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Search Results: 1 - 10 of 198223 matches for " Clarence N. Ahlem "
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17 -Ethynyl-androst-5-ene-3 ,7 ,17 -triol (HE3286) Is Neuroprotective and Reduces Motor Impairment and Neuroinflammation in a Murine MPTP Model of Parkinson’s Disease
Ferdinando Nicoletti,Ingrid Philippens,Paolo Fagone,Clarence N. Ahlem,Christopher L. Reading,James M. Frincke,Dominick L. Auci
Parkinson's Disease , 2012, DOI: 10.1155/2012/969418
Abstract: 17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) is a synthetic androstenetriol in Phase II clinical development for the treatment of inflammatory diseases. HE3286 was evaluated for blood-brain barrier (BBB) permeability in mice, and efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson’s disease (PD). We found that HE3286 freely penetrated the BBB. HE3286 treatment significantly improved motor function compared to vehicle in the rotarod test (mean 58.2?sec versus 90.9?sec, ), and reduced inflammatory mediator gene expression in the brain (inducible nitric oxide synthase, 20%, ; tumor necrosis factor α, 40%, , and interleukin-1β, 33%, ) measured by reverse-transcriptase polymerase chain reaction. Brain tissue histopathology and immunohistochemistry showed that HE3286 treatment increased the numbers of tyrosine hydroxylase-positive cells by 17% compared to vehicle ( ), and decreased the numbers of damaged neurons by 38% relative to vehicle ( ). L-3,4-dihydroxyphenylalanine (L-DOPA) efficacy was not enhanced by concurrent administration of HE3286. HE3286 administration prior to MPTP did not enhance efficacy. Our data suggest a potential role for HE3286 in PD treatment, and provides incentive for further investigation. 1. Introduction PD is a neurodegenerative disorder characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) and decreased levels of dopamine in the putamen of the dorsolateral striatum. The loss of dopamine in the striatum manifests clinically as motor disabilities that include bradykinesia, resting tremor, and muscular rigidity. Diagnosis is based on motor symptoms, which become evident only after the loss of more than 50% of the SNpc DAergic neurons and 60–80% of striatal dopamine [1]. Prolonged treatment of PD with L-DOPA usually results in a dyskinesia that can be more disabling than the disease itself; therefore, there is a great need for alternative therapeutic modalities. The acute MPTP mouse model of nigrostriatal degeneration recapitulates the DAergic neuron loss seen in PD and currently represents the most commonly used toxin-induced mouse model of PD [2]. MPTP’s mechanism of toxicity is complex, and exerted through its toxic metabolite, methyl-4-phenylpyridinium (MPP+) ion, which is taken up selectively by DAergic neurons through the dopamine transporter. Inside the cell, MPP+ is a mitochondrial toxin, which induces neuronal death through several mechanisms that include oxidative stress [3], excitotoxicity [4], and
17α-Ethynyl-5α-androstane-3α, 17β-diol Treatment of MNU-Induced Mammary Cancer in Rats
Clarence N. Ahlem,James M. Frincke,Steven K. White,Christopher L. Reading,Richard J. Trauger,Rajkumar Lakshmanaswamy
International Journal of Breast Cancer , 2011, DOI: 10.4061/2011/618757
Abstract: N-methyl-N-nitrosourea (MNU) induces estrogen-dependent mammary tumors in female Lewis rats. We explored the antineoplastic activity of a synthetic androstane derivative, 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235), as a single agent or in combination with docetaxel compared to tamoxifen, anastrazole, and docetaxel monotherapies against MNU-induced mammary tumors in female Lewis rats. Treatment with HE3235 alone rapidly reduced tumor burden, similar in effect to tamoxifen and anastrozole. The combination of HE3235 with docetaxel was more effective than any single agent, although without apparent toxicity. Only HE3235 or HE3235 plus docetaxel continued to suppress tumor growth after cessation of treatment. HE3235 treatment increased immunohistochemical markers of apoptosis and expression of proapoptotic genes and estrogen receptor beta and decreased expression of antiapoptotic genes, androgen receptor, and estrogen receptor alpha. These data warrant clinical investigation of HE3235 for breast cancer treatment. 1. Introduction Breast cancer is one of the most common cancers among women, and the incidence of breast cancer is increasing worldwide [1]. Approximately 200,000 women are diagnosed with breast cancer annually, with an associated mortality of 40,000 in the United States [2]. Currently, there are few treatments for hormone-dependent breast cancer, with tamoxifen and anastrazole being the most widely used therapies [3]. Although generally well tolerated, these treatments can be associated with significant morbidity [4], and development of resistance is common [5, 6]. The carcinogen N-methyl-N-nitrosourea (MNU) induc-es hormone-dependent mammary tumors in rats. This model has previously been used to develop tamoxifen therapy in women with breast cancer [7], and is considered to be appropriate for studies of novel compounds potentially useful for the treatment of breast cancer. Substantial evidence suggests that this rodent model system mimics human breast cancer: the initiation of cancer occurs primarily at the same site in both humans and rats, the majority of the tumors express estrogen and progesterone receptors, and tumor development is dependent on the reproductive history, diet, and hormonal milieu [8]. Thus the model provides an opportunity to examine cause-and-effect relationships of the in situ environment fully impacted by systemic factors [9]. 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235) is a synthetic androstane derivative that inhibits 5-androstene-diol [10], testosterone, and estrogen (unpublished) stimulated prostate cancer cell
5-Androstene-3β,7β,17β-triol (β-AET) Slows Thermal Injury Induced Osteopenia in Mice: Relation to Aging and Osteoporosis
Ajay K. Malik,Sophia Khaldoyanidi,Dominick L. Auci,Scott C. Miller,Clarence N. Ahlem,Christopher L. Reading,Theodore Page,James M. Frincke
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013566
Abstract: 5-androstene-3β,7β,17β-triol (β-AET), an active metabolite of dehydroepiandrosterone (DHEA), reversed glucocorticoid (GC)-induced suppression of IL-6, IL-8 and osteoprotegerin production by human osteoblast-like MG-63 cells and promoted osteoblast differentiation of human mesenchymal stem cells (MSCs). In a murine thermal injury model that includes glucocorticoid-induced osteopenia, β-AET significantly (p<0.05) preserved bone mineral content, restored whole body bone mineral content and endochondral growth, suggesting reversal of GC-mediated decreases in chondrocyte proliferation, maturation and osteogenesis in the growth plate. In men and women, levels of β-AET decline with age, consistent with a role for β-AET relevant to diseases associated with aging. β-AET, related compounds or synthetic derivatives may be part of effective therapeutic strategies to accelerate tissue regeneration and prevent or treat diseases associated with aging such as osteoporosis.
Using Generalizability Theory to Evaluate the Applicability of a Serial Bayes Model in Estimating the Positive Predictive Value of Multiple Psychological or Medical Tests  [PDF]
Clarence D. Kreiter
Psychology (PSYCH) , 2010, DOI: 10.4236/psych.2010.13026
Abstract: Introduction: It is a common finding that despite high levels of specificity and sensitivity, many medical tests are not highly effective in diagnosing diseases exhibiting a low prevalence within a clinical population. What is not widely known or appreciated is how the results of retesting a patient using the same or a different medical or psychological test impacts the estimated probability that a patient has a particular disease. In the absence of a ‘gold standard’ spe-cial techniques are required to understand the error structure of a medical test. Generalizability can provide guid-ance as to whether a serial Bayes model accurately updates the positive predictive value of multiple test results. Methods: In order to understand how sources of error impact a test’s outcome, test results should be sampled across the testing conditions that may contribute to error. A generalizability analysis of appropriately sampled test results should allow researchers to estimate the influence of each error source as a variance component. These results can then be used to determine whether, or under what conditions, the assumption of test independence can be approximately satisfied, and whether Bayes theorem accurately updates probabilities upon retesting. Results: Four hypothetical generalizability study outcomes are displayed as variance component patterns. Each pattern has a different practical implication related to achieving independence between test results and deriving an enhanced PPV through retesting an individual patient. Discussion: The techniques demonstrated in this article can play an important role in achieving an enhanced positive predictive value in medical and psychological diagnostic testing and can help ensure greater confidence in a wide range of testing contexts.
Noun Phrase Cohesion in English Discourse: a Corpus-based Analysis of Patterns and Influences
Clarence Green
International Journal of English Linguistics , 2012, DOI: 10.5539/ijel.v2n4p44
Abstract: This study investigated the patterns of noun phrase cohesion in English discourse, with a specific interest in the role of the different clause types. Using corpus methodology, the study synthesized into a single framework for analysis the central features of previous research regarding cohesive devices, preferred argument structure, genre, information packaging and clause structure. A corpus of 1206 noun phrases was coded for factors drawn from previous research, starting with whether or not the NP contained old/cohesive information. Results of frequency cross-tabulations and a factor analysis indicated that preferred argument structure, noun phrase form, and discourse genre were more significant influences on patterns of noun phrase cohesion in English discourse than clause structure. However, patterns of cohesive noun phrases according to the distance to their antecedents revealed that the more grammatically integrated clauses, such embedded infinitival clauses, the fewer cohesive noun phrases with antecedents in the immediate context they tended to have. This indicated that at the local inter-clausal level noun phrase cohesion and the level of grammatical integration of a combined clause existed in somewhat complementary distribution. Conclusions drawn included that clause grammar codes cohesion locally, displacing the need for noun phrases to mark cohesion in the immediate discourse. The study therefore quantitatively supports previous theories that discourse cohesion and the different types of combined clauses in English exist along a continuum from grammar to discourse.
The end of literature: Reflections on literature and ethics
Clarence Walhout
Koers : Bulletin for Christian Scholarship , 1996, DOI: 10.4102/koers.v61i1.583
Abstract: Metaphysical scepticism and historical consciousness have sharpened our awareness of the limitations of language and rational discourse. This emphasis in critical theory offers a challenge to the Christian literary critic. Reflection on the nature and importance of teleology provides a way of refocusing criticism on the centrality of ethics rather than on truth claims in the study of literature. Using Ricoeur as a counter to the scepticism of Derrida, Christian literary theory can find a way to situate itse lf in the postmodern world. By understanding teleology in the context of narrative theory, as opposed to the contexts of eschatology and utopia, Christian theory can find a way of recovering the place of religion and ethics in literary criticism.
A Computational Investigation of Cohesion and Lexical Network Density in L2 Writing
Clarence Green
English Language Teaching , 2012, DOI: 10.5539/elt.v5n8p57
Abstract: This study used a new computational linguistics tool, the Coh-Metrix, to investigate and measure the differences in cohesion and lexical network density between native speaker and non-native speaker writing, as well as to investigate L2 proficiency level differences in cohesion and lexical network density. This study analyzed data from three corpora with the Coh-Metrix: the International Corpus of Learner English (ICLE) as an L2 higher proficiency group, the Louvain Corpus of Native English Essays (LOCNESS) as a native speaker baseline, and a collected EFL corpus from Indonesia for the L2 lower proficiency data. Statistical investigation of the Coh-Metrix results revealed that five out of six Coh-Metrix variables used in this study did not detect proficiency level differences in L2 but the tool was consistently able to distinguish between L2 and native speaker writing. Differences included that L2 writing contains more argument overlap, more semantic overlap, more frequent content words, fewer abstract verb hyponyms and less causal content than native speaker writing.
Azathioprine induced liver cirrhosis: An unusual side effect  [PDF]
Aida Ben Slama Trabelsi, Eya Hamami, Mehdi Ksiaa, Ahlem Souguir, Mohamed Ben Mabrouk, Ahlem Brahem, Ali Jmaa, Salem Ajmi
Open Journal of Gastroenterology (OJGas) , 2013, DOI: 10.4236/ojgas.2013.36050
Abstract: In recent years, the hepatotoxic potential of thiopurines, in particular 6-thioguanine (6-TG), has been discussed in literature. However, cirrhosis was exceptionally reported. We report the case of a 56-year-old woman with ileocaecal Crohn’s disease treated with azathioprine. After taking azathioprine (2 mg/kg daily) for four years, she underwent surgical treatment for acute intestinal obstruction. In peroperative, we noticed a cirrhotic liver. A surgical biopsy was performed and the diagnosis of cirrhosis was confirmed. Autoimmune and viral liver diseases were ruled out by laboratory parameters. Therefore, Azathioprine is believed to be the causative factor for inducing liver cirrhosis. Thus, treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle.
Cladistics, Bruchids and host plants: evolutionary interactions in amblycerus (Coleoptera: Bruchidae)
Jesús Romero Nápoles,Tina J. Ayers,Clarence Dan Johnson
Acta zoológica mexicana , 2002,
Abstract: Se presenta una análisis cladístico preliminar para 40 especies de Amblycerus Thunberg basado en 29 caracteres morfológicos. Se generaron cuatro árboles igualmente parsimoniosos de 60 pasos de longitud, con una consistencia de 0.63 y un índice de retención de 0.88. Remplazando en el cladograma cada una de las especies de Amblycerus por la familia de la planta huésped, fue posible formular una aproximación de la macroevolución en los taxones de los huéspedes. Al parecer estos brúquidos se han movido de la familia de plantas Fabaceae a 12 familias de otras plantas, principalmente Sterculiaceae y Boraginaceae. Varios factores, incluyendo el comportamiento de oviposición, se han citado para explicar algunos de los cambios de huésped. La bioquímica de la planta es especialmente importante, aunque solamente contamos con datos correlativos para soportar estas conclusiones. Para nosotros, la explicación más parsimoniosa sobre los cambios de huésped que observamos es por macroevolución durante ciertos periodos en la diversificación de los brúquidos en la época reciente.
De-Biasing the Dynamic Mode Decomposition for Applied Koopman Spectral Analysis
Maziar S. Hemati,Clarence W. Rowley,Eric A. Deem,Louis N. Cattafesta
Physics , 2015,
Abstract: The Dynamic Mode Decomposition (DMD)---a popular method for performing data-driven Koopman spectral analysis---has gained increased adoption as a technique for extracting dynamically meaningful spatio-temporal descriptions of fluid flows from snapshot measurements. Often times, DMD descriptions can be used for predictive purposes as well, which enables informed decision-making based on DMD model-forecasts. Despite its widespread use and utility, DMD regularly fails to yield accurate dynamical descriptions when the measured snapshot data are imprecise due to, e.g., sensor noise. Here, we express DMD as a two-stage algorithm in order to isolate a source of systematic error. We show that DMD's first stage, a subspace projection step, systematically introduces bias errors by processing snapshots asymmetrically. To remove this systematic error, we propose utilizing an augmented snapshot matrix in a subspace projection step, as in problems of total least-squares, in order to account for the error present in all snapshots. The resulting unbiased and noise-aware total DMD (TDMD) formulation reduces to standard DMD in the absence of snapshot errors, while the two-stage perspective generalizes the de-biasing framework to other related methods as well. TDMD's performance is demonstrated in numerical and experimental fluids examples.
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