The Effects of Substrate Elastic Modulus on Neural Precursor Cell Behavior
The spinal cord has a limited capacity to self-repair. After injury, endogenous stem cells are activated and migrate, proliferate, and differentiate into glial cells. The absence of neuronal differentiation has been partly attributed to the interaction between the injured microenvironment and neural...
Gespeichert in:
| Veröffentlicht in: | Annals of biomedical engineering 2013-06, Vol.41 (6), p.1193-1207 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1207 |
|---|---|
| container_issue | 6 |
| container_start_page | 1193 |
| container_title | Annals of biomedical engineering |
| container_volume | 41 |
| creator | Previtera, Michelle L. Hui, Mason Verma, Devendra Shahin, Abdelhamid J. Schloss, Rene Langrana, Noshir A. |
| description | The spinal cord has a limited capacity to self-repair. After injury, endogenous stem cells are activated and migrate, proliferate, and differentiate into glial cells. The absence of neuronal differentiation has been partly attributed to the interaction between the injured microenvironment and neural stem cells. In order to improve post-injury neuronal differentiation and/or maturation potential, cell–cell and cell–biochemical interactions have been investigated. However, little is known about the role of stem cell–matrix interactions on stem cell-mediated repair. Here, we specifically examined the effects of matrix elasticity on stem cell-mediated repair in the spinal cord, since spinal cord injury results in drastic changes in parenchyma elasticity and viscosity. Spinal cord-derived neural precursor cells (NPCs) were grown on bis-acrylamide substrates with various rigidities. NPC growth, proliferation, and differentiation were examined and optimal in the range of normal spinal cord elasticity. In conclusion, limitations in NPC growth, proliferation, and neuronal differentiation were encountered when substrate elasticity was not within normal spinal cord tissue elasticity ranges. These studies elucidate the effect injury mediated mechanical changes may have on tissue repair by stem cells. Furthermore, this information can be applied to the development of future neuroregenerative biomaterials for spinal cord repair. |
| doi_str_mv | 10.1007/s10439-013-0765-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1352289967</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1347255127</sourcerecordid><originalsourceid>FETCH-LOGICAL-c405t-379031cdebea44758901bf428eafd94f701dd842e212b127035c1166c35e48c33</originalsourceid><addsrcrecordid>eNqNkU1LHEEQhhtJ0PXjB3gJA7nkMqaqP6ePZjFqMFFQz01PT01cmd3R7unA_nt7WQ0hEMipoeupt6p4GDtGOEEA8zkhSGFrQFGD0ape77AZKiNqqxv9js0ALNTaarnH9lN6BEBshNple1xIbq3mM_bt7oGqs76nMKVq7Kvb3KYp-ql8Dj5Ni1B9H7s85FJcVT8oRz9UN5FCjmmM1ZyGofpCD_7XYoyH7H3vh0RHr-8Bu_96dje_qK-uzy_np1d1kKCmWhgLAkNHLXkpjWosYNtL3pDvOyt7A9h1jeTEkbfIDQgVELUOQpFsghAH7NM29ymOz5nS5JaLFMomfkVjTg6F4rwp55n_QKXhSpUpBf34F_o45rgqh2woLYzgxhYKt1SIY0qRevcUF0sf1w7BbZy4rRNXnLiNE7cuPR9ek3O7pO53x5uEAvAtkEpp9ZPiH6P_mfoCUmmUsw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1346373279</pqid></control><display><type>article</type><title>The Effects of Substrate Elastic Modulus on Neural Precursor Cell Behavior</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Previtera, Michelle L. ; Hui, Mason ; Verma, Devendra ; Shahin, Abdelhamid J. ; Schloss, Rene ; Langrana, Noshir A.</creator><creatorcontrib>Previtera, Michelle L. ; Hui, Mason ; Verma, Devendra ; Shahin, Abdelhamid J. ; Schloss, Rene ; Langrana, Noshir A.</creatorcontrib><description>The spinal cord has a limited capacity to self-repair. After injury, endogenous stem cells are activated and migrate, proliferate, and differentiate into glial cells. The absence of neuronal differentiation has been partly attributed to the interaction between the injured microenvironment and neural stem cells. In order to improve post-injury neuronal differentiation and/or maturation potential, cell–cell and cell–biochemical interactions have been investigated. However, little is known about the role of stem cell–matrix interactions on stem cell-mediated repair. Here, we specifically examined the effects of matrix elasticity on stem cell-mediated repair in the spinal cord, since spinal cord injury results in drastic changes in parenchyma elasticity and viscosity. Spinal cord-derived neural precursor cells (NPCs) were grown on bis-acrylamide substrates with various rigidities. NPC growth, proliferation, and differentiation were examined and optimal in the range of normal spinal cord elasticity. In conclusion, limitations in NPC growth, proliferation, and neuronal differentiation were encountered when substrate elasticity was not within normal spinal cord tissue elasticity ranges. These studies elucidate the effect injury mediated mechanical changes may have on tissue repair by stem cells. Furthermore, this information can be applied to the development of future neuroregenerative biomaterials for spinal cord repair.</description><identifier>ISSN: 0090-6964</identifier><identifier>EISSN: 1573-9686</identifier><identifier>DOI: 10.1007/s10439-013-0765-y</identifier><identifier>PMID: 23429962</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Animals ; Biochemistry ; Biological and Medical Physics ; Biomaterials ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Biophysics ; Cell Adhesion ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Classical Mechanics ; Elastic Modulus ; Fibroblast Growth Factors - pharmacology ; Intermediate Filament Proteins - physiology ; Ki-67 Antigen - physiology ; Microtubule-Associated Proteins - physiology ; Nerve Tissue Proteins - physiology ; Nestin ; Neurons - cytology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord - cytology ; Spinal Cord - physiology ; Stem cells ; Stem Cells - cytology ; Stem Cells - drug effects ; Stem Cells - physiology</subject><ispartof>Annals of biomedical engineering, 2013-06, Vol.41 (6), p.1193-1207</ispartof><rights>Biomedical Engineering Society 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-379031cdebea44758901bf428eafd94f701dd842e212b127035c1166c35e48c33</citedby><cites>FETCH-LOGICAL-c405t-379031cdebea44758901bf428eafd94f701dd842e212b127035c1166c35e48c33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10439-013-0765-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10439-013-0765-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23429962$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Previtera, Michelle L.</creatorcontrib><creatorcontrib>Hui, Mason</creatorcontrib><creatorcontrib>Verma, Devendra</creatorcontrib><creatorcontrib>Shahin, Abdelhamid J.</creatorcontrib><creatorcontrib>Schloss, Rene</creatorcontrib><creatorcontrib>Langrana, Noshir A.</creatorcontrib><title>The Effects of Substrate Elastic Modulus on Neural Precursor Cell Behavior</title><title>Annals of biomedical engineering</title><addtitle>Ann Biomed Eng</addtitle><addtitle>Ann Biomed Eng</addtitle><description>The spinal cord has a limited capacity to self-repair. After injury, endogenous stem cells are activated and migrate, proliferate, and differentiate into glial cells. The absence of neuronal differentiation has been partly attributed to the interaction between the injured microenvironment and neural stem cells. In order to improve post-injury neuronal differentiation and/or maturation potential, cell–cell and cell–biochemical interactions have been investigated. However, little is known about the role of stem cell–matrix interactions on stem cell-mediated repair. Here, we specifically examined the effects of matrix elasticity on stem cell-mediated repair in the spinal cord, since spinal cord injury results in drastic changes in parenchyma elasticity and viscosity. Spinal cord-derived neural precursor cells (NPCs) were grown on bis-acrylamide substrates with various rigidities. NPC growth, proliferation, and differentiation were examined and optimal in the range of normal spinal cord elasticity. In conclusion, limitations in NPC growth, proliferation, and neuronal differentiation were encountered when substrate elasticity was not within normal spinal cord tissue elasticity ranges. These studies elucidate the effect injury mediated mechanical changes may have on tissue repair by stem cells. Furthermore, this information can be applied to the development of future neuroregenerative biomaterials for spinal cord repair.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and Medical Physics</subject><subject>Biomaterials</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Biophysics</subject><subject>Cell Adhesion</subject><subject>Cell Differentiation</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Classical Mechanics</subject><subject>Elastic Modulus</subject><subject>Fibroblast Growth Factors - pharmacology</subject><subject>Intermediate Filament Proteins - physiology</subject><subject>Ki-67 Antigen - physiology</subject><subject>Microtubule-Associated Proteins - physiology</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>Nestin</subject><subject>Neurons - cytology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Spinal Cord - cytology</subject><subject>Spinal Cord - physiology</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - physiology</subject><issn>0090-6964</issn><issn>1573-9686</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkU1LHEEQhhtJ0PXjB3gJA7nkMqaqP6ePZjFqMFFQz01PT01cmd3R7unA_nt7WQ0hEMipoeupt6p4GDtGOEEA8zkhSGFrQFGD0ape77AZKiNqqxv9js0ALNTaarnH9lN6BEBshNple1xIbq3mM_bt7oGqs76nMKVq7Kvb3KYp-ql8Dj5Ni1B9H7s85FJcVT8oRz9UN5FCjmmM1ZyGofpCD_7XYoyH7H3vh0RHr-8Bu_96dje_qK-uzy_np1d1kKCmWhgLAkNHLXkpjWosYNtL3pDvOyt7A9h1jeTEkbfIDQgVELUOQpFsghAH7NM29ymOz5nS5JaLFMomfkVjTg6F4rwp55n_QKXhSpUpBf34F_o45rgqh2woLYzgxhYKt1SIY0qRevcUF0sf1w7BbZy4rRNXnLiNE7cuPR9ek3O7pO53x5uEAvAtkEpp9ZPiH6P_mfoCUmmUsw</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>Previtera, Michelle L.</creator><creator>Hui, Mason</creator><creator>Verma, Devendra</creator><creator>Shahin, Abdelhamid J.</creator><creator>Schloss, Rene</creator><creator>Langrana, Noshir A.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F28</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8D</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L6V</scope><scope>L7M</scope><scope>LK8</scope><scope>L~C</scope><scope>L~D</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>M7S</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>20130601</creationdate><title>The Effects of Substrate Elastic Modulus on Neural Precursor Cell Behavior</title><author>Previtera, Michelle L. ; Hui, Mason ; Verma, Devendra ; Shahin, Abdelhamid J. ; Schloss, Rene ; Langrana, Noshir A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-379031cdebea44758901bf428eafd94f701dd842e212b127035c1166c35e48c33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological and Medical Physics</topic><topic>Biomaterials</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Biophysics</topic><topic>Cell Adhesion</topic><topic>Cell Differentiation</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Classical Mechanics</topic><topic>Elastic Modulus</topic><topic>Fibroblast Growth Factors - pharmacology</topic><topic>Intermediate Filament Proteins - physiology</topic><topic>Ki-67 Antigen - physiology</topic><topic>Microtubule-Associated Proteins - physiology</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>Nestin</topic><topic>Neurons - cytology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Spinal Cord - cytology</topic><topic>Spinal Cord - physiology</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - drug effects</topic><topic>Stem Cells - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Previtera, Michelle L.</creatorcontrib><creatorcontrib>Hui, Mason</creatorcontrib><creatorcontrib>Verma, Devendra</creatorcontrib><creatorcontrib>Shahin, Abdelhamid J.</creatorcontrib><creatorcontrib>Schloss, Rene</creatorcontrib><creatorcontrib>Langrana, Noshir A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>SciTech Premium Collection</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>ProQuest Engineering Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ProQuest Biological Science Collection</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Annals of biomedical engineering</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Previtera, Michelle L.</au><au>Hui, Mason</au><au>Verma, Devendra</au><au>Shahin, Abdelhamid J.</au><au>Schloss, Rene</au><au>Langrana, Noshir A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Effects of Substrate Elastic Modulus on Neural Precursor Cell Behavior</atitle><jtitle>Annals of biomedical engineering</jtitle><stitle>Ann Biomed Eng</stitle><addtitle>Ann Biomed Eng</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>41</volume><issue>6</issue><spage>1193</spage><epage>1207</epage><pages>1193-1207</pages><issn>0090-6964</issn><eissn>1573-9686</eissn><abstract>The spinal cord has a limited capacity to self-repair. After injury, endogenous stem cells are activated and migrate, proliferate, and differentiate into glial cells. The absence of neuronal differentiation has been partly attributed to the interaction between the injured microenvironment and neural stem cells. In order to improve post-injury neuronal differentiation and/or maturation potential, cell–cell and cell–biochemical interactions have been investigated. However, little is known about the role of stem cell–matrix interactions on stem cell-mediated repair. Here, we specifically examined the effects of matrix elasticity on stem cell-mediated repair in the spinal cord, since spinal cord injury results in drastic changes in parenchyma elasticity and viscosity. Spinal cord-derived neural precursor cells (NPCs) were grown on bis-acrylamide substrates with various rigidities. NPC growth, proliferation, and differentiation were examined and optimal in the range of normal spinal cord elasticity. In conclusion, limitations in NPC growth, proliferation, and neuronal differentiation were encountered when substrate elasticity was not within normal spinal cord tissue elasticity ranges. These studies elucidate the effect injury mediated mechanical changes may have on tissue repair by stem cells. Furthermore, this information can be applied to the development of future neuroregenerative biomaterials for spinal cord repair.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>23429962</pmid><doi>10.1007/s10439-013-0765-y</doi><tpages>15</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0090-6964 |
| ispartof | Annals of biomedical engineering, 2013-06, Vol.41 (6), p.1193-1207 |
| issn | 0090-6964 1573-9686 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1352289967 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Biochemistry Biological and Medical Physics Biomaterials Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Biophysics Cell Adhesion Cell Differentiation Cell Proliferation Cells, Cultured Classical Mechanics Elastic Modulus Fibroblast Growth Factors - pharmacology Intermediate Filament Proteins - physiology Ki-67 Antigen - physiology Microtubule-Associated Proteins - physiology Nerve Tissue Proteins - physiology Nestin Neurons - cytology Rats Rats, Sprague-Dawley Spinal Cord - cytology Spinal Cord - physiology Stem cells Stem Cells - cytology Stem Cells - drug effects Stem Cells - physiology |
| title | The Effects of Substrate Elastic Modulus on Neural Precursor Cell Behavior |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T14%3A15%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Effects%20of%20Substrate%20Elastic%20Modulus%20on%20Neural%20Precursor%20Cell%20Behavior&rft.jtitle=Annals%20of%20biomedical%20engineering&rft.au=Previtera,%20Michelle%20L.&rft.date=2013-06-01&rft.volume=41&rft.issue=6&rft.spage=1193&rft.epage=1207&rft.pages=1193-1207&rft.issn=0090-6964&rft.eissn=1573-9686&rft_id=info:doi/10.1007/s10439-013-0765-y&rft_dat=%3Cproquest_cross%3E1347255127%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1346373279&rft_id=info:pmid/23429962&rfr_iscdi=true |