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Search Results: 1 - 10 of 408504 matches for " Steven M. Watkins "
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1-(Adamantan-1-yl)-3-(4-methoxyphenyl)prop-2-en-1-oneCAS 174315-56-1.
Thy M. Nguyen,Frank R. Fronczek,Steven F. Watkins
Acta Crystallographica Section E , 2012, DOI: 10.1107/s1600536812032400
Abstract: The title molecule, C20H24O2, is a chalconoid derivative in which the keto–enone group is slightly distorted from planarity; the O=C—C=C torsion angle is 12.24 (13)°.
25,26-Bis(propan-2-ylidene)heptacyclo[20.2.1.110,13.02,21.03,8.09,14.015,20]hexacosa-2(21),3,5,7,9(14),11,15,17,19,23-decaene
Stefan M. Cooper,Tamara R. Schaller Nauman,Frank R. Fronczek,Steven F. Watkins
Acta Crystallographica Section E , 2012, DOI: 10.1107/s1600536812018211
Abstract: In the title compound, C32H28, the central cyclooctatetraene ring has a boat conformation, and the molecule is saddle shaped. The seat is defined by the mean plane of the four-atom attachment points (r.m.s. deviation = 0.014 ) of the two bicycloheptenyl substituents. These substituents comprise the pommel and cantle, with each mean plane defined by four atoms proximate to the seat (r.m.s. deviations = 0.002 and 0.004 ). Relative to the seat, the pommel and cantle bend up 31.16 (4) and 29.40 (5)°, while the benzo units (flaps, r.m.s. deviations = 0.006 and 0.009 ) bend down 36.75 (4) and 38.46 (4)°. The mean planes of the dimethylethylidene units are almost perpendicular to the saddle seat, making dihedral angles 86.89 (4) and 88.01 (4)°.
Genomics of Post-Prandial Lipidomic Phenotypes in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study
Marguerite R. Irvin, Degui Zhi, Stella Aslibekyan, Steven A. Claas, Devin M. Absher, Jose M. Ordovas, Hemant K. Tiwari, Steve Watkins, Donna K. Arnett
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099509
Abstract: Background Increased postprandial lipid (PPL) response to dietary fat intake is a heritable risk factor for cardiovascular disease (CVD). Variability in postprandial lipids results from the complex interplay of dietary and genetic factors. We hypothesized that detailed lipid profiles (eg, sterols and fatty acids) may help elucidate specific genetic and dietary pathways contributing to the PPL response. Methods and Results We used gas chromatography mass spectrometry to quantify the change in plasma concentration of 35 fatty acids and 11 sterols between fasting and 3.5 hours after the consumption of a high-fat meal (PPL challenge) among 40 participants from the GOLDN study. Correlations between sterols, fatty acids and clinical measures were calculated. Mixed linear regression was used to evaluate associations between lipidomic profiles and genomic markers including single nucleotide polymorphisms (SNPs) and methylation markers derived from the Affymetrix 6.0 array and the Illumina Methyl450 array, respectively. After the PPL challenge, fatty acids increased as well as sterols associated with cholesterol absorption, while sterols associated with cholesterol synthesis decreased. PPL saturated fatty acids strongly correlated with triglycerides, very low-density lipoprotein, and chylomicrons. Two SNPs (rs12247017 and rs12240292) in the sorbin and SH3 domain containing 1 (SORBS1) gene were associated with b-Sitosterol after correction for multiple testing (P≤4.5*10?10). SORBS1 has been linked to obesity and insulin signaling. No other markers reached the genome-wide significance threshold, yet several other biologically relevant loci are highlighted (eg, PRIC285, a co-activator of PPARa). Conclusions Integration of lipidomic and genomic data has the potential to identify new biomarkers of CVD risk.
Mutational Analysis of Hedgehog Signaling Pathway Genes in Human Malignant Mesothelioma
Chuan Bian Lim, Cecilia M. Prêle, Hui Min Cheah, Yuen Yee Cheng, Sonja Klebe, Glen Reid, D. Neil Watkins, Svetlana Baltic, Philip J. Thompson, Steven E. Mutsaers
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066685
Abstract: Background The Hedgehog (HH) signaling pathway is critical for embryonic development and adult homeostasis. Recent studies have identified regulatory roles for this pathway in certain cancers with mutations in the HH pathway genes. The extent to which mutations of the HH pathway genes are involved in the pathogenesis of malignant mesothelioma (MMe) is unknown. Methodology/Principal Findings Real-time PCR analysis of HH pathway genes PTCH1, GLI1 and GLI2 were performed on 7 human MMe cell lines. Exon sequencing of 13 HH pathway genes was also performed in cell lines and human MMe tumors. In silico programs were used to predict the likelihood that an amino-acid substitution would have a functional effect. GLI1, GLI2 and PTCH1 were highly expressed in MMe cells, indicative of active HH signaling. PTCH1, SMO and SUFU mutations were found in 2 of 11 MMe cell lines examined. A non-synonymous missense SUFU mutation (p.T411M) was identified in LO68 cells. In silico characterization of the SUFU mutant suggested that the p.T411M mutation might alter protein function. However, we were unable to demonstrate any functional effect of this mutation on Gli activity. Deletion of exons of the PTCH1 gene was found in JU77 cells, resulting in loss of one of two extracellular loops implicated in HH ligand binding and the intracellular C-terminal domain. A 3-bp insertion (69_70insCTG) in SMO, predicting an additional leucine residue in the signal peptide segment of SMO protein was also identified in LO68 cells and a MMe tumour. Conclusions/Significance We identified the first novel mutations in PTCH1, SUFU and SMO associated with MMe. Although HH pathway mutations are relatively rare in MMe, these data suggest a possible role for dysfunctional HH pathway in the pathogenesis of a subgroup of MMe and help rationalize the exploration of HH pathway inhibitors for MMe therapy.
Mastectomy Scar Boost Results in Low Risk of Locoregional Recurrence in the Setting of Close or Involved Surgical Margins  [PDF]
Laura Johnson, Natalie Lichter, Mamie Hextall, Patricia L. Watkins, Tarek A. Dufan, John M. Watkins
Journal of Cancer Therapy (JCT) , 2014, DOI: 10.4236/jct.2014.52020
Abstract:

Background: Several Phase III randomized trials have demonstrated improved local control and survival for post-mastectomy radiotherapy in patients with high-risk pathologic features. Close or involved surgical margins were not included as high-risk in these protocols, but have been associated with increased risk of local failure; however, the impact of a boost dose following chestwall radiotherapy in this setting remains to be determined. Methods: Retrospective single-institution outcomes analysis for patients with close or involved surgical margins treated with post-operative radiotherapy is followed by a boost. Results: Between 2003 and 2011, 34 patients were identified for inclusion in the present study. The median chestwall dose was 5040 cGy (range 5000 - 5040) and median boost dose was 1080 cGy (900 - 1620). At a median follow-up of 38.4 months (10.2 - 115.6; with 29% more than 5 years), 28 patients were alive without evidence of recurrence, 3 were alive with recurrent disease (1 chestwall), and 3 had died (none with recurrent disease). The 3-year local control, disease-free survival, and overall survivals were 96.9%, 93.9%, and 93.1%, respectively. Conclusion: Chestwall radiotherapy plus boost results in low risk of early locoregional recurrence for women with close or involved surgical margin(s) at mastectomy. Further investigation of PMRT with or without boost in this setting is warranted.

The implications of extreme response style (ERS) for cross-cultural and comparative research
M. L. Watkins
South African Journal of Industrial Psychology , 1992, DOI: 10.4102/sajip.v18i1.537
Abstract: Cross-cultural research in which fivepoint, Likert-type and semantic-differential scales are utilized, is a popular research practice. Extreme response style (ERS) may contaminate the validity of research results, however this possibility is often ignored in behavioural science research. In this study, the influence of biographical variables on extreme response style and the contaminating effect thereof on the validity of research results is investigated. The results of the study reveal that culture separately, and interaction with age and gender has a meaningful influence on ERS when five-point scales are utilized. The underlying causes of the phenomenon can however not exclusively be ascribed to biographical variables. Opsomming Kruiskulturele navorsing waarin vyfpunt, Likerttipe- en semanties-differensiale skale benut word, is 'n bekende navorsingspraktyk. Ekstreme responsiestyl is egter daartoe in staat om die geldigheid van sondanige navorsingsresultate te kontamineer, maar hierdie moontlikheid word dikwels in die gedragswetenskaplike navorsingspraktyk geignoreer. In hierdie studie word ondersoek ingestel na die invloed van biografiese faktore op ekstreme responsiestyl en die kontaminerende effek daarvan op die geldigheid van navorsingsresultate. Daar is gevind dat kultuur in interaksie met ouderdom en geslag, ERS betekenisvol beinvloed wanneer vyfpuntskale gebruik word. Die onderliggende oorsake van die verskynsel kan egter nie uitsluitlik aan biografiese veranderlikes toegeskryf word nie.
The meaning of working in black and white managerial samples with specific reference to sense of entitlement
M. L. Watkins
South African Journal of Industrial Psychology , 1995, DOI: 10.4102/sajip.v21i1.580
Abstract: Wealth distribution and wealth creation are probably the most important challenges to be faced by South African government. At the organisational level, it will be required of each employee to accept responsibility for contributing to organisational success. The formation of multi-cultural work teams gives relevance to the study of meaning of work and specifically, to the sense of entitlement as a manifestation of a need for equity. In this study it was found that black managers experience a stronger sense of entitlement than their white colleagues/ which is ascribed to deprivation in the past. Although affirmative action could be implemented as a compensatory measure, the caveats involved make it imperative to consider other alternatives. Hence, it is proposed that management systems should be redesigned to promote egalitarianism in the workplace. Opsomming Die verdeling en skepping van welvaart is waarskynlik die belangrikste uitdagings wat die Suid-Afrikaanse regering die hoof moet bied. Op ondernemingsvlak sal daar dus van eike werknemer verwag word om verantwoordelikheid vir 'n betekenisvolle bydrae tot organisasie-sukses te aanvaar. Die vorming van multi-kulturele groepe skep relevansie vir die bestudering van die betekenis van werk, en spesifiek die sin vir geregtigdheid,1 as 'n manifestasie van 'n behoefte aan billikheid. In hierdie studie is daar gevind dat swart bestuurders 'n sterker sin vir geregtigdheid as hulle wit kollegas ervaar. Dit word aan deprivasie in die verlede toegeskryf. Ofskoon regstellende aksie as 'n kompenserende maatreel geimplementeer sou kon word, skep die leemtes hieraan verbonde 'n behoefte aan oorweging van alternatiewe moontlikhede. Daar word derhalwe aanbeveel dat bestuurstelsels herontwerp word om gelykheid in die werkpiek te bevorder.
Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment
Rima Kaddurah-Daouk, Rebecca A. Baillie, Hongjie Zhu, Zhao-Bang Zeng, Michelle M. Wiest, Uyen Thao Nguyen, Katie Wojnoonski, Steven M. Watkins, Miles Trupp, Ronald M. Krauss
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025482
Abstract: Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP) study: Full Range of Response (FR), and Good and Poor Responders (GPR) were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP), rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic profiles could provide valuable information about treatment outcomes and could contribute to a more personalized approach to therapy.
How Do I Regret Thee? Let Me Count My Alternatives: Regret and Decision Making in Intimate Relationships  [PDF]
Richard E. Mattson, Ana M. Franco-Watkins, Karlene Cunningham
Psychology (PSYCH) , 2012, DOI: 10.4236/psych.2012.39100
Abstract: It is unsurprising when dissatisfied couples separate, but happy couples also dissolve their relationship. A hypothesized precursor to such outcomes is the availability of a better alternative partner. The current study examined regret over one’s current partner selection as the possible mechanism by which better alternatives leads to partner switching in otherwise happy unions. An undergraduate sample (N = 94) was administered several questionnaires; which included measures of partner regret, relationship satisfaction, the availability of more attractive alternative partners, and the probability of switching to an alternative in the future. For relatively satisfied individuals, the presence of a better alternative elicited regrets about their currently selected partner that, in turn, predicted greater hypothetical intentions to partner switch. Less satisfied individuals also endorsed partner regret, but irrespective of whether a current alternative was actually available. Only relatively satisfied individuals without more attractive alternatives endorsed low partner regret and, subsequently, greater intentions to remain in their current relationship.
Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10
Erin D Milligan, Evan M Sloane, Stephen J Langer, Pedro E Cruz, Marucia Chacur, Leah Spataro, Julie Wieseler-Frank, Sayamwong E Hammack, Steven F Maier, Terence R Flotte, John R Forsayeth, Leslie A Leinwand, Raymond Chavez, Linda R Watkins
Molecular Pain , 2005, DOI: 10.1186/1744-8069-1-9
Abstract: Neuropathic pain is an especially difficult chronic pain syndrome to treat. No compounds are yet available that successfully resolve such pain [1-3]. To date, drug therapies developed for human neuropathic pain have targeted neurons. However, evidence has recently accumulated that pathological pain, including neuropathic pain, is dynamically and dramatically amplified as a result of spinal cord glial activation [4-6]. Spinal cord glia become activated as a consequence of inflammation and/or trauma to peripheral nerves [4,6]. This raises the intriguing possibility that finding ways to target glial activation, or its downstream consequences, may provide a novel approach for neuropathic pain control [5,7].Several glial-selective drugs have been successful in preventing or reversing neuropathic pain in animals, but none is optimal for clinical applications. For example, fluorocitrate is a selective astrocyte inhibitor [8,9]. While effective in blocking the induction of neuropathic pain in animals [10], fluorocitrate is inappropriate for human use due to inhibition of glial glutamate uptake and consequent seizures can occur [11]. Similarly, minocycline is a selective microglial inhibitor [12]. It too is effective in blocking the induction of neuropathic pain in animals [13,14]. However, as minocycline fails to affect established neuropathic pain [13,14], this compound does not appear to have therapeutic potential.Other approaches have focused on the fact that glia are "immune cell-like". Upon activation, glia and immune cells each release pro-inflammatory substances, most notably pro-inflammatory cytokines (interleukin [IL]-1, tumor necrosis factor [TNF] and IL-6). The release of pro-inflammatory cytokines by activated spinal cord glia is key as these cytokines enhance pain and have been implicated in the initiation and maintenance of neuropathic pain [10,15,16]. Immunosuppressive (methotrexate) and immunomodulatory (propentofylline) drugs have been tested with the aim o
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