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Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

Eur J Immunol. 2014 Oct 20;

Authors: Xie L, Choudhury GR, Winters A, Yang SH, Jin K

Abstract
Forkhead box P3 (Foxp3)(+) regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the central nervous system under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ (+) CD4(+) Foxp3(+) T-cell population (cerebral Treg cells) in the normal rat cerebrum, constituting more than 15% of the cerebral CD4(+) T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the normal rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state. This article is protected by copyright. All rights reserved.

PMID: 25329858 [PubMed - as supplied by publisher]

Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice.

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Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice.

Behav Pharmacol. 2014 Oct 16;

Authors: Gatch MB, Forster MJ

Abstract
A number of cannabinoid compounds are being sold in the form of incense as 'legal' alternatives to marijuana. The purpose of these experiments was to determine whether the most common of these compounds have discriminative stimulus effects similar to Δ-tetrahydrocannabinol (Δ-THC), the main active component in marijuana. Locomotor depressant effects of JWH-018, JWH-073, JWH-200, JWH-203, JWH-250, AM-2201, and CP 47,497-C8-homolog were tested in mice. The compounds were then tested for substitution in rats trained to discriminate Δ-THC (3 mg/kg, intraperitoneally). The time course of the peak dose of each compound was also tested. Each of the synthetic cannabinoids dose-dependently decreased locomotor activity for 1-2 h. Each of the compounds fully substituted for the discriminative stimulus effects of Δ-THC, mostly at doses that produced only marginal amounts of rate suppression. JWH-250 and CP 47,497-C8-homolog suppressed response rates at doses that fully substituted for Δ-THC. The time courses varied markedly between compounds. Most of the compounds had a shorter onset than Δ-THC, and the effects of three of the compounds lasted substantially longer (JWH-073, JWH-250, and CP 47,497-C8-homolog). Several of the most commonly used synthetic cannabinoids produce behavioral effects comparable with those of Δ-THC, which suggests that these compounds may share the psychoactive effects of marijuana responsible for abuse liability. The extremely long time course of the discriminative stimulus effects and adverse effects of CP 47,497-C8-homolog suggest that CP 47,497-C8-homolog may be associated with increased hazards among humans.

PMID: 25325289 [PubMed - as supplied by publisher]

Resident Assistant Training Program for Increasing Alcohol, Other Drug, and Mental Health First-Aid Efforts.

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Resident Assistant Training Program for Increasing Alcohol, Other Drug, and Mental Health First-Aid Efforts.

Prev Sci. 2014 Oct 17;

Authors: Thombs DL, Gonzalez JM, Osborn CJ, Rossheim ME, Suzuki S

Abstract
In college and university residence halls, resident assistants (RAs) are expected to serve as first-aid providers to students who may have alcohol, other drug, mental health, and academic problems. Despite this responsibility, evidence-based, first-aid programs have not been developed and tested for the RA workforce. The current study examined effects of an investigational first-aid program designed specifically for RAs. The online Peer Hero Training program is a novel approach to RA training in its use of interactive video dramatizations of incidents involving substance-using or distressed residents. A 9-month randomized trial conducted on eight US campuses compared RAs who participated in the Peer Hero Training program to RAs who received training-as-usual. Participation in the Peer Hero Training program significantly increased RA first-aid efforts for residential students who may have had alcohol, other drug, mental health, or academic problems 6 months after baseline. Compared with those in the training-as-usual condition, RAs in the Peer Hero Training program made more than 10 times as many first-aid efforts for possible alcohol problems, almost 14 times the number of first-aid efforts for possible drug use, almost 3 times the number of first-aid efforts for possible mental health problems, and 3 times the number of first-aid efforts for academic problems. There was no evidence that measured RA attitudes mediated the effects of the intervention. Results of this preliminary evaluation trial suggest that online training using interactive video dramatizations is a viable approach to strengthening RAs' ability to provide alcohol, other drugs, and mental health first-aid to undergraduates.

PMID: 25322950 [PubMed - as supplied by publisher]

Blood pressure regulation XI: overview and future research directions.

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Blood pressure regulation XI: overview and future research directions.

Eur J Appl Physiol. 2014 Mar;114(3):579-86

Authors: Raven PB, Chapleau MW

Abstract
While the importance of regulating arterial blood pressure within a 'normal' range is widely appreciated, the definition of 'normal' and the means by which humans and other species regulate blood pressure under various conditions remain hotly debated. The effects of diverse physiological, pathological and environmental challenges on blood pressure and the mechanisms that attempt to maintain it at an optimal level are reviewed and critically analyzed in a series of articles published in this themed issue of the European Journal of Applied Physiology. We summarize here the major points made in these reviews, with emphasis on unifying concepts of regulatory mechanisms and future directions for research.

PMID: 24463603 [PubMed - indexed for MEDLINE]

Inhibition of triple-negative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies.

Recent Research Articles from UNTHSC - Sat, 10/18/2014 - 4:08am
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Inhibition of triple-negative and Herceptin-resistant breast cancer cell proliferation and migration by Annexin A2 antibodies.

Br J Cancer. 2014 Oct 16;

Authors: Chaudhary P, Thamake SI, Shetty P, Vishwanatha JK

Abstract
Background:Annexin A2 (AnxA2), a calcium-dependent phospholipid binding protein, is abundantly present at the surface of triple-negative and Herceptin-resistant breast cancer cells. Interactions between cell-surface AnxA2 and tyrosine kinase receptors have an important role in the tumour microenvironment and act together to enhance tumour growth. The mechanism supporting this role is still unknown.Methods:The membrane function of AnxA2 was blocked by incubating cells with anti-AnxA2 antibodies. Western blotting, immunoprecipitation, immunofluorescence, 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), flow cytometry, Clonogenic, and wound-healing assays were performed in this study.Results:We demonstrate that AnxA2 interacts with epidermal growth factor receptor (EGFR) at the cell surface and has an important role in cancer cell proliferation and migration by modulating EGFR functions. Blocking AnxA2 function at the cell surface by anti-AnxA2 antibody suppressed the EGF-induced EGFR tyrosine phosphorylation and internalisation by blocking its homodimerisation. Furthermore, addition of AnxA2 antibody significantly inhibited the EGFR-dependent PI3K-AKT and Raf-MEK-ERK downstream pathways under both EGF-induced and basal growth conditions, resulting in lower cell proliferation and migration.Conclusions:These findings suggest that cell-surface AnxA2 has an important regulatory role in EGFR-mediated oncogenic processes by keeping EGFR signalling events in an activated state. Therefore, AnxA2 could potentially be used as a therapeutic target in triple-negative and Herceptin-resistant breast cancers.British Journal of Cancer advance online publication 16 October 2014; doi:10.1038/bjc.2014.542 www.bjcancer.com.

PMID: 25321192 [PubMed - as supplied by publisher]

HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China.

Recent Research Articles from UNTHSC - Sat, 10/18/2014 - 4:08am
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HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China.

BMJ Open. 2014;4(10):e005886

Authors: Leng X, Liang S, Ma Y, Dong Y, Kan W, Goan D, Hsi JH, Liao L, Wang J, He C, Zhang H, Xing H, Ruan Y, Shao Y

Abstract
OBJECTIVE: To explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China.
DESIGN: A series of cross-sectional surveys from 2003 to 2012 from the Chinese National HIV Drug Resistance (HIVDR) Surveillance and Monitoring Network.
SETTING: China.
PARTICIPANTS: Data were analysed by the Chinese National (HIVDR) Surveillance and Monitoring Network from 2003 to 2012. Demographic, ART and laboratory data (CD4+ cell count, viral load and drug resistance) were included. Factors associated with virological failure were identified by logistic regression analysis.
RESULTS: 929 of the 8556 individuals in the Chinese HIVDR database were IDUs receiving first-line ART. For these 929 IDUs, the median duration of treatment was 14 months (IQR 6.0-17.8). 193 of the 929 IDUs (20.8%) experienced virological failure (HIV viral load ≥1000 copies/mL). The prevalence of HIVDR among patients with virological failure was 38.9% (68/175). The proportion of patients with drug resistance to non-nucleoside reverse transcriptase inhibitor (NNRTIs), nucleoside reverse transcriptase inhibitor (NRTIs) and protease inhibitors (PIs) was 52.9%, 76.5% and 4.4%, respectively. Factors independently associated with virological failure include: ethnic minorities, junior high school education or less, farmers, self-reported missing doses in the past month, CD4 cell count at survey from 200 to 349 cells/mm(3) or from 0 to 199 cells/mm(3), and residence of Guangxi and Yunnan provinces.
CONCLUSIONS: The proportion of virological failure was high among IDUs receiving first-line ART in China. However, better treatment outcomes were observed in Guangxi and Yunnan, which indicates the importance of ART education and adherence to intervention, especially for patients who are farmers, minorities or have a poor educational background.

PMID: 25319999 [PubMed - in process]

Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.

Recent Research Articles from UNTHSC - Fri, 10/17/2014 - 12:05pm
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Involvement of p38 MAPK in reactive astrogliosis induced by ischemic stroke.

Brain Res. 2014 Mar 10;1551:45-58

Authors: Roy Choudhury G, Ryou MG, Poteet E, Wen Y, He R, Sun F, Yuan F, Jin K, Yang SH

Abstract
Reactive astrogliosis is an essential feature of astrocytic response to all forms of central nervous system (CNS) injury and disease, which may benefit or harm surrounding neural and non-neural cells. Despite extensive study, its molecular triggers remain largely unknown in term of ischemic stroke. In the current study we investigated the role p38 mitogen-activated protein kinase (MAPK) in astrogliosis both in vitro and in vivo. In a mouse model of middle cerebral artery occlusion (MCAO), p38 MAPK activation was observed in the glia scar area, along with increased glial fibrillary acidic protein (GFAP) expression. In primary astrocyte cultures, hypoxia and scratch injury-induced astrogliosis was attenuated by both p38 inhibition and knockout of p38 MAPK. In addition, both knockout and inhibition of p38 MAPK also reduced astrocyte migration, but did not affect astrocyte proliferation. In a mouse model of permanent MCAO, no significant difference in motor function recovery and lesion volume was observed between conditional GFAP/p38 MAPK knockout mice and littermates. While a significant reduction of astrogliosis was observed in the GFAP/p38 knockout mice compared with the littermates. Our findings suggest that p38 MAPK signaling pathway plays an important role in the ischemic stroke-induced astrogliosis and thus may serve as a novel target to control glial scar formation.

PMID: 24440774 [PubMed - indexed for MEDLINE]

Ancient human genomes suggest three ancestral populations for present-day Europeans.

Recent Research Articles from UNTHSC - Thu, 10/16/2014 - 4:04am
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Ancient human genomes suggest three ancestral populations for present-day Europeans.

Nature. 2014 Sep 18;513(7518):409-13

Authors: Lazaridis I, Patterson N, Mittnik A, Renaud G, Mallick S, Kirsanow K, Sudmant PH, Schraiber JG, Castellano S, Lipson M, Berger B, Economou C, Bollongino R, Fu Q, Bos KI, Nordenfelt S, Li H, de Filippo C, Prüfer K, Sawyer S, Posth C, Haak W, Hallgren F, Fornander E, Rohland N, Delsate D, Francken M, Guinet JM, Wahl J, Ayodo G, Babiker HA, Bailliet G, Balanovska E, Balanovsky O, Barrantes R, Bedoya G, Ben-Ami H, Bene J, Berrada F, Bravi CM, Brisighelli F, Busby GB, Cali F, Churnosov M, Cole DE, Corach D, Damba L, van Driem G, Dryomov S, Dugoujon JM, Fedorova SA, Gallego Romero I, Gubina M, Hammer M, Henn BM, Hervig T, Hodoglugil U, Jha AR, Karachanak-Yankova S, Khusainova R, Khusnutdinova E, Kittles R, Kivisild T, Klitz W, Kučinskas V, Kushniarevich A, Laredj L, Litvinov S, Loukidis T, Mahley RW, Melegh B, Metspalu E, Molina J, Mountain J, Näkkäläjärvi K, Nesheva D, Nyambo T, Osipova L, Parik J, Platonov F, Posukh O, Romano V, Rothhammer F, Rudan I, Ruizbakiev R, Sahakyan H, Sajantila A, Salas A, Starikovskaya EB, Tarekegn A, Toncheva D, Turdikulova S, Uktveryte I, Utevska O, Vasquez R, Villena M, Voevoda M, Winkler CA, Yepiskoposyan L, Zalloua P, Zemunik T, Cooper A, Capelli C, Thomas MG, Ruiz-Linares A, Tishkoff SA, Singh L, Thangaraj K, Villems R, Comas D, Sukernik R, Metspalu M, Meyer M, Eichler EE, Burger J, Slatkin M, Pääbo S, Kelso J, Reich D, Krause J

Abstract
We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

PMID: 25230663 [PubMed - indexed for MEDLINE]

A useful mouse model of glucocorticoid-induced ocular hypertension.

Recent Research Articles from UNTHSC - Thu, 10/16/2014 - 4:04am
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A useful mouse model of glucocorticoid-induced ocular hypertension.

Invest Ophthalmol Vis Sci. 2014 Aug;55(8):4934

Authors: Clark AF

PMID: 25108005 [PubMed - indexed for MEDLINE]

Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

Recent Research Articles from UNTHSC - Wed, 10/15/2014 - 4:05am
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Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

PLoS One. 2013;8(12):e84425

Authors: Funari VA, Winkler M, Brown J, Dimitrijevich SD, Ljubimov AV, Saghizadeh M

Abstract
MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC) in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6) and diabetic (n=6) central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR) and by in situ hybridization (ISH) in independent samples. HCEC were transfected with human pre-miR™miRNA precursors (h-miR) or their inhibitors (antagomirs) using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

PMID: 24376808 [PubMed - indexed for MEDLINE]

Sigma-1 Receptor Stimulation Protects Retinal Ganglion Cells from Ischemia-Like Insult through the Activation of Extracellular-Signal-Regulated Kinases1/2.

Recent Research Articles from UNTHSC - Tue, 10/14/2014 - 4:05am
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Sigma-1 Receptor Stimulation Protects Retinal Ganglion Cells from Ischemia-Like Insult through the Activation of Extracellular-Signal-Regulated Kinases1/2.

Exp Eye Res. 2014 Oct 8;

Authors: Mueller BH, Park Y, Ma HY, Dibas A, Ellis DZ, Clark AF, Yorio T

Abstract
Sigma-1 receptor (σ-1) activation and mitogen-activated protein kinases (MAPKs) have been shown to protect retinal ganglion cells (RGCs) from cell death. The purpose of this study was to determine if σ-1 receptor stimulation with pentazocine could promote neuroprotection under conditions of an ischemia-like insult (oxygen glucose deprivation (OGD)) through the phosphorylation of extracellular signal regulated kinase (pERK)1/2. Primary RGCs were isolated from P3-P7 Sprague-Dawley rats and purified by sequential immunopanning using Thy 1.1 antibodies. RGCs were cultured for 7 days before subjecting the cells to an OGD insult (0.5% oxygen in glucose-free medium) for 6 hours. During the OGD, RGCs were treated with pentazocine (σ-1 receptor agonist) with or without BD 1047 (σ-1 receptor antagonist). In other experiments, primary RGCs were treated with pentazocine in the presence or absence of an MEK1/2 inhibitor, PD098059. Cell survival/death was assessed by staining with the calcein-AM/ethidium homodimer reagent. Levels of pERK1/2, total ERK1/2, and beta tubulin expression were determined by immunoblotting and immunofluorescence staining. RGCs subjected to OGD for 6 hours induced 50% cell death in primary RGCs (p<0.001) and inhibited pERK1/2 expression by 65% (p<0.001). Cell death was attenuated when RGCs were treated with pentazocine under OGD (p<0.001) and pERK1/2 expression was increased by 1.6 fold (p<0.05) compared to OGD treated RGCs without pentazocine treatment. The co-treatment of PD098059 (MEK 1/2 inhibitor) with pentazocine significantly abolished the protective effects of pentazocine on the RGCs during this OGD insult. Activation of the σ-1 receptor is a neuroprotective target that can protect RGCs from an ischemia-like insult. These results also established a direct relationship between σ-1 receptor stimulation and the neuroprotective effects of the ERK1/2 pathway in purified RGCs subjected to OGD. These findings suggest that activation of the σ-1 receptor may be a therapeutic target for neuroprotection particularly relevant to ocular neurodegenerative diseases that effect RGCs..

PMID: 25305575 [PubMed - as supplied by publisher]

In vivo assessment of smt 19969 in a hamster model of clostridium difficile infection

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Weiss, W. | Pulse, M. | Vickers, R.
Publication year: 2014
Journal / Book title: Antimicrobial Agents and Chemotherapy

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Pregnancy Research on Osteopathic Manipulation Optimizing Treatment Effects: the PROMOTE study

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Hensel, K.L. | Buchanan, S. | Brown, S.K. | Rodriguez, M. | Cruser, d.A.
Publication year: 2014
Journal / Book title: American Journal of Obstetrics and Gynecology

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Using modified approaches on marginal regression analysis of longitudinal data with time-dependent covariates

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Zhou, Y. | Lefante, J. | Rice, J. | Chen, S.
Publication year: 2014
Journal / Book title: Statistics in Medicine

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Unsilencing voices: a study of zoo signs and their language of authority

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Fogelberg, K.
Publication year: 2014
Journal / Book title: Cultural Studies of Science Education

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Molecular genetic investigative leads to differentiate monozygotic twins

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Budowle, B.
Publication year: 2014
Journal / Book title: Investigative Genetics

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PTEN degradation after ischemic stroke: A double-edged sword

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Li, W. | Huang, R. | Chen, Z. | Yan, L.-J. | Simpkins, J.W. | Yang, S.-H.
Publication year: 2014
Journal / Book title: Neuroscience

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Characterization of [3H]LS-3-134, a novel arylamide phenylpiperazine D3 dopamine receptor selective radioligand

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Rangel-Barajas, C. | Malik, M. | Taylor, M. | Neve, K.A. | Mach, R.H. | Luedtke, R.R.
Publication year: 2014
Journal / Book title: Journal of Neurochemistry

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What Role Does Sleep Play in Weight Gain in the First Semester of University?

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Roane, B.M. | Seifer, R. | Sharkey, K.M. | Van Reen, E. | Bond, T.L.Y. | Raffray, T. | Carskadon, M.A.
Publication year: 2014
Journal / Book title: Behavioral Sleep Medicine

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Platinum(IV) cisplatin derivative trans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV) has an enhanced therapeutic index compared to cisplatin for the treatment of non-small cell lung cancer

Latest UNTHSC Articles in Scopus - Sun, 10/12/2014 - 4:04pm
Author(s):Shi, Y. | Koneru, B. | Redfearn, W. | Miller, M.L. | Myers, L. | Di Pasqua, A.J.
Publication year: 2014
Journal / Book title: Inorganica Chimica Acta

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