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Medicine and Health Sciences

2015

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Articles 1 - 30 of 181

Full-Text Articles in Physical Sciences and Mathematics

Correction Of Verication Bias Using Log-Linear Models For A Single Binaryscale Diagnostic Tests, Haresh Rochani, Hani M. Samawi, Robert L. Vogel, Jingjing Yin Dec 2015

Correction Of Verication Bias Using Log-Linear Models For A Single Binaryscale Diagnostic Tests, Haresh Rochani, Hani M. Samawi, Robert L. Vogel, Jingjing Yin

Biostatistics Faculty Publications

In diagnostic medicine, the test that determines the true disease status without an error is referred to as the gold standard. Even when a gold standard exists, it is extremely difficult to verify each patient due to the issues of costeffectiveness and invasive nature of the procedures. In practice some of the patients with test results are not selected for verification of the disease status which results in verification bias for diagnostic tests. The ability of the diagnostic test to correctly identify the patients with and without the disease can be evaluated by measures such as sensitivity, specificity and predictive …


Direct Phenotypic Screening In Mice: Identification Of Individual, Novel Antinociceptive Compounds From A Library Of 734 821 Pyrrolidine Bis-Piperazines, Richard A. Houghten, Michelle L. Ganno, Jay P. Mclaughlin, Colette T. Dooley, Shainnel O. Eans Torrey Pines Institute For Molecular Studies, Radleigh Santos, Travis Lavoi, Adel Nefzi, Greg Welmaker, Marc A. Giulianotti, Lawrence Toll Dec 2015

Direct Phenotypic Screening In Mice: Identification Of Individual, Novel Antinociceptive Compounds From A Library Of 734 821 Pyrrolidine Bis-Piperazines, Richard A. Houghten, Michelle L. Ganno, Jay P. Mclaughlin, Colette T. Dooley, Shainnel O. Eans Torrey Pines Institute For Molecular Studies, Radleigh Santos, Travis Lavoi, Adel Nefzi, Greg Welmaker, Marc A. Giulianotti, Lawrence Toll

Mathematics Faculty Articles

The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17 340 to 4 879 681 compounds) for analgesia directly in the mouse tail withdrawal model. The “all X” mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using …


Estimated Probability Of Becoming Alcohol Dependent: Extending A Multiparametric Approach, Olga A. Vsevolozhskaya, James C. Anthony Dec 2015

Estimated Probability Of Becoming Alcohol Dependent: Extending A Multiparametric Approach, Olga A. Vsevolozhskaya, James C. Anthony

Biostatistics Presentations

Background: United States (US) epidemiological studies suggest that for every 5-8 who start drinking alcoholic beverages, at least one drinker will develop an alcohol dependence (AD) syndrome within the first 10 years after onset of drinking (Lopez-Quintero et al., 2011; Wagner & Anthony, 2002). Recently, we described a multiparametric functional analysis approach for new research to estimate these transition probabilities with a one-dimensional function (1D; Vsevolozhskaya & Anthony, 2015). Here, we demonstrate extension of this analysis to two-dimensional (2D) functions that combine information about number of recent drinking days and number of drinks on the typical drinking day.

Methods: Data …


High Prevalence And Genetic Heterogeneity Of Rodent-Borne Bartonella Species On Heixiazi Island, China, Dong-Mei Li, Yong Hou, Xiu-Ping Song, Ying-Qun Fu, Gui-Chang Li, Ming Li, Marina E. Eremeeva, Hai-Xia Wu, Bo Pang, Yu-Juan Yue, Ying Huang, Liang Lu, Jun Wang, Qi-Yong Liu Dec 2015

High Prevalence And Genetic Heterogeneity Of Rodent-Borne Bartonella Species On Heixiazi Island, China, Dong-Mei Li, Yong Hou, Xiu-Ping Song, Ying-Qun Fu, Gui-Chang Li, Ming Li, Marina E. Eremeeva, Hai-Xia Wu, Bo Pang, Yu-Juan Yue, Ying Huang, Liang Lu, Jun Wang, Qi-Yong Liu

Environmental Health Sciences Faculty Publications

We performed genetic analysis of Bartonella isolates from rodent populations from Heixiazi Island in northeast China. Animals were captured at four sites representing grassland and brushwood habitats in 2011 and examined for the prevalence and genetic diversity of Bartonella species, their relationship to their hosts, and geographic distribution. A high prevalence (57.7%) and a high diversity (14 unique genotypes which belonged to 8 clades) of Bartonella spp. were detected from 71 rodents comprising 5 species and 4 genera from 3 rodent families. Forty-one Bartonella isolates were recovered and identified, including B. taylorii, B. japonica, B. coopersplainsensis, B. grahamii, B. washoensis …


Sports Broadcasting News Analysis [Career Paper], Jefferson Sanders Dec 2015

Sports Broadcasting News Analysis [Career Paper], Jefferson Sanders

Undergraduate Research Award

No abstract provided.


How To Start A Movement: Ted Talk Annotated Resource List, Daulton Cowan Dec 2015

How To Start A Movement: Ted Talk Annotated Resource List, Daulton Cowan

Undergraduate Research Award

No abstract provided.


Nursing: The Career That Saves Lives [Career Paper], Maggie Flanagan Dec 2015

Nursing: The Career That Saves Lives [Career Paper], Maggie Flanagan

Undergraduate Research Award

No abstract provided.


Predictive Formula For Electron Range Over A Large Span Of Energy, Anne C. Starley Dec 2015

Predictive Formula For Electron Range Over A Large Span Of Energy, Anne C. Starley

Reports

A model developed by the Materials Research Group that calculates electron penetration range of some common materials, has been greatly expanded with the hope that such extensions will predict the range in other, perhaps, more interesting materials. Developments in this extended model aid in predicting the approximate penetration depth into diverse classes of materials for a broad range of energetic incident electrons (10 MeV, with better than 20% accuracy). The penetration depth—or range—of a material describes the maximum distance electrons can travel through a material, before losing all of its incident kinetic energy. This model has started to predict a …


Factors Impacting Transgender Patients’ Discomfort With Their Family Physicians: A Respondent-Driven Sampling Survey, Greta R. Bauer, Xuchen Zong, Ayden I. Scheim, Rebecca Hammond, Amardeep Thind Dec 2015

Factors Impacting Transgender Patients’ Discomfort With Their Family Physicians: A Respondent-Driven Sampling Survey, Greta R. Bauer, Xuchen Zong, Ayden I. Scheim, Rebecca Hammond, Amardeep Thind

Epidemiology and Biostatistics Publications

BACKGROUND: Representing approximately 0.5% of the population, transgender (trans) persons in Canada depend on family physicians for both general and transition-related care. However, physicians receive little to no training on this patient population, and trans patients are often profoundly uncomfortable and may avoid health care. This study examined factors associated with patient discomfort discussing trans health issues with a family physician in Ontario, Canada.

METHODS: 433 trans people age 16 and over were surveyed using respondent-driven sampling for the Trans PULSE Project; 356 had a family physician. Weighted logistic regression models were fit to produce prevalence risk ratios (PRRs) via …


Investigating The Role Of The Host Multidrug Resistance Associated Protein Transporter Family In Burkholderia Cepacia Complex Pathogenicity Using A Caenorhabditis Elegans Infection Model, Pietro Tedesco, Marco Visone, Ermenegilda Parrilli, Maria Luisa Tutino, Elena Perrin, Isabel Maida, Renato Fani, Francesco Ballestriero, Radleigh Santos, Clemencia Pinilla, Elia Di Schiavi, George Tegos, Donatella De Pascale Nov 2015

Investigating The Role Of The Host Multidrug Resistance Associated Protein Transporter Family In Burkholderia Cepacia Complex Pathogenicity Using A Caenorhabditis Elegans Infection Model, Pietro Tedesco, Marco Visone, Ermenegilda Parrilli, Maria Luisa Tutino, Elena Perrin, Isabel Maida, Renato Fani, Francesco Ballestriero, Radleigh Santos, Clemencia Pinilla, Elia Di Schiavi, George Tegos, Donatella De Pascale

Mathematics Faculty Articles

This study investigated the relationship between host efflux system of the non-vertebrate nematode Caenorhabditis elegans and Burkholderia cepacia complex (Bcc) strain virulence. This is the first comprehensive effort to profile host-transporters within the context of Bcc infection. With this aim, two different toxicity tests were performed: a slow killing assay that monitors mortality of the host by intestinal colonization and a fast killing assay that assesses production of toxins. A Virulence Ranking scheme was defined, that expressed the toxicity of the Bcc panel members, based on the percentage of surviving worms. According to this ranking the 18 Bcc strains were …


Monitoring For Adverse Events Post Marketing Approval Of Drugs, Karl E. Peace, Macaulay Okwuokenye Nov 2015

Monitoring For Adverse Events Post Marketing Approval Of Drugs, Karl E. Peace, Macaulay Okwuokenye

Biostatistics Faculty Publications

This brief communication provides information to those developing monitoring plans for serious adverse events (SAE’s) following regulatory approval of a new drug. In addition, we (1) illustrate how many patients would need to be treated in order to have high confidence of seeing at least 1 pre-specified SAE, (2) show that absence of proof of a SAE is not proof of absence of that SAE, and (3) identify statistical methodology that could be used for formal statistical monitoring of SAE’s.


Science Undergraduate Research Conference 2015 Booklet, Dublin Institute Of Technology, Institute Of Technology, Tallaght, Institute Of Technology, Blanchardstown Nov 2015

Science Undergraduate Research Conference 2015 Booklet, Dublin Institute Of Technology, Institute Of Technology, Tallaght, Institute Of Technology, Blanchardstown

Group Reports

Dublin Institute of Technology (DIT), IT Tallaght and IT Blanchardstown hosted the Science Undergraduate Research Conference (SURC 2015) on 13th November 2015 in DIT's Grangegorman Campus. 25 students from DIT, IT Tallaght and IT Blanchardstown who completed an undergraduate research project in a Scientific discipline in the academic year 2014-15 presented at this conference.

The aims of the conference were to:

  1. Provide current students with an opportunity to gain an understanding of the work which has been undertaken by recent graduates, and the career opportunities that exist for graduates in Scientific disciplines.
  2. Provide recent graduates with an opportunity to gain …


Organometallic Rhenium Dyes For Nitric Oxide Detection And Imaging, Lissette I. Lozano-Lewis Nov 2015

Organometallic Rhenium Dyes For Nitric Oxide Detection And Imaging, Lissette I. Lozano-Lewis

FIU Electronic Theses and Dissertations

The importance of sensing Nitric Oxide (NO) in physiology and medicine has led us to explore the reactivity of NO with organometallic Re dyes. Rhenium complexes were synthesized with the ability to react with NO and sense it under physiological conditions. Fluorescent 1,10-phenantroline complexes (phen)Re(PPh3)(CO)2OSO2CF3 (1) and (phen)Re(CH3CN)(CO)2OSO2CF3 (3) can sense NO in the range of 10 - 150 mM showing a decrease in fluorescence response at 514 nm and 532 nm respectively, upon NO-donor addition (lexc = 360 nm). (phen)Re(THF)(CO)2OSO2CF …


Nested Partially-Latent, Class Models For Dependent Binary Data, Estimating Disease Etiology, Zhenke Wu, Maria Deloria-Knoll, Scott L. Zeger Nov 2015

Nested Partially-Latent, Class Models For Dependent Binary Data, Estimating Disease Etiology, Zhenke Wu, Maria Deloria-Knoll, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

The Pneumonia Etiology Research for Child Health (PERCH) study seeks to use modern measurement technology to infer the causes of pneumonia for which gold-standard evidence is unavailable. The paper describes a latent variable model designed to infer from case-control data the etiology distribution for the population of cases, and for an individual case given his or her measurements. We assume each observation is drawn from a mixture model for which each component represents one cause or disease class. The model addresses a major limitation of the traditional latent class approach by taking account of residual dependence among multivariate binary outcome …


Viral Infection Causes A Shift In The Self Peptide Repertoire Presented By Human Mhc Class I Molecules, Charles T. Spencer, Jelena S. Bezbradica, Mireya G. Ramos, Chenoa D. Arico, Stephanie B. Conant, Pavlo Gilchuk, Jennifer J. Gray, Mu Zheng, Xinnan Niu, William Hildebrand, Andrew J. Link, Sebastian Joyce Nov 2015

Viral Infection Causes A Shift In The Self Peptide Repertoire Presented By Human Mhc Class I Molecules, Charles T. Spencer, Jelena S. Bezbradica, Mireya G. Ramos, Chenoa D. Arico, Stephanie B. Conant, Pavlo Gilchuk, Jennifer J. Gray, Mu Zheng, Xinnan Niu, William Hildebrand, Andrew J. Link, Sebastian Joyce

Chemistry Faculty Research

Purpose

MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism.

Experimental design

The self peptide repertoire presented by HLA-A*01;01, HLA-A*02;01, HLA-B*07;02, HLA-B*35;01, and HLA-B*45;01 (where HLA is human leukocyte antigen) was determined by tandem MS before and after vaccinia virus infection.

Results

We observed a profound alteration in the self …


Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo Nov 2015

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …


Partial Covariance Based Functional Connectivity Computation Using Ledoit-Wolf Covariance Regularization, Matthew R. Brier, Anish Mitra, John E. Mccarthy, Beau M. Ances, Abraham Z. Snyder Nov 2015

Partial Covariance Based Functional Connectivity Computation Using Ledoit-Wolf Covariance Regularization, Matthew R. Brier, Anish Mitra, John E. Mccarthy, Beau M. Ances, Abraham Z. Snyder

Mathematics Faculty Publications

Highlights •We use the well characterized matrix regularization technique described by Ledoit and Wolf to calculate high dimensional partial correlations in fMRI data. •Using this approach we demonstrate that partial correlations reveal RSN structure suggesting that RSNs are defined by widely and uniquely shared variance. •Partial correlation functional connectivity is sensitive to changes in brain state indicating that they contain functional information. Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a …


Identification And Survival Outcomes Of A Cohort Of Patients With Cancer Of Unknown Primary In Ontario, Canada., Chong S Kim, Malek B Hannouf, Sisira Sarma, George B Rodrigues, Peter K Rogan, Salaheddin M Mahmud, Eric Winquist, Muriel Brackstone, Gregory S Zaric Nov 2015

Identification And Survival Outcomes Of A Cohort Of Patients With Cancer Of Unknown Primary In Ontario, Canada., Chong S Kim, Malek B Hannouf, Sisira Sarma, George B Rodrigues, Peter K Rogan, Salaheddin M Mahmud, Eric Winquist, Muriel Brackstone, Gregory S Zaric

Epidemiology and Biostatistics Publications

BACKGROUND: Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS).

MATERIAL AND METHODS: We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. …


Security And Privacy Of Electronic Health Information Systems: Editorial, Elisa Bertino, Robert H. Deng, Xinyi Huang, Jianying Zhou Nov 2015

Security And Privacy Of Electronic Health Information Systems: Editorial, Elisa Bertino, Robert H. Deng, Xinyi Huang, Jianying Zhou

Research Collection School Of Computing and Information Systems

Digital technologies have dramatically transformed our daily lives by bringing countless conveniences and benefits. As an evolving concept, electronic health information has become the focus of attention in both academia and industry. By leveraging modern digital technologies like the internet and the cloud, electronic health information systems will be a key enabling technology in improving the quality and convenience of patient care, encouraging patient participation in their care, reducing medical errors, improving practice efficiencies, and saving time and cost. The complexity of electronic health information systems, however, raises several new security and privacy issues. It is thus critical to investigate …


Local And Distributed Pib Accumulation Associated With Development Of Preclinical Alzheimer's Disease, Matthew R. Brier, John E. Mccarthy, Tammie L.S. Benzinger, Ari Stern, Yi Su, Karl A. Friedrichsen, John C. Morris, Beau M. Ances, Andrei G. Vlassenko Oct 2015

Local And Distributed Pib Accumulation Associated With Development Of Preclinical Alzheimer's Disease, Matthew R. Brier, John E. Mccarthy, Tammie L.S. Benzinger, Ari Stern, Yi Su, Karl A. Friedrichsen, John C. Morris, Beau M. Ances, Andrei G. Vlassenko

Mathematics Faculty Publications

Amyloid-beta plaques are a hallmark of Alzheimer's disease (AD) that can be assessed by amyloid imaging (e.g., Pittsburgh B compound [PiB]) and summarized as a scalar value. Summary values may have clinical utility but are an average over many regions of interest, potentially obscuring important topography. This study investigates the longitudinal evolution of amyloid topographies in cognitively normal older adults who had normal (N = 131) or abnormal (N = 26) PiB scans at baseline. At 3 years follow-up, 16 participants with a previously normal PiB scan had conversion to PiB scans consistent with preclinical AD. We investigated the multivariate …


'At-Risk' Places: Inequaties In The Distribution Of Environmental Stressors And Prescription Rates Of Mental Health Medications In Glasgow, Scotland, Juliana A. Maantay, Andrew Maroko Oct 2015

'At-Risk' Places: Inequaties In The Distribution Of Environmental Stressors And Prescription Rates Of Mental Health Medications In Glasgow, Scotland, Juliana A. Maantay, Andrew Maroko

Publications and Research

Using geospatial analytical methods, this study examines the association between one aspect of the built environment, namely, the concentration of vacant and derelict land (VDL), and the prevalence of mental health disorders (using the proxy variable of mental health medication prescription rates) in Glasgow, Scotland. This study builds on our previous research, which demonstrated the spatial correspondence between the locations of VDL in Glasgow and several physical health outcomes. Numerous studies of other locales have found similar correspondence between different elements of the built environment and various health outcomes. This is the first study of its kind to look at …


Integrated Bioinformatics, Environmental Epidemiologic And Genomic Approaches To Identify Environmental And Molecular Links Between Endometriosis And Breast Cancer, Deodutta Roy, Marisa L. Morgan, Changwon Yoo, Alok Deoraj, Sandhya Roy, Vijay Kumar Yadav, Mohannad Garoub, Hamza Assaggaf, Mayur Doke Oct 2015

Integrated Bioinformatics, Environmental Epidemiologic And Genomic Approaches To Identify Environmental And Molecular Links Between Endometriosis And Breast Cancer, Deodutta Roy, Marisa L. Morgan, Changwon Yoo, Alok Deoraj, Sandhya Roy, Vijay Kumar Yadav, Mohannad Garoub, Hamza Assaggaf, Mayur Doke

Department of Biostatistics Faculty Publications

We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by …


Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter Oct 2015

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …


Proper Orthogonal Decomposition Methods For The Analysis Of Real-Time Data: Exploring Peak Clustering In A Secondhand Smoke Exposure Intervention, Vincent Berardi, R. Carretero-González, N. E. Klepeis, A. Palacios, J. Belletierre, S. Hughes, S. Obayashi, M. F. Hovell Oct 2015

Proper Orthogonal Decomposition Methods For The Analysis Of Real-Time Data: Exploring Peak Clustering In A Secondhand Smoke Exposure Intervention, Vincent Berardi, R. Carretero-González, N. E. Klepeis, A. Palacios, J. Belletierre, S. Hughes, S. Obayashi, M. F. Hovell

Psychology Faculty Articles and Research

This work explores a method for classifying peaks appearing within a data-intensive time-series. We summarize a case study from a clinical trial aimed at reducing secondhand smoke exposure via the installation of air particle monitors in households. Proper orthogonal decomposition (POD) in conjunction with a k-means clustering algorithm assigns each data peak to one of two clusters. Aversive feedback from the monitors increased the proportion of short-duration, attenuated peaks from 38.8% to 96.6%. For each cluster, a distribution of parameters from a physics-based model of airborne particles is estimated. Peaks generated from these distributions are correctly identified by POD/clustering …


Using Water–Solvent Systems To Estimate In Vivo Blood–Tissue Partition Coefficients, Andrew Lang, Caitlin E. Derricott Oct 2015

Using Water–Solvent Systems To Estimate In Vivo Blood–Tissue Partition Coefficients, Andrew Lang, Caitlin E. Derricott

College of Science and Engineering Faculty Research and Scholarship

Background: Blood–tissue partition coefficients indicate how a chemical will distribute throughout the body and are an important part of any pharmacokinetic study. They can be used to assess potential toxicological effects from exposure to chemicals and the efficacy of potential novel drugs designed to target certain organs or the central nervous system. In vivo measurement of blood–tissue partition coefficients is often complicated, time-consuming, and relatively expensive, so developing in vitro systems that approximate in vivo ones is desirable. We have determined such systems for tissues such as brain, muscle, liver, lung, kidney, heart, skin, and fat. Results: Several good (p < 0.05) blood–tissue partition coefficient models were developed using a single water– solvent system. These include blood–brain, blood–lung, blood–heart, blood–fat, blood–skin, water–skin, and skin permeation. Many of these partition coefficients have multiple water–solvent systems that can be used as models. Several solvents—methylcyclohexane, 1,9-decadiene, and 2,2,2-trifluoroethanol—were common to multiple models and thus a single measurement can be used to estimate multiple blood–tissue partition coefficients. A few blood–tissue systems require a combination of two water–solvent partition coefficient measurements to model well (p < 0.01), namely: blood–muscle: chloroform and dibutyl ether, blood–liver: N-methyl-2-piperidone and ethanol/water (60:40) volume, and blood–kidney: DMSO and ethanol/water (20:80) volume. Conclusion: In vivo blood–tissue partition coefficients can be easily estimated through water–solvent partition coefficient measurements.


Anti-Tb And Antibacterial Activities Of Natural Products Extracts, Douglas Armstrong, Nathan Krause, Drew Frey Oct 2015

Anti-Tb And Antibacterial Activities Of Natural Products Extracts, Douglas Armstrong, Nathan Krause, Drew Frey

Faculty Scholarship – Chemistry

Samples of numerous plant species were received from the southwestern part of the USA from Richard Spjut, and plant samples were collected here in Illinois. All were extracted with typical solvents, giving crude residues, some of which were subjected to counter-current or flash chromatographic methods. Some of the crude extracts and chromatographic fractions had anti-tuberculosis and/or antibacterial activity.

In a general way, bioactive natural products are dealt with very well by Liang & Fang, 2006. More specifically, the southwestern part of the United States has a large variety of indigenous plants, many of which have not been investigated for their …


Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman Oct 2015

Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman

Publications and Research

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic …


Dynapenic Obesity And The Effect On Long-Term Physical Function And Quality Of Life: Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Dawna Pidgeon, Stephen J. Bartels Oct 2015

Dynapenic Obesity And The Effect On Long-Term Physical Function And Quality Of Life: Data From The Osteoarthritis Initiative, John A. Batsis, Alicia J. Zbehlik, Dawna Pidgeon, Stephen J. Bartels

Dartmouth Scholarship

Obesity is associated with functional impairment, institutionalization, and increased mortality risk in elders. Dynapenia is defined as reduced muscle strength and is a known independent predictor of adverse events and disability. The synergy between dynapenia and obesity leads to worse outcomes than either independently. We identified the impact of dynapenic obesity in a cohort at risk for and with knee osteoarthritis on function.


Stress Granules Modulate Syk To Cause Microglial Cell Dysfunction In Alzheimer's Disease, Soumira Ghosh, Robert Geahlen Oct 2015

Stress Granules Modulate Syk To Cause Microglial Cell Dysfunction In Alzheimer's Disease, Soumira Ghosh, Robert Geahlen

Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Microglial cells in the brains of Alzheimer's patients are known to be recruited to amyloid-beta (Aβ) plaques where they exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. In this study, we show that microglia stressed by exposure to sodium arsenite or Aβ(1–42) peptides or fibrils form ex- tensive stress granules (SGs) to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of SGs, is active within the resulting SGs and stimulates the production of reactive oxygen and nitrogen species that are toxic to neuronal cells. This sequestration of SYK inhibits the ability of microglial …


Comparison Of Fecal Microbiota In Children With Autism Spectrum Disorders And Neurotypical Siblings In The Simons Simplex Collection, Joshua S. Son, Ling J. Zheng, Leahana M. Rowehl, Ellen Li, Xinyu Tian, Yuanhao Zhang, Wei Zhu, Leighann Litcher-Kelly, Kenneth D. Gadow, Grace Gathungu, Charles E. Robertson, Diana Ir, Daniel N. Frank Oct 2015

Comparison Of Fecal Microbiota In Children With Autism Spectrum Disorders And Neurotypical Siblings In The Simons Simplex Collection, Joshua S. Son, Ling J. Zheng, Leahana M. Rowehl, Ellen Li, Xinyu Tian, Yuanhao Zhang, Wei Zhu, Leighann Litcher-Kelly, Kenneth D. Gadow, Grace Gathungu, Charles E. Robertson, Diana Ir, Daniel N. Frank

Department of Applied Mathematics & Statistics Faculty Publications

In order to assess potential associations between autism spectrum disorder (ASD) phenotype, functional GI disorders and fecal microbiota, we recruited simplex families, which had only a single ASD proband and neurotypical (NT) siblings, through the Simons Simplex Community at the Interactive Autism Network (SSC@IAN). Fecal samples and metadata related to functional GI disorders and diet were collected from ASD probands and NT siblings of ASD probands (age 7–14). Functional gastrointestinal disorders (FGID) were assessed using the parent-completed ROME III questionnaire for pediatric FGIDs, and problem behaviors were assessed using the Child Behavior Check List (CBCL). Targeted quantitative polymerase chain reaction …