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  1. AU="Whalen, Kevin"
  2. AU="Jengić, Vesna Sendula"
  3. AU=Charidimou Andreas
  4. AU="Mazen Ferwana"
  5. AU="Murat Akbas"
  6. AU="Fini, Nicola"
  7. AU="Moroni, Anna"
  8. AU=Kreger Bridget T.
  9. AU="Woods, Angela L"
  10. AU=Iba Toshiaki
  11. AU="Akberova, N I"
  12. AU="Bolouki Moghaddam, Farzaneh"
  13. AU="Rajeshkannan, Nadarajah"
  14. AU="Noda, Judith"
  15. AU=Loucks Catrina M.
  16. AU="Lachérade, J-C"
  17. AU=Jalali Subhadra AU=Jalali Subhadra
  18. AU="Yang, Yung"
  19. AU="Belt, Brian"
  20. AU="Beckley, Akinpelumi A"
  21. AU="Adams, Tempe"
  22. AU=Wahidi Momen M
  23. AU="Pardis C. Sabeti"
  24. AU=Arkowitz Robert A
  25. AU="Sempoux, Christine"
  26. AU="Selebatso, Moses"
  27. AU=Sountoulides Petros
  28. AU="Huachun Zou"
  29. AU=SHENG Nan AU=SHENG Nan
  30. AU="Gascon, Pierre"
  31. AU="Hoa Phong, Pham Huu Thien"
  32. AU="Guiyan Ni"

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  1. Artikel: Finding the Balance

    Whalen, Kevin

    American behavioral scientist. , v. 58, no. 1

    Student Voices and Cultural Loss at Sherman Institute

    2014  

    Abstract: Since mid-1990s, scholars of Indian education have placed increasing emphasis on indigenous approaches to federal Indian boarding schools during the early 20th century. Where earlier studies emphasized the design and operation of boarding schools, more ... ...

    Abstract Since mid-1990s, scholars of Indian education have placed increasing emphasis on indigenous approaches to federal Indian boarding schools during the early 20th century. Where earlier studies emphasized the design and operation of boarding schools, more recent literature often examines how Native students, families, and communities sometimes used the schools to access employment, offset financial hardship, and gain new skills and perspectives. To some, scholarly emphasis on “the brighter side of boarding schools” covers over the hardship and loss brought about by institutions created to eradicate Native American cultures and identities. In this article, I address a central question: How can scholars of Indian education illuminate Native approaches to boarding schools without underplaying the tremendous cultural loss they inflicted on indigenous communities? Drawing on the expansive secondary literature on federal Indian education and primary source documents from Sherman Institute, a federal Indian boarding school in Riverside, California, I argue that studies of Indian education can benefit from deeper consideration of the concept of “cultural genocide” and careful attention to Native voices of the past and present.
    Schlagwörter American Indians ; employment ; schools ; students ; California
    Sprache Englisch
    Erscheinungsverlauf 2014-01
    Umfang p. 124-144.
    Erscheinungsort SAGE Publications
    Dokumenttyp Artikel
    ISSN 1552-3381
    DOI 10.1177/0002764213495026
    Datenquelle NAL Katalog (AGRICOLA)

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  2. Artikel: A centralized approach to tandem mass spectrometry method development for high-throughput ADME screening.

    Whalen, Kevin / Gobey, Jason / Janiszewski, John

    Rapid communications in mass spectrometry : RCM

    2006  Band 20, Heft 10, Seite(n) 1497–1503

    Abstract: A centralized approach to acquisition and dissemination of tandem mass spectrometry (MS/MS) conditions within an ADME-screening bioanalytical mass spectrometry group has been developed. The method development process uses two automated software products ( ...

    Abstract A centralized approach to acquisition and dissemination of tandem mass spectrometry (MS/MS) conditions within an ADME-screening bioanalytical mass spectrometry group has been developed. The method development process uses two automated software products (Autoscan and Automaton) specifically designed for mass spectrometers manufactured by MDS Sciex. Both provide the ability to quickly determine selected reaction monitoring (SRM) transitions for hundreds of compounds per day. In addition, Autoscan determines optimal polarity and collision energy (CE). Automaton also determines the optimal declustering potential (DP) as well as the CE. The resulting optimized conditions are loaded into a central database for access by LC/MS/MS bioanalysis workstations in the group. The effect of DP and CE on the sensitivity was investigated. Optimization of DP improved signal response about 27% on average. For approximately 10% of compounds, signal enhancement was greater than 50% compared to the generic setting. A generic setting of DP = 25 V can be used for the majority of ADME-screening applications. Optimization of CE can have a much larger impact on signal intensity and a minimum of three CE settings should be tested. We have determined that CE values of 1, 30 and 45 V provide adequate coverage for most small molecule drug discovery analytes.
    Mesh-Begriff(e) Chromatography, Liquid ; Databases, Factual ; Drug Design ; Drug Evaluation, Preclinical/methods ; Drug-Related Side Effects and Adverse Reactions ; Pharmaceutical Preparations/metabolism ; Software ; Tandem Mass Spectrometry/methods
    Chemische Substanzen Pharmaceutical Preparations
    Sprache Englisch
    Erscheinungsdatum 2006
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 58731-x
    ISSN 1097-0231 ; 0951-4198
    ISSN (online) 1097-0231
    ISSN 0951-4198
    DOI 10.1002/rcm.2469
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Effect of maturation on parr growth and smolt recruitment of Atlantic salmon

    Whalen, Kevin G / Donna L Parrish

    Canadian journal of fisheries and aquatic sciences. 1999 Jan. 01, v. 56, no. 1

    1999  

    Abstract: We determined the effect of maturation on parr growth and smolt recruitment of Atlantic salmon (Salmo salar) stocked in Vermont tributaries of the Connecticut River. Both among and within tributaries, mature parr ranged between 28 and 52% of the age-1 ... ...

    Abstract We determined the effect of maturation on parr growth and smolt recruitment of Atlantic salmon (Salmo salar) stocked in Vermont tributaries of the Connecticut River. Both among and within tributaries, mature parr ranged between 28 and 52% of the age-1 parr collected and up to 67% of the age-2 parr collected. Percent age-1 parr maturing in October-November was positively related to mean length the preceding June. In October-November, immature age-1 parr were greater in mean length than age-1 mature parr. Data from parr individually tagged in June and recaptured in October showed immature parr exhibited twofold greater individual growth than maturing parr. Smolt recruitment was highly dependent upon state of maturity the preceding fall; fewer individuals that matured as parr recruited to smolt compared with parr remaining immature. Our study shows, over a broad spatial scale, that variation in incidence of maturation is largely explained by parr size among tributaries and river reaches and, furthermore, empirically demonstrates a direct negative effect of maturation on parr growth and recruitment to smolt. Thus, parr maturation is an important consideration for the enhancement and (or) restoration of Atlantic salmon populations via stream stocking programs.
    Schlagwörter adverse effects ; parr ; rivers ; Salmo salar ; smolts ; streams ; Connecticut River ; Vermont
    Sprache Englisch
    Erscheinungsverlauf 1999-0101
    Umfang p. 79-86.
    Erscheinungsort NRC Research Press
    Dokumenttyp Artikel
    ZDB-ID 1473089-3
    ISSN 1205-7533 ; 0706-652X
    ISSN (online) 1205-7533
    ISSN 0706-652X
    DOI 10.1139/f98-154
    Datenquelle NAL Katalog (AGRICOLA)

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  4. Artikel ; Online: Development of a high-speed, multiplexed sample-delivery instrument for LC-MS/MS bioanalysis.

    Janiszewski, John / Schneider, Richard / Kapinos, Brendon / West, Mike / Funk, Carrie / Federico, James / Umland, John / Piotrowski, Mary / Mitchell, Walter / Zhang, Hui / Zelesky, Veronica / Gobey, Jason / Whalen, Kevin / Liston, Theodore / Troutman, Matthew

    Bioanalysis

    2012  Band 4, Heft 9, Seite(n) 1039–1056

    Abstract: Background: The number of new chemical entities and types of in vitro and in vivo samples that require bioanalysis in drug discovery is large and diverse. In addition, method development time is limited as data turnaround is the highest priority. These ... ...

    Abstract Background: The number of new chemical entities and types of in vitro and in vivo samples that require bioanalysis in drug discovery is large and diverse. In addition, method development time is limited as data turnaround is the highest priority. These circumstances require that a well-defined set of bioanalysis options be available in short timeframes to triage samples for analysis.
    Method: The Apricot Designs Dual Arm (ADDA) instrument is an LC-MS/MS sample delivery system that features a flexible hardware design coupled with software automation to enhance throughput in LC-MS/MS bioanalysis drug discovery. The instrument can perform high-throughput LC-MS/MS (8-10 s/sample) for screening and in vitro bioanalysis, as well as multiplexed LC for traditional gradient or isocratic LC approaches. The instrument control software is designed to integrate with DiscoveryQuant™ software (AB Sciex) and a global database of MS/MS conditions.
    Conclusion: Development of the sample delivery platform and its application in high-throughput and gradient LC will be described.
    Mesh-Begriff(e) Chromatography, High Pressure Liquid/instrumentation ; Chromatography, High Pressure Liquid/methods ; Drug Interactions ; High-Throughput Screening Assays ; Mass Spectrometry/instrumentation ; Mass Spectrometry/methods ; Pharmaceutical Preparations/analysis
    Chemische Substanzen Pharmaceutical Preparations
    Sprache Englisch
    Erscheinungsdatum 2012-05
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 1757-6199
    ISSN (online) 1757-6199
    DOI 10.4155/bio.12.87
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Differential modulation of cytochrome P450 activity and the effect of 1-aminobenzotriazole on hepatic transport in sandwich-cultured human hepatocytes.

    Kimoto, Emi / Walsky, Robert / Zhang, Hui / Bi, Yi-an / Whalen, Kevin M / Yang, Young-Sun / Linder, Collette / Xiao, Yongling / Iseki, Ken / Fenner, Katherine S / El-Kattan, Ayman F / Lai, Yurong

    Drug metabolism and disposition: the biological fate of chemicals

    2012  Band 40, Heft 2, Seite(n) 407–411

    Abstract: Sandwich-cultured human hepatocytes (SCHH) have been widely used for in vitro assessments of biliary clearance. However, the modulation of metabolism enzymes has not been fully evaluated in this system. The present study was therefore undertaken to ... ...

    Abstract Sandwich-cultured human hepatocytes (SCHH) have been widely used for in vitro assessments of biliary clearance. However, the modulation of metabolism enzymes has not been fully evaluated in this system. The present study was therefore undertaken to determine the activity of cytochrome P450 (P450) 1A2, 2C8, 2C9, 2C19, 2D6, and 3A and to evaluate the impact of 1-aminobenzotriazole (ABT) on hepatic uptake and biliary excretion in SCHH. The SCHH maintained integrity and viability as determined by lactate dehydrogenase release and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assays conducted over the culture period. Although all assessed P450 activity decreased in day 2 SCHH, the extent of the decrease and the subsequent rebound in activity varied across the different isoforms. Day 5 CYP1A2 activity was approximately 2.5-fold higher than day 1 activity, whereas the CYP3A and CYP2C9 activities were 90 and 60% of the day 1 levels, respectively. In contrast, the initial CYP2C8, CYP2C19, and CYP2D6 activity losses did not rebound over the 5-day culture period. Furthermore, ABT was not found to have an effect, whether directly or indirectly as a P450 inactivator, with respect to the hepatic transport of rosuvastatin, atrovastatin, and midazolam in SCHH. Taken together, these results suggest that the SCHH model is a reliable tool to characterize hepatic uptake and biliary excretion. Due to the differential modulation of P450 activity, SCHH may not be considered a suitable tool for metabolic stability assessments with compounds predominantly cleared by certain P450 enzymes.
    Mesh-Begriff(e) Anti-Anxiety Agents/metabolism ; Anticholesteremic Agents/metabolism ; Atorvastatin Calcium ; Bile/metabolism ; Biological Transport/drug effects ; Cell Survival ; Cells, Cultured ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System/metabolism ; Enzyme Inhibitors/pharmacology ; Fluorobenzenes/metabolism ; Hepatocytes/drug effects ; Hepatocytes/enzymology ; Hepatocytes/metabolism ; Hepatocytes/secretion ; Heptanoic Acids/metabolism ; Humans ; Isoenzymes/antagonists & inhibitors ; Isoenzymes/metabolism ; Midazolam/metabolism ; Models, Biological ; Pyrimidines/metabolism ; Pyrroles/metabolism ; Rosuvastatin Calcium ; Sulfonamides/metabolism ; Time Factors ; Triazoles/pharmacology
    Chemische Substanzen Anti-Anxiety Agents ; Anticholesteremic Agents ; Cytochrome P-450 Enzyme Inhibitors ; Enzyme Inhibitors ; Fluorobenzenes ; Heptanoic Acids ; Isoenzymes ; Pyrimidines ; Pyrroles ; Sulfonamides ; Triazoles ; 1-aminobenzotriazole (1614-12-6) ; Atorvastatin Calcium (48A5M73Z4Q) ; Rosuvastatin Calcium (83MVU38M7Q) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Midazolam (R60L0SM5BC)
    Sprache Englisch
    Erscheinungsdatum 2012-02
    Erscheinungsland United States
    Dokumenttyp Evaluation Studies ; Journal Article
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.111.039297
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: In vitro evaluation of hepatic transporter-mediated clinical drug-drug interactions: hepatocyte model optimization and retrospective investigation.

    Bi, Yi-An / Kimoto, Emi / Sevidal, Samantha / Jones, Hannah M / Barton, Hugh A / Kempshall, Sarah / Whalen, Kevin M / Zhang, Hui / Ji, Chengjie / Fenner, Katherine S / El-Kattan, Ayman F / Lai, Yurong

    Drug metabolism and disposition: the biological fate of chemicals

    2012  Band 40, Heft 6, Seite(n) 1085–1092

    Abstract: To assess the feasibility of using sandwich-cultured human hepatocytes (SCHHs) as a model to characterize transport kinetics for in vivo pharmacokinetic prediction, the expression of organic anion-transporting polypeptide (OATP) proteins in SCHHs, along ... ...

    Abstract To assess the feasibility of using sandwich-cultured human hepatocytes (SCHHs) as a model to characterize transport kinetics for in vivo pharmacokinetic prediction, the expression of organic anion-transporting polypeptide (OATP) proteins in SCHHs, along with biliary efflux transporters, was confirmed quantitatively by liquid chromatography-tandem mass spectrometry. Rifamycin SV (Rif SV), which was shown to completely block the function of OATP transporters, was selected as an inhibitor to assess the initial rates of active uptake. The optimized SCHH model was applied in a retrospective investigation of compounds with known clinically significant OATP-mediated uptake and was applied further to explore drug-drug interactions (DDIs). Greater than 50% inhibition of active uptake by Rif SV was found to be associated with clinically significant OATP-mediated DDIs. We propose that the in vitro active uptake value therefore could serve as a cutoff for class 3 and 4 compounds of the Biopharmaceutics Drug Disposition Classification System, which could be integrated into the International Transporter Consortium decision tree recommendations to trigger clinical evaluations for potential DDI risks. Furthermore, the kinetics of in vitro hepatobiliary transport obtained from SCHHs, along with protein expression scaling factors, offer an opportunity to predict complex in vivo processes using mathematical models, such as physiologically based pharmacokinetics models.
    Mesh-Begriff(e) Cells, Cultured ; Drug Evaluation, Preclinical/methods ; Drug Interactions/physiology ; Hepatocytes/metabolism ; Humans ; Organic Anion Transporters/metabolism ; Pharmaceutical Preparations/metabolism ; Retrospective Studies
    Chemische Substanzen Organic Anion Transporters ; Pharmaceutical Preparations
    Sprache Englisch
    Erscheinungsdatum 2012-06
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.111.043489
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1.

    Varma, Manthena V / Rotter, Charles J / Chupka, Jonathan / Whalen, Kevin M / Duignan, David B / Feng, Bo / Litchfield, John / Goosen, Theunis C / El-Kattan, Ayman F

    Molecular pharmaceutics

    2011  Band 8, Heft 4, Seite(n) 1303–1313

    Abstract: The human organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) is ubiquitously expressed and may play an important role in the disposition of xenobiotics. The present study aimed to examine the role of OATP2B1 in the intestinal absorption and ... ...

    Abstract The human organic anion transporting polypeptide 2B1 (OATP2B1, SLCO2B1) is ubiquitously expressed and may play an important role in the disposition of xenobiotics. The present study aimed to examine the role of OATP2B1 in the intestinal absorption and tissue uptake of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors (statins). We first investigated the functional affinity of statins to the transporter as a function of extracellular pH, using OATP2B1-transfeced HEK293 cells. The results indicate that OATP2B1-mediated transport is significant for rosuvastatin, fluvastatin and atorvastatin, at neutral pH. However, OATP2B1 showed broader substrate specificity as well as enhanced transporter activity at acidic pH. Furthermore, uptake at acidic pH was diminished in the presence of proton ionophore, suggesting proton gradient as the driving force for OATP2B1 activity. Notably, passive transport rates are predominant or comparable to active transport rates for statins, except for rosuvastatin and fluvastatin. Second, we studied the effect of OATP modulators on statin uptake. At pH 6.0, OATP2B1-mediated transport of atorvastatin and cerivastatin was not inhibitable, while rosuvastatin transport was inhibited by E-3-S, rifamycin SV and cyclosporine with IC(50) values of 19.7 ± 3.3 μM, 0.53 ± 0.2 μM and 2.2 ± 0.4 μM, respectively. Rifamycin SV inhibited OATP2B1-mediated transport of E-3-S and rosuvastatin with similar IC(50) values at pH 6.0 and 7.4, suggesting that the inhibitor affinity is not pH-dependent. Finally, we noted that OATP2B1-mediated transport of E-3-S, but not rosuvastatin, is pH sensitive in intestinal epithelial (Caco-2) cells. However, uptake of E-3-S and rosuvastatin by Caco-2 cells was diminished in the presence of proton ionophore. The present results indicate that OATP2B1 may be involved in the tissue uptake of rosuvastatin and fluvastatin, while OATP2B1 may play a significant role in the intestinal absorption of several statins due to their transporter affinity at acidic pH.
    Mesh-Begriff(e) Atorvastatin Calcium ; Caco-2 Cells ; Cell Line ; Chromatography, Liquid ; Estrone/analogs & derivatives ; Estrone/metabolism ; Fatty Acids, Monounsaturated/metabolism ; Fluorobenzenes/metabolism ; Heptanoic Acids/metabolism ; Humans ; Hydrogen-Ion Concentration ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism ; Indoles/metabolism ; Intestinal Absorption ; Organic Anion Transporters/genetics ; Organic Anion Transporters/metabolism ; Pyrimidines/metabolism ; Pyrroles/metabolism ; Rosuvastatin Calcium ; Sulfonamides/metabolism ; Tandem Mass Spectrometry
    Chemische Substanzen Fatty Acids, Monounsaturated ; Fluorobenzenes ; Heptanoic Acids ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Indoles ; Organic Anion Transporters ; Pyrimidines ; Pyrroles ; SLCO2B1 protein, human ; Sulfonamides ; Estrone (2DI9HA706A) ; Atorvastatin Calcium (48A5M73Z4Q) ; fluvastatin (4L066368AS) ; Rosuvastatin Calcium (83MVU38M7Q) ; estrone sulfate (QTL48N278K)
    Sprache Englisch
    Erscheinungsdatum 2011-08-01
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/mp200103h
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel: High throughput ADME screening: practical considerations, impact on the portfolio and enabler of in silico ADME models.

    Hop, Cornelis E C A / Cole, Mark J / Davidson, Ralph E / Duignan, David B / Federico, James / Janiszewski, John S / Jenkins, Kelly / Krueger, Suzanne / Lebowitz, Rebecca / Liston, Theodore E / Mitchell, Walter / Snyder, Mark / Steyn, Stefan J / Soglia, John R / Taylor, Christine / Troutman, Matt D / Umland, John / West, Michael / Whalen, Kevin M /
    Zelesky, Veronica / Zhao, Sabrina X

    Current drug metabolism

    2008  Band 9, Heft 9, Seite(n) 847–853

    Abstract: Evaluation and optimization of drug metabolism and pharmacokinetic data plays an important role in drug discovery and development and several reliable in vitro ADME models are available. Recently higher throughput in vitro ADME screening facilities have ... ...

    Abstract Evaluation and optimization of drug metabolism and pharmacokinetic data plays an important role in drug discovery and development and several reliable in vitro ADME models are available. Recently higher throughput in vitro ADME screening facilities have been established in order to be able to evaluate an appreciable fraction of synthesized compounds. The ADME screening process can be dissected in five distinct steps: (1) plate management of compounds in need of in vitro ADME data, (2) optimization of the MS/MS method for the compounds, (3) in vitro ADME experiments and sample clean up, (4) collection and reduction of the raw LC-MS/MS data and (5) archival of the processed ADME data. All steps will be described in detail and the value of the data on drug discovery projects will be discussed as well. Finally, in vitro ADME screening can generate large quantities of data obtained under identical conditions to allow building of reliable in silico models.
    Mesh-Begriff(e) Animals ; Computer Simulation ; Drug Evaluation, Preclinical/standards ; Drug Evaluation, Preclinical/statistics & numerical data ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Pharmaceutical Preparations/metabolism ; Pharmacokinetics ; Quality Control
    Chemische Substanzen Pharmaceutical Preparations
    Sprache Englisch
    Erscheinungsdatum 2008-10-17
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2064815-7
    ISSN 1875-5453 ; 1389-2002
    ISSN (online) 1875-5453
    ISSN 1389-2002
    DOI 10.2174/138920008786485092
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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