverse the effects of hyperalgesia in a neuropathic pain model at a lower dose using rats, as well as exhibiting antidepressant-like effects.
The α5 GABAA receptor subtype has been linked to the cognitive disorders in such diseases as schizophrenia, bipolar I disorder and major depressive disorder. The enantiomers SH-053-2\u27F-S-CH3 (51) and SH-053-2\u27F-R-CH3 (52) have been shown to be α2/α3/α5- and α5- subtype selective agonists, respectively. Both ligands (S)-51 and (R)-52 have been shown to reduce some positive symptoms of schizophrenia; the S-enantiomer 51 was active in the poly(I:C) model of schizophrenia while the R-enantiomer 52 was active in the MAM-model of schizophrenia. Due to the high rate of comorbidity of schizophrenia with anxiety, epilepsy and depression, the S-enatiomer (51) is shown here to be useful in these instances exhibiting anxiolytic and anticonvulsant properties. In addition, work on analogs of 52 produced MP-III-004 (63), an α5 subtype selective ligand with reduced efficacy at the α1, α2 and α3 subtypes as compared to 52, as well as the very potent α5 positive allosteric modulator MP-III-022 (65). This methyl amide 65 was shown to activate α5 subtypes in vivo in rats at low concentrations, providing a valuable tool to study the α5 GABAA receptor subtype. Recent work has shown SH-053-2\u27F-R-CH3 (52) and MP-III-022 (65) exert antidepressant-like effects in mice, indicating a new use for α5 subtype selective ligands. Moreover, work by Emala et al. has discovered a use for α5 subtype selective ligands outside of the central nervous system. A number of the ligands, especially the α5 selective acid 73, presented herein have been shown to relax precontracted human and guinea pig airway smooth muscle and may provide a novel treatment for those who suffer from asthma
Completed at Calvary: An Examination of the Extent of the Atonement
Calvinism\u27s limited atonement is the pillar that has been notorious for being the weak link in the Calvinists\u27 theological system (TULIP). This paper purposed to delve into the legitimacy of their argument, using the popular penal theory as the foundation for determining the extent of the atonement. Here Christ\u27s sacrifice is seen as the act accomplishing such things as reconciliation and redemption, instead of merely providing potentials effectual upon faith, for all those to whom the atonement extends. Three problematic texts were examined and dealt with, maintaining consistency theologically. From the basis of the penal view, both universal salvation and particular redemption logically follow, depending on whether Christ died for all or some. Since universalism is not a valid evangelical doctrine it was discarded, leaving particular redemption as the sole conclusion of the penal theory
Voluntary Funding for Generic Advertising Using a Provision Point Mechanism: An Experimental Analysis of Option Assurance
The mandatory nature of generic advertising funding remains a contentious issue. Theoretically and in laboratory environments, a provision point mechanism with a money-back guarantee offers an attractive voluntary alternative to the standard voluntary contribution mechanisms, yet in practice, few examples of multiple-round provision point mechanisms exist. A practical concern with applying these mechanisms is that even a slight shortfall in contributions relative to the designated funding threshold in one period would engender an irreversible shutdown of administrative capacity with negative consequences for subsequent periods. This paper uses experimental economics to test new two-threshold provision point mechanisms in the context of check-off programs for funding commodity marketing programs that would separately fund the minimum administrative capacity and the more costly full marketing program. In these mechanisms, even if a funding shortfall occurs for the full marketing program, the low threshold can maintain the administrative capacity and retain the option for future funding of advertising. We demonstrate that providing such "option assurance" does not lead to a decrease in overall contributions and, in some settings, can increase producer surplus.Marketing,
Potential Terrorist Uses of Highway-Borne Hazardous Materials, MTI Report 09-03
The Department of Homeland Security (DHS) has requested that the Mineta Transportation Institutes National Transportation Security Center of Excellence (MTI NTSCOE) provide any research it has or insights it can provide on the security risks created by the highway transportation of hazardous materials. This request was submitted to MTI/NSTC as a National Transportation Security Center of Excellence. In response, MTI/NTSC reviewed and revised research performed in 2007 and 2008 and assembled a small team of terrorism and emergency-response experts, led by Center Director Brian Michael Jenkins, to report on the risks of terrorists using highway shipments of flammable liquids (e.g., gasoline tankers) to cause casualties anywhere, and ways to reduce those risks. This report has been provided to DHS. The teams first focus was on surface transportation targets, including highway infrastructure, and also public transportation stations. As a full understanding of these materials, and their use against various targets became revealed, the team shifted with urgency to the far more plentiful targets outside of surface transportation where people gather and can be killed or injured. However, the team is concerned to return to the top of the use of these materials against public transit stations and recommends it as a separate subject for urgent research
Thin and lumpy: an experimental investigation of water quality trading
Water quality trading schemes in the United States can predominantly be characterized by low trading volumes. In this paper we utilize laboratory economics experiments to explore the extent to which the technology through which pollution abatement is achieved influences market outcomes. Mirroring the majority of water quality trading markets, the sessions utilize small trading groups composed of six participants. To understand the extent to which abatement technology influences trading behavior, the experimental treatments vary the degree of heterogeneity in initial abatement costs and the potential for long-lived investments in cost-reducing abatement technology.Environmental Economics and Policy,
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