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Search Results: 1 - 10 of 169615 matches for " Joanna E. Merriam "
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The ERCC6 Gene and Age-Related Macular Degeneration
Dominique C. Baas,Dominiek D. Despriet,Theo G. M. F. Gorgels,Julie Bergeron-Sawitzke,André G. Uitterlinden,Albert Hofman,Cornelia M. van Duijn,Joanna E. Merriam,R. Theodore Smith,Gaetano R. Barile,Jacoline B. ten Brink,Johannes R. Vingerling,Caroline C. W. Klaver,Rando Allikmets,Michael Dean,Arthur A. B. Bergen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013786
Abstract: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS.
Quantum Relativity: Physical Laws Must be Invariant Over Quantum Systems
Paul Merriam
Physics , 2005,
Abstract: Decoherence may not solve all of the measurement problems of quantum mechanics. It is proposed that a solution to these problems may be to allow that superpositions describe physically real systems in the following sense. Each quantum system "carries" around a local spacetime in whose terms other quantum systems may take on nonlocal states. Each quantum system forms a physically valid coordinate frame. The laws of physics should be formulated to be invariant under the group of allowed transformations among such frames. A transformation of relatively superposed spatial coordinates that allows an electron system to preserve the de Broglie Relation in describing a double-slit laboratory system-in analogy to a Minkowskian Transformation-is proposed. In general, "quantum relativity" says is invariant under transformations among quantum reference frames. Some conjectures on how this impacts gravity and gauge invariance are made.
Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer
Merriam PA, Sikov WM
Breast Cancer: Targets and Therapy , 2011, DOI: http://dx.doi.org/10.2147/BCTT.S12150
Abstract: ical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer Review (2409) Total Article Views Authors: Merriam PA, Sikov WM Published Date October 2011 Volume 2011:3 Pages 139 - 150 DOI: http://dx.doi.org/10.2147/BCTT.S12150 Priscilla Merriam, William M Sikov Department of Medicine, Division of Hematology-Oncology, Warren Alpert Medical School of Brown University, Providence, RI, USA Abstract: Breast cancers that overexpress human epidermal growth factor receptor-2 (HER2-positive [HER2+]) tend to be biologically aggressive and associated with a poor prognosis, even those that coexpress receptors for estrogen and/or progesterone (hormone receptor-positive [HR+]). Optimal therapy for patients with “double-positive” (HR+/HER2+) breast cancers is still being defined. In this subset of patients, the efficacy of targeted endocrine therapies appears to be diminished by cross-activation or “crosstalk” between estrogen receptor-mediated gene transcription and pathways activated by other growth factor receptors, including HER2. Lapatinib is a tyrosine kinase inhibitor which binds reversibly to the intracellular domains of the epidermal growth factor receptor and HER2, interfering with their ability to initiate signal transduction cascades that promote cancer cell proliferation, survival, and metastasis. In a recently published randomized, placebo-controlled Phase III study in postmenopausal HR+ metastatic breast cancer, the addition of lapatinib to the aromatase inhibitor letrozole significantly improved progression-free survival solely in women who were also HER2+. This article reviews the biology of “double-positive” breast cancers and the rationale underlying combining endocrine and HER2-targeted therapies, including the lapatinib/letrozole combination, for these tumors. Results from the Phase III trial are examined, as well as available data on other combinations of HR and HER2-targeted therapies. Ongoing trials and potential future applications of these combinations in both HR+/HER2+ and other subgroups of breast cancer patients are also discussed.
Clinical utility of the combination of lapatinib and letrozole in the management of hormone receptor-positive and HER2-positive advanced breast cancer
Merriam PA,Sikov WM
Breast Cancer: Targets and Therapy , 2011,
Abstract: Priscilla Merriam, William M Sikov Department of Medicine, Division of Hematology-Oncology, Warren Alpert Medical School of Brown University, Providence, RI, USA Abstract: Breast cancers that overexpress human epidermal growth factor receptor-2 (HER2-positive [HER2+]) tend to be biologically aggressive and associated with a poor prognosis, even those that coexpress receptors for estrogen and/or progesterone (hormone receptor-positive [HR+]). Optimal therapy for patients with “double-positive” (HR+/HER2+) breast cancers is still being defined. In this subset of patients, the efficacy of targeted endocrine therapies appears to be diminished by cross-activation or “crosstalk” between estrogen receptor-mediated gene transcription and pathways activated by other growth factor receptors, including HER2. Lapatinib is a tyrosine kinase inhibitor which binds reversibly to the intracellular domains of the epidermal growth factor receptor and HER2, interfering with their ability to initiate signal transduction cascades that promote cancer cell proliferation, survival, and metastasis. In a recently published randomized, placebo-controlled Phase III study in postmenopausal HR+ metastatic breast cancer, the addition of lapatinib to the aromatase inhibitor letrozole significantly improved progression-free survival solely in women who were also HER2+. This article reviews the biology of “double-positive” breast cancers and the rationale underlying combining endocrine and HER2-targeted therapies, including the lapatinib/letrozole combination, for these tumors. Results from the Phase III trial are examined, as well as available data on other combinations of HR and HER2-targeted therapies. Ongoing trials and potential future applications of these combinations in both HR+/HER2+ and other subgroups of breast cancer patients are also discussed. Keywords: breast neoplasm, erbB2, estrogen receptor, letrozole, lapatinib
Optimization of the A Constant for the SRK/T Formula  [PDF]
John C. Merriam, Eva Nong, Lei Zheng, Malka Stohl
Open Journal of Ophthalmology (OJOph) , 2015, DOI: 10.4236/ojoph.2015.53017
Abstract: Purpose: To evaluate the effect of axial length (AL) and the average preoperative keratometry (K) on the A constant in the SRK/T formula. Methods: The retrospective, comparative case series includes 635 eyes from 407 cataract patients from Columbia University Medical Center from January 2006 to August 2010, operated by a single surgeon using a temporal incision and the Acrysof SN60WF IOL (Alcon Laboratories, TX). Using the postoperative manifest refraction and biometry data, we calculated the precise A constant (Ap) necessary to yield the postoperative spherical equivalent for each eye. To optimize the A constant, we developed three regression models (linear, quadratic, and categorical in 7 AL groups) to relate these precise A constants to AL and K. We verified our method with another series of 45 eyes for which we calculated mean errors (defined as the difference between the spherical equivalent of the postoperative refraction and the predicted postoperative refraction) using the optimized and manufacturer’s suggested A constants. Results: There is a statistically significant relationship between AL (P < 0.001), K (P < 0.001) and the A constant. Ap increased as AL increased and as K decreased. In the validation data set, optimizing the A constant reduced mean errors from 0.50 D to 0.25 D and also reduced hyperopic refractive outcomes. Conclusions: The A constant for longer eyes with flatter corneas is larger than the A constant for shorter eyes with steeper corneas. Optimizing A constants using both AL and K improved the predictability of refractive outcomes without modification to the SRK/T formula.
The Eukaryotic Mismatch Recognition Complexes Track with the Replisome during DNA Synthesis
Joanna E. Haye?,Alison E. Gammie
PLOS Genetics , 2015, DOI: 10.1371/journal.pgen.1005719
Abstract: During replication, mismatch repair proteins recognize and repair mispaired bases that escape the proofreading activity of DNA polymerase. In this work, we tested the model that the eukaryotic mismatch recognition complex tracks with the advancing replisome. Using yeast, we examined the dynamics during replication of the leading strand polymerase Polε using Pol2 and the eukaryotic mismatch recognition complex using Msh2, the invariant protein involved in mismatch recognition. Specifically, we synchronized cells and processed samples using chromatin immunoprecipitation combined with custom DNA tiling arrays (ChIP-chip). The Polε signal was not detectable in G1, but was observed at active origins and replicating DNA throughout S-phase. The Polε signal provided the resolution to track origin firing timing and efficiencies as well as replisome progression rates. By detecting Polε and Msh2 dynamics within the same strain, we established that the mismatch recognition complex binds origins and spreads to adjacent regions with the replisome. In mismatch repair defective PCNA mutants, we observed that Msh2 binds to regions of replicating DNA, but the distribution and dynamics are altered, suggesting that PCNA is not the sole determinant for the mismatch recognition complex association with replicating regions, but may influence the dynamics of movement. Using biochemical and genomic methods, we provide evidence that both MutS complexes are in the vicinity of the replisome to efficiently repair the entire spectrum of mutations during replication. Our data supports the model that the proximity of MutSα/β to the replisome for the efficient repair of the newly synthesized strand before chromatin reassembles.
Association between Depression and C-Reactive Protein
Yunsheng Ma,David E. Chiriboga,Sherry L. Pagoto,Milagros C. Rosal,Wenjun Li,Philip A. Merriam,James R. Hébert,Matthew C. Whited,Ira S. Ockene
Cardiology Research and Practice , 2011, DOI: 10.4061/2011/286509
Abstract: Objective. Depression has been associated with increased cardiovascular disease risk, and a depression-related elevation of high sensitivity C-reactive protein (hs-CRP) has been proposed as a possible mechanism. The objective of this paper is to examine association between depression and high sensitivity C-reactive protein (hs-CRP). Methods. Subjects consisted of 508 healthy adults (mean age 48.5 years; 49% women, 88% white) residing in central Massachusetts. Data were collected at baseline and at quarterly intervals over a one-year period per individual. Multivariable linear mixed models were used to assess the association for the entire sample and by gender. Results. The mean Beck Depression Inventory score was 5.8 (standard deviation (SD) 5.4; median 4.3), and average serum hs-CRP was 1.8 mg/L (SD 1.7; median 1.2). Results from the multivariable linear mixed models show that individuals with higher depression scores have higher levels of hs-CRP. Analyses by gender show persistence of an independent association among women, but not among men. Body mass index (BMI = weight(kg)/height(m)2) appears to be a partial mediator of this relationship. Conclusion. Depression score was correlated to hs-CRP levels in women. Further studies are required to elucidate the biological mechanisms underlying these associations and their implications.
Participation and Activity Rates: Monitoring Exposure Potential for Native Americans and Others in the United States  [PDF]
Joanna Burger
Journal of Environmental Protection (JEP) , 2011, DOI: 10.4236/jep.2011.28116
Abstract: Managers and regulators are concerned about potential human health effects from exposure on lands contaminated by chemicals and radionuclides. Determining target cleanup levels is partly dependent upon future land use, and potential exposure from human use. This paper provides data from surveys of activity patterns of people attending festivals in four states, located in the vicinity of Department of Energy facilities. There were significant differences in both participation rates, and activity rates as a function of both location and ethnicity that can be used by managers to track exposure, land use, and preferred activities on natural lands. In general, 1) a higher percent of Native Americans engaged in consumptive activities than others, 2) a higher percent of Caucasians engaged in some non-consumptive activities than Native Americans, 3) a higher percentage of Native Americans engaged in activities on sacred grounds, 4) activity rates were generally higher for Native Americans for consumptive activities and religious/cultural than for Caucasians, 5) fishing rates were higher than other consumptive activities, and camping/hiking were higher than other non-con- sumptive activities, and 6) hunting rates were higher in subjects from Idaho than elsewhere. Baseline human use is critical for monitoring potential exposure, and provides the basis for monitoring, risk assessment and future land use, and these data can be used by managers for assessment and management. Tracking changes over time will reflect changing recreational, subsistence, and cultural/religious trends that relate to land use, public perceptions, and exposure.
In-Arrears Interest Rate Derivatives under the 3/2 Model  [PDF]
Joanna Goard
Modern Economy (ME) , 2015, DOI: 10.4236/me.2015.66067
Abstract: Lie symmetry methods are used to find a closed form solution for in-arrears swaps under the 3/2 model \"\". As well, approximate solutions are found for short-tenor in-arrears caplets and floorlets under the same interest rate model. Comparisons are made of the approximate option values with those obtained with a computationally-intensive numerical scheme. The approximate pricing is found to be substantially fast and easy to implement, while the relative errors with respect to the “true” prices are very small.
Quantitative analysis of DNA methylation at all human imprinted regions reveals preservation of epigenetic stability in adult somatic tissue
Kathryn Woodfine, Joanna E Huddleston, Adele Murrell
Epigenetics & Chromatin , 2011, DOI: 10.1186/1756-8935-4-1
Abstract: Remarkable stability of the DNA methylation imprint was observed in all germ-line DMRs and paternally methylated somatic DMRs (which maintained average methylation levels of between 35% - 65% in all somatic tissues, independent of gene expression). Maternally methylated somatic DMRs were found to have more variation with tissue specific methylation patterns. Most DMRs, however, showed some intra-individual variability for DNA methylation levels in peripheral blood, suggesting that more than one DMR needs to be examined in order to get an overall impression of the epigenetic stability in a tissue. The plasticity of DNA methylation at imprinted genes was examined in a panel of normal and cancer cell lines. All cell lines showed changes in DNA methylation, especially at the paternal germ-line and the somatic DMRs.Our validated pyrosequencing methylation assays can be widely used as a tool to investigate DNA methylation levels of imprinted genes in clinical samples. This first comprehensive analysis of normal methylation levels in adult somatic tissues at human imprinted regions confirm that, despite intra-individual variability and tissue specific expression, imprinted genes faithfully maintain their DNA methylation in healthy adult tissue. DNA methylation levels of a selection of imprinted genes are, therefore, a valuable indicator for epigenetic stability.DNA methylation levels at gene promoters and Cytosine-phosphate guanine (CpG) islands associated with gene regulatory regions undergo dynamic changes during differentiation and can vary between normal tissues [1]. In cancer cells epigenetic programming results in global methylation changes [2] and it is difficult to ascertain which methylation changes are abnormal without knowing what normal baseline methylation profiles are for the tissue from which the cancer originates [3]. Since aberrant DNA methylation is thought to be an early indicator of cancer, it will be useful to have a series of reporter loci to indicate
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