Dr. James Lyons-Weiler, PhD - The Institute for Pure and Applied Knowledge - CEO/Director

Dr. James Lyons-Weiler

PhD

The Institute for Pure and Applied Knowledge

CEO/Director

ALLISON PARK, PA | United States

ORCID logohttps://orcid.org/0000-0001-9343-7508

Dr. James Lyons-Weiler, PhD - The Institute for Pure and Applied Knowledge - CEO/Director

Dr. James Lyons-Weiler

PhD

Introduction

Dr. Lyons-Weiler is a Pittsburgh-area scientist. He is a biologist, geneticist, lecturer, and author, who has worked collaboratively for over twenty years on more than one hundred research studies in the areas of biological diversity, cancer, diabetes, heart disease, infectious disease, autism and other aspects of clinical, biomedical and translational research. He now focuses on causes of autism, autoimmunity and gastrointestinal disorders.

Dr Lyons-Weiler was the Founding Editor-in-Chief of the open access, peer-reviewed research journal Cancer Informatics. He is an expert in study design, multivariate data analysis, genetics and systems biology. He has authored three books: “Ebola: An Evolving Story,” “Cures vs. Profits: Successes in Translational Research”. For his latest book, “The Environmental and Genetic Causes of Autism,” he reviewed over 3,000 research studies, and cited more than 2,000 of these studies in the published work. He is currently the CEO and Director of The Institute for Pure and Applied Knowledge.

Primary Affiliation: The Institute for Pure and Applied Knowledge - ALLISON PARK, PA , United States

Research Interests:


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Publications

47Publications

900Reads

93Profile Views

386PubMed Central Citations

Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Heterogeneous Genetic Predisposition

Autism Open Access 8(1):1-15.

Autism Open Access

Neurodevelopmental disorders, including Autism Spectrum Disorders, have a complex biological and medical basis involving diverse genetic risk and myriad environmental exposures. Teasing apart the role of specific stressors is made challenging due to the large number of apparently contributing associations, gene X environment interactions and phenomimicry [1]. Historically, these conditions have been rare, making causality assessment at the population level infeasible. Only a few vaccines have been tested for association with autism, and it has been shown that improved diagnosis only explains a percentage of the increase in diagnosis. Now, the rates are so high in some countries that public school programs cannot handle the large numbers of special needs students, and professionals are quitting their jobs due to security concerns. Here, I review evidence of the pathophysiology of autism that reconciles the apparent paradox between the high degree of causal heterogeneity in environmental toxins, the absence of common "autism gene," and the high degree of genetic concordance (heritability) of ASD and ASD-like traits. In brief, the sampling of environmental toxins, and thus the environmental toxin sampling liability for ASD varies among families involving different local exposures following injury to normal cellular endoplasmic detoxification and mitochondrial processes from toxic metals. The literature strongly supports that autism is most accurately seen as an acquired cellular detoxification deficiency syndrome with heterogeneous genetic predisposition that manifests pathophysiologic consequences of accumulated, run-away cellular toxicity. At a more general level, it is a form of a toxicant-induced loss of tolerance of toxins, and of chronic and sustained ER overload (ER hyper stress), contributing to neuronal and glial apoptosis via the unfolded-protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal retoxification in neurons and glial cells accompanied by chronic UPR is key. This model explains the aberrant protein disorder observed in ASD; the great diversity of genes that are found to have low, but real contributions to ASD risk and the sensitivity of individuals with ASD to environmental toxins. The hindrance of detoxification and loss of cellular energetics leads to apoptosis, release of cytokines and chronic neuroinflammation and microglial activation, all observed hallmarks of ASD. Interference with the development of normal complex (redundant) synapses leads to a pathological variation in neuronal differentiation, axon and dendrite outgrowth, and synaptic protein expression. The most general outcomes are overall simplification of gross synaptic anatomy and, neurofunctionally, a loss of inhibitory feedback and aberrations in long-term connections between distant regions of the brain. Failed resolution of the ER stress response leads to re-distribution of neurotoxic metals, and the impaired neurocellular processes lead to subsequent accumulation of a variety of additional types of toxins with secondary, sometime life-threatening comorbidities such as seizures, with overlapping (not mutually exclusive) causality. Reduction of exposure to toxins known to cause mitopathy (mercury) and endoplasmic reticulum dysfunction (mercury and aluminum) during pregnancy and during the early years of development will reduce the risk of ER overload and ER hyper stress, and of ASD diagnosis. This knowledge has immediate clinical translational relevance: post-vaccination symptoms should be heeded as a sign of susceptibility to toxin; Vitamin D can be increased to drive the healthy early phases of the UPR, and mutations in ASD genes encoding proteins with high intrinsic disorder may contraindicate the use of aluminum and mercury for carriers of risk alleles. Clinicians should be alert to a patient’s Vitamin D receptor (BSM) mutational status prior to recommending increased doses. Approaches to improving overall brain health in autistics must be de-stigmatized and given high priority. Reduction of lifetime exposures of industrial and agricultural toxins will improve brain health for the entire human population. Purely genetic studies of ASD, and studies that do not include vaccination as an environmental exposure with potential liability and interactions with genes, are unethical. To qualify as science, studies must test plausible hypotheses, and the absence of association from poorly designed, unethically executed, and underpowered and unsound whole-population association studies have been harmful distractions in the quest for understanding. Skilled paediatricians and ob/gyns will seek evidence of genetic predisposition to environmental susceptibility in the form of non-synonymous substitutions in brain proteins that require ER-folding, and they will provide informed cautions on exposures (from all sources) to environmental toxins to patients and parents of patients with signs of metal and chemical sensitivity. To aid in this, a list of ASD environmental susceptibility protein-encoded genes is presented. A clinical Exome sequence test, followed by loss of function prediction analysis, would point to individuals most susceptible to vaccine metal-induced ER hyper stress leading to failed cellular detoxification.

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October 2018
193 Reads

Reconsideration of the immunotherapeutic pediatric safe dose levels of aluminum.

J Trace Elem Med Biol 2018 Jul 8;48:67-73. Epub 2018 Mar 8.

Hale O'mana'o Research, 19 West Edwards Street, Edmond, OK 73003, United States. Electronic address:

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http://dx.doi.org/10.1016/j.jtemb.2018.02.025DOI Listing
July 2018
27 Reads
2.491 Impact Factor

DNA methylation in the pathophysiology of hyperphenylalaninemia in the PAH(enu2) mouse model of phenylketonuria.

Mol Genet Metab 2016 09 14;119(1-2):1-7. Epub 2016 Jan 14.

Department of Pathology, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, United States.

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http://dx.doi.org/10.1016/j.ymgme.2016.01.001DOI Listing
September 2016
23 Reads
2 Citations
2.625 Impact Factor

Altered DNA methylation in PAH deficient phenylketonuria.

Mol Genet Metab 2015 Jun-Jul;115(2-3):72-7. Epub 2015 Apr 24.

Genomics and Proteomics Core Laboratories, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15260, United States.

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http://dx.doi.org/10.1016/j.ymgme.2015.04.002DOI Listing
March 2016
36 Reads
2.625 Impact Factor

Feature Selection for Classification of SELDI-TOF-MS Proteomic Profiles.

Appl Bioinformatics 2005 ;4(4):227-46

Department of Computer Science, University of Pittsburgh, Pittsburgh, Pennsylvania, USAUniversity of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.2165/00822942-200504040-00003DOI Listing
November 2015
8 Reads

Differential hippocampal gene expression and pathway analysis in an etiology-based mouse model of major depressive disorder.

Am J Med Genet B Neuropsychiatr Genet 2015 Jun 23;168B(4):316. Epub 2015 Mar 23.

Harvard Medical School, Massachusetts, Boston.

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http://dx.doi.org/10.1002/ajmg.b.32301DOI Listing
June 2015
12 Reads
3.416 Impact Factor

Direct regulation of diurnal Drd3 expression and cocaine reward by NPAS2.

Biol Psychiatry 2015 Mar 13;77(5):425-433. Epub 2014 Aug 13.

Department of Psychiatry and Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219.

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http://dx.doi.org/10.1016/j.biopsych.2014.07.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315729PMC
March 2015
15 Reads
10.255 Impact Factor

Methylome repatterning in a mouse model of Maternal PKU Syndrome.

Mol Genet Metab 2014 Nov 23;113(3):194-9. Epub 2014 Aug 23.

Genomics and Proteomics Core Laboratories, Bioinformatics Core, University of Pittsburgh, 3343 Forbes Avenue, Pittsburgh, PA 15260, USA.

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http://dx.doi.org/10.1016/j.ymgme.2014.08.006DOI Listing
November 2014
12 Reads
2.625 Impact Factor

Differential hippocampal gene expression and pathway analysis in an etiology-based mouse model of major depressive disorder.

Am J Med Genet B Neuropsychiatr Genet 2014 Sep 25;165B(6):457-66. Epub 2014 Jul 25.

Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania.

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http://dx.doi.org/10.1002/ajmg.b.32257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431889PMC
September 2014
8 Reads
3.416 Impact Factor

The effect of environmental enrichment on substantia nigra gene expression after traumatic brain injury in rats.

J Neurotrauma 2013 Feb 5;30(4):259-70. Epub 2013 Feb 5.

Brain Trauma Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

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http://dx.doi.org/10.1089/neu.2012.2462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579325PMC
February 2013
9 Reads
3.714 Impact Factor

Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement.

Biochem Biophys Res Commun 2012 Sep 7;425(4):873-9. Epub 2012 Aug 7.

Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

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http://dx.doi.org/10.1016/j.bbrc.2012.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007057PMC
September 2012
14 Reads
2.297 Impact Factor

Variations in discovery-based preeclampsia candidate genes.

Clin Transl Sci 2012 Aug 15;5(4):333-9. Epub 2012 May 15.

Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1111/j.1752-8062.2012.00413.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419489PMC
August 2012
8 Reads
2.110 Impact Factor

Assessing the statistical significance of the achieved classification error of classifiers constructed using serum peptide profiles, and a prescription for random sampling repeated studies for massive high-throughput genomic and proteomic studies.

Cancer Inform 2005 ;1:53-77

Department of Pathology, Cancer Biomarkers Laboratory, Center for Pathology Informatics, Benedum Oncology Informatics Center, University of Pittsburgh Cancer Institute University of Pittsburgh, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657655PMC
July 2011
10 Reads

Efficiency analysis of competing tests for finding differentially expressed genes in lung adenocarcinoma.

Cancer Inform 2008 14;6:389-421. Epub 2008 Jul 14.

Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA 15260, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2623303PMC
http://dx.doi.org/10.4137/cin.s791DOI Listing
May 2010
6 Reads

Cellular factors associated with latency and spontaneous Epstein-Barr virus reactivation in B-lymphoblastoid cell lines.

Virology 2010 Apr 11;400(1):53-67. Epub 2010 Feb 11.

Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 435 Parran Hall, 130 DeSoto Street, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1016/j.virol.2010.01.002DOI Listing
April 2010
8 Reads
3.321 Impact Factor

Evaluation of the Consensus of Four Peptide Identification Algorithms for Tandem Mass Spectrometry Based Proteomics.

J Proteomics Bioinform 2010 Feb;3:39-47

Department of Pathology, University of Pittsburgh, PA.

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http://dx.doi.org/10.4172/jpb.1000119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892992PMC
February 2010
7 Reads
9 Citations

Determining the statistical significance of survivorship prediction models.

J Eval Clin Pract 2010 Feb;16(1):155-65

Biomedical Informatics Training Program, Department of Biomedical Informatics, Pittsburgh, PA 15260, USA.

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http://dx.doi.org/10.1111/j.1365-2753.2009.01199.xDOI Listing
February 2010
10 Reads
1.580 Impact Factor

Optimization of the Use of Consensus Methods for the Detection and Putative Identification of Peptides via Mass Spectrometry Using Protein Standard Mixtures.

J Proteomics Bioinform 2009 Jun;2(6):262-273

Bioinformatics Analysis Core, Genomics and Proteomics Core Laboratories and Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA.

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http://dx.doi.org/10.4172/jpb.1000085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749508PMC
June 2009
9 Reads

Altered global gene expression in first trimester placentas of women destined to develop preeclampsia.

Placenta 2009 Jan 21;30(1):15-24. Epub 2008 Nov 21.

School of Nursing, Department of Health Promotion and Development, University of Pittsburgh, Pittsburgh, PA 15261, USA.

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http://dx.doi.org/10.1016/j.placenta.2008.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667803PMC
January 2009
6 Reads
2.710 Impact Factor

Wrapper consistency analysis: a measure of consistency in a wrapper setting.

AMIA Annu Symp Proc 2008 Nov 6:1011. Epub 2008 Nov 6.

Department of Biomedical Informatics, University of Pittsburg, USA.

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November 2008
5 Reads

Heritability of oral microbial species in caries-active and caries-free twins.

Twin Res Hum Genet 2007 Dec;10(6):821-8

New York University College of Dentistry, New York, NY 10010, USA.

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http://dx.doi.org/10.1375/twin.10.6.821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148892PMC
December 2007
13 Reads
1.918 Impact Factor

Intersession reproducibility of mass spectrometry profiles and its effect on accuracy of multivariate classification models.

Bioinformatics 2007 Nov 30;23(22):3065-72. Epub 2007 Aug 30.

Department of Computer Science, Intelligent Systems Program, University of Pittsburgh Cancer Institute and Genomics and Proteomics Core Laboratories, University of Pittsburgh, Pittsburgh, PA 15260, USA.

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http://dx.doi.org/10.1093/bioinformatics/btm415DOI Listing
November 2007
6 Reads
4.981 Impact Factor

Progression-associated genes in astrocytoma identified by novel microarray gene expression data reanalysis.

Methods Mol Biol 2007 ;377:203-22

Center for Cancer and Immunology Research, Children's Research Institute, Department of Hematology-Oncology, Children's National Medical Center, Washington, DC, USA.

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http://dx.doi.org/10.1007/978-1-59745-390-5_13DOI Listing
August 2007
8 Reads

Clinical decision modeling system.

BMC Med Inform Decis Mak 2007 Aug 13;7:23. Epub 2007 Aug 13.

Bioinformatics Analysis Core, Genomics and Proteomics Core Laboratories, 3343 Forbes Avenue, Pittsburgh, PA 15260 USA.

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http://dx.doi.org/10.1186/1472-6947-7-23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2131745PMC
August 2007
8 Reads
1.496 Impact Factor

Gene expression patterns in isolated keloid fibroblasts.

Wound Repair Regen 2006 Jul-Aug;14(4):463-70

Department of Pathology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1111/j.1743-6109.2006.00135.xDOI Listing
January 2007
7 Reads
2.745 Impact Factor

Molecular overlap of fly circadian rhythms and human pancreatic cancer.

Cancer Lett 2006 Nov 31;243(1):55-7. Epub 2006 Jan 31.

Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

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http://dx.doi.org/10.1016/j.canlet.2005.11.049DOI Listing
November 2006
10 Reads
5.621 Impact Factor

Proteomic analysis of urine in kidney transplant patients with BK virus nephropathy.

J Am Soc Nephrol 2006 Nov 11;17(11):3248-56. Epub 2006 Oct 11.

Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA.

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http://dx.doi.org/10.1681/ASN.2006050437DOI Listing
November 2006
8 Reads
9.343 Impact Factor

Hepatic gene expression response to acute indomethacin exposure.

Mol Diagn Ther 2006 ;10(3):187-96

Department of Pathology, University of Pittsburgh School of Medicine, Shadyside Hospital, Pittsburgh, Pennsylvania 15232, USA.

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http://dx.doi.org/10.1007/BF03256457DOI Listing
October 2006
41 Reads
2.891 Impact Factor

caGEDA: a web application for the integrated analysis of global gene expression patterns in cancer.

Appl Bioinformatics 2004 ;3(1):49-62

University of Pittsburgh Cancer Institute, University of Pittsburg Medical School, Pittsburg, PA 15232, USA.

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http://link.springer.com/content/pdf/10.2165/00822942-200403
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http://dx.doi.org/10.2165/00822942-200403010-00007DOI Listing
January 2006
9 Reads

Microbial risk indicators of early childhood caries.

J Clin Microbiol 2005 Nov;43(11):5753-9

University of Pittsburgh, School of Dental Medicine, Division of Pediatric and Developmental Dental Sciences, 3501 Terrace St., Room 386, Pittsburgh, PA 15261, USA.

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http://dx.doi.org/10.1128/JCM.43.11.5753-5759.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287835PMC
November 2005
11 Reads
3.993 Impact Factor

Prediction of lymph node metastasis by analysis of gene expression profiles in primary lung adenocarcinomas.

Clin Cancer Res 2005 Jun;11(11):4128-35

Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1158/1078-0432.CCR-04-2525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211271PMC
June 2005
16 Reads
8.722 Impact Factor

Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling.

Oncogene 2005 Mar;24(10):1774-87

Department of Surgery, University of Massachusetts Medical School, Worcester, MA 06105, USA.

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http://dx.doi.org/10.1038/sj.onc.1207991DOI Listing
March 2005
58 Reads
8.459 Impact Factor

Tests for finding complex patterns of differential expression in cancers: towards individualized medicine.

BMC Bioinformatics 2004 Aug 12;5:110. Epub 2004 Aug 12.

Department of Pathology, Center for Biomedical Informatics, and Interdisciplinary Biomedical Graduate Program, University of Pittsburgh, PA 15232 USA.

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http://dx.doi.org/10.1186/1471-2105-5-110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC514539PMC
August 2004
5 Reads
2.576 Impact Factor

Overcoming confounded controls in the analysis of gene expression data from microarray experiments.

Appl Bioinformatics 2003 ;2(4):197-208

Center for Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA 15232, USA.

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June 2004
6 Reads
8 Citations

Profound normalisation challenges remain in the analysis of data from microarray experiments.

Appl Bioinformatics 2003 ;2(4):193-5

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June 2004
9 Reads

A classification-based machine learning approach for the analysis of genome-wide expression data.

Genome Res 2003 Mar;13(3):503-12

Department of Biological Sciences, University of Massachusetts, Lowell, Massachusetts 01854, USA.

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http://dx.doi.org/10.1101/gr.104003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC430281PMC
March 2003
5 Reads
7 Citations
14.630 Impact Factor

Homocysteine, folate deprivation and Alzheimer neuropathology.

J Alzheimers Dis 2002 Aug;4(4):261-7

Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, Department of Health and Clinical Sciences, Department of Biochemistry, UMass, Lowell, Lowell, MA 01854, USA.

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http://dx.doi.org/10.3233/jad-2002-4401DOI Listing
August 2002
9 Reads
4.151 Impact Factor

Evolutionary origin, diversification and specialization of eukaryotic MutS homolog mismatch repair proteins.

Nucleic Acids Res 2000 Jan;28(2):463-71

Program in Molecular Biology, Oregan State University, Corvallis, OR 97331, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC102523PMC
http://dx.doi.org/10.1093/nar/28.2.463DOI Listing
January 2000
7 Reads
9.112 Impact Factor

Branch length heterogeneity leads to nonindependent branch length estimates and can decrease the efficiency of methods of phylogenetic inference.

J Mol Evol 1999 Sep;49(3):392-405

Institute of Molecular Evolutionary Genetics and Department of Biology, Pennsylvania State University, University Park, PA 16802-5301 USA.

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http://dx.doi.org/10.1007/pl00006563DOI Listing
September 1999
5 Reads
1.680 Impact Factor