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Dissertations / Theses on the topic 'Alpha9'

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Published: 9 March 2023
Last updated: 10 March 2023

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1

Baumann, Lisa [Verfasser]. "Der Einfluss der alpha9- und alpha10-Untereinheit des nikotinischen Acetylcholinrezeptors auf den Knochenstoffwechsel / Lisa Baumann." Gießen : Universitätsbibliothek, 2019. http://d-nb.info/1193920868/34.

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2

Madrid, López Natalia Gabriela. "Ciclo sueño-vigilia de una cepa de ratón Knock-Out para el receptor colinérgico nicotínico alpha9." Tesis, Universidad de Chile, 2017. http://repositorio.uchile.cl/handle/2250/147545.

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Grado de magíster en neurociencias
Los estados de sueño y vigilia son configuraciones estables del Sistema Nervioso que pueden ser influenciados por modificaciones de los sistemas sensoriales. El estudio del ciclo de sueño-vigilia de un ratón genéticamente modificado que carece de un receptor en la cóclea dio resultados que muestran diferencias en la organización de los estados de vigilia y sueño, a demás de distinta duración de los episodios de sueño y enmascaramiento fótico que afecta de manera distinta a los ratones control y genéticamente modificados.
The states of sleep and wakefulness are stable configurations of the nervous system that can be influenced by modifications of the sensory systems. The study of the sleep-wakefulness cycle of a genetically modified mouse that lacks a receptor in the cochlea gave results that show differences in the organization of the sleep and wakefulness states, in addition to different duration of the sleep episodes and the photic masking that affect control mice and genetically modified mice differently.
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3

BAVO, FRANCESCO. "SUBTYPE-SELECTIVE NEURONAL NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS AND ANTAGONISTS." Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/607332.

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This PhD thesis focuses on two specific targets, belonging to the same receptor class of Nicotinic Acetylcholine Receptors (nAChRs): the α4β2 subtype and the α7 subtype. This elaborate is divided in two parts. The aim of the first part is the design and synthesis of α4β2 selective partial agonists as potential smoking-cessation agents. The aim of the second part is the design and synthesis of α7 antagonists with mitocan properties as antitumoral agents. Part 1. In the first project, a series of 3-nitrophenyl ethers and 3-hydroxyphenyl ethers of (S)-N-methylprolinol bearing bulky and lipophilic substituents at the C5 were designed, synthesized and assayed as putative selective α4β2 ligands. Two of them, 5-substituted with a 6-hydroxy-1-hexynyl, had high α4β2 affinity and increased α4β2/α3β4 selectivity when compared with the correspondent unsubstituted parent compounds. In the second project, each -CH= of the unselective antagonist (S,R)-N-methyl-2-pyrrolidinyl-1,4-benzodioxane and of its epimer at the benzodioxane stereocenter, was replaced by a nitrogen. The resulting four diastereomeric pairs of pyrrolidinyl-pyridodioxanes, also designed as the product of rigidification of the flexible scaffolds of pyridyl ethers of N-methyl prolinol, were studied for their nicotinic affinity at the α4β2 and α3β4. The isosteric -CH= to N substitution was detrimental for all the compounds, with the only exception of N-Methyl-pyrrolidinyl 5-pyridodioxane, with the nitrogen at position 5. Indeed, this ligand had similar affinity to its benzodioxane parent compound, but it had high α4β2/α3β4 selectivity and it was shown to be a selective partial agonist. In the third project, the unselective antagonist (S,R)-N-methyl-2-pyrrolidinyl-1,4-benzodioxane and of its epimer at the benzodioxane stereocenter were substituted at position 5 of the benzodioxane moiety, to explore the possibility of introducing selectivity and/or partial agonist as previously done with -CH= to N replacement. Among the synthesized compounds, (S,S)-N-Methyl-pyrrolidinyl-5-amino-benzodioxane had slightly improved affinity at the α4β2 affinity and highly enhanced α4β2/α3β4 selectivity than the unsubstituted parent compound, and it was shown to be a very potent partial agonist. In the fourth project, we applied computational techniques to support the interpretation of the biological results regarding N-Methyl-pyrrolidinyl 5-substituted benzodioxanes and pyridodioxanes. From these findings, we suggested that partial agonism and α4β2/α3β4 selectivity could be achieved when the benzodioxane scaffold is appropriately substituted with an HBA/HBD system, that can displace a water molecule from a small and hydrophilic subpocket of the binding site. Part 2. Adenocarcinoma and glioblastoma cell lines express α7 and α9-α10 nAChRs, whose activation promotes tumor cells growth. On these cells, the triethylammoniumethyl ether of 4-stilbenol MG624, a known selective antagonist of α7 and α9-α10 nAChRs, has antiproliferative activity. The structural analogy of MG624 with the mitocan RDM- 4’BTPI, triphenylphosphoniumbutyl ether of pterostilbene, suggested us that molecular hybridization among their three substructures might result in novel antitumour agents with higher potency and selectivity. We found that replacement of ethylene with butylene in the triethylammonium derivatives results in more potent and selective toxicity towards adenocarcinoma and glioblastoma cells, which was paralleled by increased α7 and α9-α10 nAChR antagonism and improved ability of reducing mitochondrial ATP production. Further elongation to octylene (26) provided a compound with 40-fold and 10-fold increased antiglioblastoma and antiadenocarcinoma activity respectively, when compared to MG624. Elongation of the alkylene linker was greatly advantageous also for the triphenylphosphonium derivatives. RDM- 4’BTPI did not acquire, as expectable, antinicotinic activity by hybridization with MG624 stilbene scaffold, but it was surpassed in glioblastoma cell viability reduction by its stilbene analogues with > 4C alkylene linker. In particular, the analogue with decylene between stilbenoxyl and triphenylphosphonium head (24) was ten- fold and two-fold more potent than RDM-4’BTPI in reducing glioblastoma cell viability and in increasing ROS production respectively. Overall, the ammonium compound 26 reached antiproliferative activities at glioblastoma and adenocarcinoma cells in the same range of the phosphonium 24, but showed good selectivity against neuroblastoma and healthy mouse astrocytes.
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4

Spies, Markus. "Nikotinische Rezeptoren nozizeptiver Neurone : Lokalisation und Charakterisierung der {[alpha]3- [Alpha3-] und {[alpha]5-Untereinheiten [Alpha5-Untereinheiten] /." Giessen : VVB Laufersweiler, 2007. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=016297581&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

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5

Ochoa, Vanessa. "Nicotinic Signaling: Alpha3 Beta4 Heteromers, Alpha5 Subunits, And The Prototoxin Lypd6b." ScholarWorks @ UVM, 2015. http://scholarworks.uvm.edu/graddis/472.

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Prototoxin proteins have been identified as members of the Ly6/uPAR super family whose three-finger motif resembles that of α-bungarotoxin. Though they are known to modify the function of nAChRs, their specificity is still unclear. Our lab identified three prototoxin proteins in the chicken ciliary ganglion: Ch3ly, Ch5ly, and Ch6ly. Ch6ly was later identified as prostate stem cell antigen (PSCA), and specifically decreased the amount of calcium influx through the homomeric α7 nAChR subtype. I then identifiedCh3ly and Ch5ly as LY6E and LYPD6B, respectively. I focused my attention onLYPD6B because of its expression in the brain. This dissertation tests whether LYPD6Bis a prototoxin protein that specifically co-localizes with and modifies the function of the heteromeric α3β4* nAChRs (the other nAChR subtype expressed in the chicken ciliary ganglia). In the first part of my dissertation I performed intracellular two-electrode voltage clamp on Xenopus oocytes co-expressing human LYPD6B and different stoichiometries of the α3β4* nAChR, these included two (α3)2(β4)3 withβ4−α3−β4−β4−α3 and β4−α3−β4−α3−β4 stoichiometries, two (α3)3(β4)2 with stoichiometries β4−α3−α3−β4−α3 and β4−α3−β4−α3−α3, two (α3β4)2(α5D)β4−α3−α5D−β4−α3 and β4−α3−β4−α3−α5D, and (α3β4)2(α5N) with stoichiometries β4−α3−α5N−β4−α3 and β4−α3−β4−α3−α5N. Concatemeric constructs are designed to link nAChR subunits, thus when translated it is done so as a single polypeptide. LYPD6Bincreased the acetylcholine (ACh) potency and desensitization rate, but decreased the maximum current response (Imax) for the (α3)3(β4)2 nAChR subtype. Yet, LYPD6Bonly decreased the Imax for the (α3β4)2α5 D-variant and not the N-variant (associated with increase nicotine consumption). For the second part of my dissertation, I determined if the expression of LYPD6B correlated with nAChRs in an activity dependent manner. Though LYPD6B mRNA expression correlates with nAChR subunit mRNA expression levels, it seemed to be independent of nAChR activity. To determine if fluorescent colocalization occurs between LYPD6B and a specific nAChR subtype, I genetically engineered LYPD6B to express a human influenza hemagglutinin (HA) epitope tag and cloned into a chicken retrovirus. LYPD6B was shown to co-localize only with the α3β4*heteromeric and not the homomeric α7 nAChRs, in a nAChR activity dependent manner. This study adds to the complexity of a prototoxin’s function by suggesting that the specificity is dependent on nAChR type and stoichiometry. It is the first in identifying a prototoxin protein, LYPD6B, which specifically modulates the function of the(α3)3(β4)2 and (α3β4)2(α5 D-variant) heteromeric nAChR subtypes. For the (α3β4)2(α5D-variant) nAChR subtype LYPD6B decreased the Imax. Such observation may be telling of a novel mechanism involved with nicotine dependence. For the(α3)3(β4)2 nAChR subtype LYPD6B increases its ACh sensitivity, desensitization rate, while decreasing Imax. Additionally, the co-localization of LYPD6B and α3β4* nAChRsin the lack of nAChR activity highlights the relevance of the functional effects α3β4*nAChRs exhibit due to LYPD6B. Such relevance may be the utilization of limiting Ach amounts.
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6

Xu, Xiaohong. "Shared long-range regulatory elements coordinate expression on the nAChR beta4/alpha3/alpha5 cluster." Connect to text online, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1157660172.

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7

Xu, Xiaohong. "SHARED LONG-RANGE REGULATORY ELEMENTS COORDINATE EXPRESSION OF THE NACHR BETA4/ALPHA3/ALPHA5 CLUSTER." Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1157660172.

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8

Schäfer, Heike. "Untersuchung der Proteinalterung am Beispiel des [alpha]A-Crystallins [alphaA-Crystallins] der Augenlinse mittels proteomanalytischer Methoden." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972090770.

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9

Ponchel, Guillaume. "Etudes structurales et fonctionnelles de deux alpha-galactosidases actives sur les antigènes B et alpha3 Gal." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4017.

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Les conversions enzymatiques des antigènes du système des groupes sanguins ABO et de l'antigène majeur de xénotransplantation α3Gal représentent des alternatives thérapeutiques afin d'améliorer l'approvisionnement des hôpitaux en sang de groupe O et la transplantation d'organes. La famille GH110 des glycoside hydrolases comprend des enzymes actives sur les antigène B et α3Gal à pH neutre et fonctionnant avec un mécanisme catalytique par inversion. La sous‐famille GH110_A regroupe des membres actifs exclusivement sur l'antigène B, tandis que la sous‐famille GH110_B regroupe des membres actifs sur les antigènes B et α3Gal. Le travail présenté dans ce manuscrit décrit les études structurales et fonctionnelles de deux α‐galactosidases, BtGal110A (GH110_A) et BtGal110B (GH110_B), de la famille GH110 provenant de la bactérie commensale Bacteroides thetaiotaomicron et représentatives des chacune des ces deux sous‐familes. La spécificité de substrat et la grande efficacité catalytique de ces enzymes à pH neutre ont été confirmées grâce à des oligosaccharides mimant l'extrémité des antigènes B et α3Gal. BtGal110A et BtGal110B se replient en hélice β droite et se distinguent d'autres protéines au repliement similaire par la présence de deux domaines additionnels qui adoptent un repliement en demi tonneau β et participent à l'architecture du site actif. La machinerie catalytique de BtGal110A et BtGal110B est constituée de trois acides aspartiques, semblable à celle des enzymes des familles GH28 et GH49, qui partagent la même repliement en hélice &#946
Enzymatic conversions of the ABO blood group antigens and of the major xenotransplantation α3Gal antigen represent therapeutic alternatives intended to improve supply of hospitals with requested blood type O and organs. The family GH110 of glycoside hydrolases includes enzymes active towards B and α3Gal antigen within neutral pH and employs an inverting catalytic mechanism. The GH110_A subfamily gathers enzymes with exquisite substrate specificity towards the B antigen, while the GH110_B subfamily gathers enzymes active towards the B and the α3Gal antigens. The present manuscript describes the functional and structural studies of two α‐galactosidases BtGal110A (GH110_A) and BtGal110B (GH110_B) from the commensal bacteria Bacteroides thetaiotaomicron, two representative members of each of these two subfamilies. The substrate specificity and high catalytic efficiency of these enzymes at neutral pH were confirmed using oligosaccharides corresponding to the terminal carbohydrate sequences of the B and α3Gal antigens. BtGal110A and BtGal110B contain a right‐handed β‐helix, but he presence of two additional domains tfolded as half β‐barrels, which participate to the architecture of the active site distinguishes BtGal110A and BtGal110B fro other related glycoside hydrolases. The catalytic machinery consists of three aspartic acids, reminiscent of that of enzymes from the GH28 and GH49 families, which share a similar β‐helix fold. Our observations support the membership of family GH110 to the clan‐N of glycoside hydrolases
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10

Solda', G. M. E. A. "Alpha3 and alpha5 neuronal nicotinic receptor subunit genes : a case of tail-to-tail overlap in humans." Doctoral thesis, Università degli Studi di Milano, 2005. http://hdl.handle.net/2434/47108.

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Natural antisense transcripts, because of their potential to form double-stranded RNA (dsRNA) molecules, recently emerged as a mechanism acting on eukaryotic gene regulation at multiple levels. CHRNA3 and CHRNA5, coding for alpha3 and alpha5 subunits of the neuronal nicotinic acetylcholine receptor, have been reported to overlap at their 3'ends in human and bovine genomes. The general goal of this PhD project was the structural and functional study of this overlap. A fine characterization of human CHRNA3 and CHRNA5 alternative transcripts allowed a more precise definition of the overlap extent and highlighted a complex web of possible sense-antisense interactions among overlapping mRNAs. An RNase protection-based approach was used to detect in vivo RNA-RNA duplexes of CHRNA3 and CHRNA5 transcripts, which resulted to be present in human but not in bovine cells. Furthermore, levels of overlapping transcripts were determined by real-time RT-PCR both in humans and in cattle. Finally, some possible functional consequences of this overlap were explored.
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11

Gräf, Thorsten. "Hemmung der Angiogenese in vitro durch Antisense-Oligonukleotide gegen die [alpha]v-Kette [alphav-Kette] des Vitronectin-Rezeptors." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=970795068.

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12

Jung, Simon. "Genexpressionsuntersuchungen von alpha 1c, alpha2/delta, beta, SERCA 2a und Phospholamban in Endomyokardbiopsien von Patienten mithypertrophisch obstruktiver Kardiomyopathie." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-43846.

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13

Pan, Ruping [Verfasser]. "Analyses of differential effects of alpha1 AMPK and alpha2 AMPK on survival and metabolism in cardiac cells / Ruping Pan." Gießen : Universitätsbibliothek, 2014. http://d-nb.info/1068825510/34.

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14

Baumann, Thomas. "Organokatalytische Synthesestrategien zur Darstellung [alpha],[alpha]-disubstituierter [alpha, alpha-disubstuierter] Aminosäurederivate." Berlin Logos-Verl, 2007. http://deposit.d-nb.de/cgi-bin/dokserv?id=3025324&prov=M&dok_var=1&dok_ext=htm.

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15

Vogt, Henning. "Organo catalytic strategies towards [alpha], [alpha] [alpha, alpha] disubstituted amino acid derivatives." Berlin Logos-Verl, 2006. http://deposit.d-nb.de/cgi-bin/dokserv?id=2861590&prov=M&dok_var=1&dok_ext=htm.

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16

Mutz, Diana. "Identifizierung von Bindungspartnern des cytosolischen Teils der [alpha]3-Integrin-Untereinheit [Alpha3-Integrin-Untereinheit] und die Aufklärung ihrer Rolle bei der Funktion des [alpha]3[beta]1-Integrins [Alpha3beta1-Integrins]." [S.l. : s.n.], 2004. http://www.diss.fu-berlin.de/2004/214/index.html.

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17

Kim, Hee-Cheol. "[Alpha], [Alpha], [alpha]'-Dicarbonyl-Oxime [Alpha-Dicarbonyl-Oxime] Eigenschaften und Anwendungen in der elektrochemischen Delignifizierung /." [S.l. : s.n.], 2001. http://archiv.ub.uni-marburg.de/diss/z2001/0365/.

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18

Peterson, Daniel J., Courtney M. Bardo, Elizabeth D. Cummins, and Russell W. Brown. "The Role of the Alpha7 and Alpha4 Beta2 Nicotinic Receptors in Nicotine Sensitization and Neural Plasticity in Rats Neonatally Treated with Quinpirole." Digital Commons @ East Tennessee State University, 2015. https://dc.etsu.edu/etsu-works/959.

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Aims: We have established that neonatal treatment with quinpirole, a dopamine D2/D3 agonist, results in increases of dopamine D2 receptor sensitivity throughout the animal’s lifetime and has a number of consistencies with schizophrenia. Aim 1: Analyze the roles of α7 and α4β2 nicotinic receptors in nicotine sensitization in adolescent male and female rats neonatally treated with quinpirole. Aim 2: The roles of the α7 and α4β2 nicotinic receptors were analyzed in their effects on Brain-Derived Neurotrophic Factor (BDNF) and mammalian target of rapamycin (mTOR) in rats neonatally treated with quinpirole and sensitized to nicotine. Methods: Animals were neonatally treated with quinpirole or saline from postnatal days (P)1-21. Beginning on P33, animals were ip injected with nicotine (0.5 mg/kg free base) or saline and tested every second day from P33-49. Approximately 15-30 min before the nicotine or saline injection, animals were ip injected with either the α7 nicotinic receptor (nAChR) antagonist methllycacontine (MLA; 2 or 4 mgkg) or the α4β2 nAChR antagonist dihyro-β (DhβE; 1 or 2.5 mg/kg) erythrodine. Brain tissue was taken 24 h after the last day of testing. Results: Neonatal quinpirole enhanced nicotine sensitization and DhβE blocked nicotine sensitization regardless of neonatal treatment and was more effective in blocking sensitization in males versus females. MLA failed to block nicotine sensitization. Howeer, MLA blocked the acute hypoactive response to nicotine in males, and the higher dose of MLA reduced sensitization in males. Neonatal quinpirole sensitized the accumbal BDNF response to nicotine, but neonatal quinpirole resulted in a decrease of mTOR in both brain areas. Conclusions: The α4β2 receptor plays a critical role in adolescent nicotine sensitization. Interstingly, the α7 nAChR appears to be important in the acute response to nicotine and is more important in nicotine sensitization in males. Both nAChRs appear to be important in accumbal BDNF and their roles will be analyzed in the mTOR response.
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19

Elend, Almut S. "#alpha#,#alpha#-disubstituted glycines : asymmetric synthesis." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244599.

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20

Gangadharan, Denise Michelle. "Thymic development of CS8[alpha][alpha]⁺ TCR[alpha][beta]⁺ agonist selected IEL." Diss., Connected to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3189998.

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Thesis (Ph. D.)--University of California, San Diego, 2005.
Title from first page of PDF file (viewed Marc 6, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 100-116).
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21

ALTENBURGER, JEAN-MICHEL. "Inhibiteurs de type alpha, alpha-difluoro alpha-aminocetone, inhibiteurs potentiels de proteases." Université Louis Pasteur (Strasbourg) (1971-2008), 1990. http://www.theses.fr/1990STR13111.

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Les syntheses totales de differents inhibiteurs de thrombine (3) ou de la protease du virus de l'imunodeficience (5) sont decrites. Ces inhibiteurs sont des analogues peptidiques du substrat naturel de ces proteases dont la liaison amide hydrolysable a ete remplacee par un groupement difluoromethylenecetone stable. Le principe de la synthese repose sur l'utilisation d'une reaction de type reformatsky entre le bromodifluoroacetate d'ethyle et un alpha-aminoaldehyde. La mise au point de conditions specifiques et particulieres a l'utilisation de substrats comportant des groupements nitres aromatique ou aliphatique a ete developpee. Ceci a donne acces a des synthons polyfonctionnalises, branches ou heterocycliques, porteurs de plusieurs fonctions amines differenciables. Une synthese avec retention de configuration d'un alpha, beta-diaminopropanaldehyde bisprotege cristallin a ete realisee au depart de l'acide r ou s aspartique. De plus, des derives de l'acide alpha-amino gamma-nitro-butyrique ont ete obtenus par une voie de synthese originale a partir de la d,l serine via une addition de michael
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22

Otto, Andreas. "Ringtransformationen an chiralen [alpha]-Alkylidenlactonen [Alpha-Alkylidenlactonen]." [S.l. : s.n.], 1999. http://deposit.ddb.de/cgi-bin/dokserv?idn=958249334.

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23

Aygün, Hüseyin Hayrullah. "Faltung des [alpha]-Amylaseinhibitors [Alpha-Amylaseinhibitors] Tendamistat." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=966236386.

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24

Langran-Goldsmith, A. E. "Alpha, alpha-dialkylglycines as amino-acid analogues." Thesis, University of Exeter, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.353998.

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25

Laplantine, Emmanuel. "Interactions au niveau des domaines intracellulaires des sous-unites alpha3a, alpha6a et beta1a des integrines." Paris 6, 2000. http://www.theses.fr/2000PA066262.

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Les adhesions focales (af) constituent un lien essentiel entre la matrice extracellulaire et le cytosquelette, ainsi que le site de transmission de signaux par les integrines. Les integrines 31 et 61, recepteurs des laminines, different dans leur specificite de reconnaissance : la laminine 1 se lie a l'integrine 61 seulement et l'adherence des cellules a ce substrat entraine la formation d'af distinctes de celles formees sur d'autres isoformes de laminine liant a la fois 31 et 61. L'integrine 31 pourrait donc reguler de maniere transdominante l'integrine 61. Afin de tester cette hypothese, des peptides representant le domaine intracellulaire des sous-unites 3a ou 6a d'integrines ont ete injectes dans des fibroblastes vivants adheres a la laminine 1. Seule la microinjection du peptide 3a entraine une reorganisation specifique des af, rappelant celles formees lors de l'activation du recepteur 31 par ses ligands. De plus, des etudes par resonance plasmonique de surface (spr) permettent de detecter une interaction directe entre les peptides correspondant aux domaines intracellulaires des sous-unites 3a et 1a d'integrine. Enfin, un criblage de banque d'adnc avec le domaine intracellulaire de la sous-unite 3a comme amorce dans le systeme double hybride chez la levure, a permis l'identification de plusieurs partenaires d'interaction. Parmi ceux-ci, la proteine dral/fhl2 interagit avec l'integrine 31 in vivo. En conclusion, differentes interactions specifiques au domaine intracellulaire de la sous-unite 3a, contribuent a la regulation de l'organisation des af par l'integrine 31. Par ailleurs, nous avons examine la contribution du domaine intracellulaire de la sous-unite 1a dans le phenomene de clustering des integrines. Des analyses en spr revelent une affinite du domaine intracellulaire de 1a pour lui-meme. Des experiences en gel filtration et en sds-page montrent que ce domaine forme des multimeres qui, d'apres des mesures en dichroisme circulaire, adoptent une structure en helice. L'oligomerisation et le changement de structure secondaire du domaine intracellulaire de la sous-unite 1a pourraient intervenir de maniere active dans l'agregation des integrines et la formation des af.
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26

Widyan, Khalid. "A novel approach to 4-functionalized imidazolidin-2-ones, [alpha]-hydroxyhydroxamic [alpha-hydroxyhydroxamic] acids and [alpha]-hydroxyamidoximes [alpha-hydroxyamidoximes]." [S.l. : s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975120360.

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27

Gulea, Mihaela. "Réarrangement [2,3]-sigmatropique de Wittig d'anions alpha-phosphoriques alpha-hétérosubstitués. Synthèse asymétrique de phosphonates alpha-hydroxylés ou alpha-aminés." Rouen, 1997. http://www.theses.fr/1997ROUES003.

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Ce travail décrit la première étude du réarrangement [2,3]-sigmatropique de Wittig qui utilise le groupe phosphonate pour stabiliser le carbanion alpha-hétérosubstitué. Cette réaction constitue une nouvelle voie d'accès à des phosphonates alpha-hétérosubstitués, avec des possibilités de contrôle stéréochimique. Le réarrangement [2,3]-sigmatropique des carbanions d'(alpha-allyloxy)-méthylphosphonates a permis d'obtenir des alpha-hydroxyphosphonates gamma, delta-insaturés diversement substitués. Les carbanions d'éthers allyliques alpha-phosphonylés alpha-carboxylés ou alpha-diphosphonylés conduisent, via les alcoolates intermédiaires réarrangés au phosphate ou au phosphate-phosphonate respectivement. Le réarrangement aza-[2,3]-sigmatropique de Wittig des carbanions dérivés du (N-allyl-N-phénylamino) méthylphosphonate de diéthyle ou des aminophosphonates allyliques dont l'atome d'azote est protégé par un groupe électroattracteur, n'a pas pu être mis en évidence. Par contre, les ylures résultant de la métallation des sels d'ammonium alpha-phosphonylés dont l'azote porte un groupe allylique se réarrangent en alpha-(N,N-diéthylamino) alcénylphosphonates correspondants. La réaction a été étendue en série propargylique et benzylique, ainsi qu'en série des ylures des alpha-aminophosphonates alpha-phosphonylés ou alpha-carboxylés, conduisant à de nouveaux phosphonates polyfonctionnalisés. Utilisant le groupe dimenthylphosphonate comme auxiliaire chiral, nous avons obtenu par réarrangement [2,3]-sigmatropique de Wittig de l'allyloxyméthylphosphonate avec une très bonne diastéréosélectivité (de = 92 %).
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28

Lessard, Maryse. "Étude de l'expression des gènes encodant les sous-unités d'intégrines alpha4 et alpha5 dans le contexte des propriétés tumorigènes et métastatiques du mélanome uvéal." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/25958/25958.pdf.

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29

Grudzinska, Joanna. "Charakterisierung der Ligandenbindung am [alpha]1-homo- [alpha-1-homo-] und [alpha]1[beta]-heterooligomeren [alpha-1-beta-heterooligomeren] Glycinrezeptor." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=976836025.

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30

Dünkel, Jens. "Enantioselektive katalytische Hydrierung von [alpha]-Acetamidozimtsäure [Alpha-Acetamidozimtsäure] zu [alpha]-Acetamidophenylalanin [Alpha-Acetamidophenylalanin] mit Hilfe polymerfixierter feststoffgeträgerter Rhodium(I)-Komplexe." [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB11514085.

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31

Thimann, Wolfgang. "Synthese und Cyclisierung von [alpha]-Aminocarbohydroximsäureestern [Alpha-Aminocarbohydroximsäureestern]." [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=959548890.

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32

Shakya, Sagar Raj. "Studies on alpha,alpha-disubstituted bicyclic beta-lactams." Thesis, University of Ottawa (Canada), 1992. http://hdl.handle.net/10393/7571.

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General Organization. This thesis contains a brief introduction to the area of $\beta$-lactam antibiotics and four other Chapters dealing with the syntheses of various 6-methoxy $\beta$-lactams. Due to the tremendous level of activity in this area the introductory literature material is presented in an illustrative approach rather than a comprehensive approach. Literature surveys were carried out using Chemical Abstracts from 1982 to February 1992. Experimental details are given at the end of each Chapter. Compounds in the schemes which did not lead to desired conclusion were not completely characterized; $\sp1$H NMR and other spectral data whenever available are given in the Experimental section. IR was not recorded in most of these cases. Elemental analyses were not performed at all, since the data from such experiments do not always represent the purity of product. Chapter 1. This section describes the development of various $\beta$-lactam antibiotics, major representative structures, mode of action and overall objectives of the research undertaken. Chapter 2. 7-Methoxy-7-ethyl and 7-methoxy-7-hydroxyethylisocephem analogs were prepared from 4-cinnamyl-3-methoxyazetidinone which was prepared in a multigram scale. This precursor can be purified simply by trituration with ether. The transformation of this monocyclic starting material to the cyclization precursor involved introduction of an additional side-chain at C-3 via. generation of anion using lithium diisopropylamide and quenching of the anion with either ethyl iodide or acetaldehyde. In the case of the hydroxyethyl side-chain oxidation with pyridinium chlorochromate, reduction with L-Selectride and silylation with tert-butyldimethylsilyl triflate was required before carrying out further manipulations. The cinnamyl group was converted to a methylene bearing a leaving group and the p-methoxyphenyl moiety on nitrogen was cleaved and a suitable acetate side-chain was introduced. The anionic annulation with CS$\sb2$ gave the desired bicyclic compounds. An optically active isocephem having a thienamycin type side-chain at C-7 and and a racemic isocephem having a methoxy group at C-7 were prepared by similar method. Chapter 3. 7-Ethyl-7-methoxycarbacephem was prepared using a rhodium carbenoid reaction starting from 4-cinnamyl-3-methoxyazetidinone. A similar method was applied to prepare an advanced intermediate for 7-hydroxyethyl-7-methoxycarbacephem. Chapter 4. 6-Methoxy-PS 5 synthesis was attempted which was found to be unstable. The cyclization was carried out applying the rhodium carbenoid methodology. The cyclization precursor was obtained using nitroaldol condensation starting from an aldehyde which was prepared from 4-cinnamyl-3-methoxyazetidinone. Chapter 5. Syntheses of 6-methoxy-1-methyl-PS 5 analogs were attempted starting from 3-ethyl-3-methoxy-4-methylcinnamylazetidinone. The introduction of 1-methyl group involved the reduction of a suitable $\alpha,\beta$-unsaturated ester obtained via. palladium catalyzed carbonylation reaction.
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33

Petzold, Verena. "Aufbau und Evaluierung eines Chemilumineszenz-Immunoassays zur Bestimmung von 17[alpha]-Hydroxyprogesteron [17-alpha-Hydroxyprogesteron] im Serum mittels eines 7[alpha]-biotinylierten 17[alpha]-Hydroxyprogesteron-Tracers [7-alpha-biotinylierten 17-alpha-Hydroxyprogesteron-Tracers]." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=962102296.

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34

Böhm, Stephan. "alpha-Phycoerythrocyanin." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-58729.

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35

CINTRAT, JEAN-CHRISTOPHE. "Acetals alpha-stanniques et 2-stannyl oxazolidines precurseurs d'organostanniques alpha-oxygenes et alpha azotes chiraux." Nantes, 1995. http://www.theses.fr/1995NANT2083.

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Une nouvelle methode d'acces a des precurseurs de carbanions alpha-heterosubstitues chiraux est proposee apres avoir considere les differents modes d'acces et la stabilite chimique, thermodynamique et configurationnelle de ces anions. Des acetals alpha-stanniques chiraux et des 2-stannyl oxazolidines chirales n-protegees sont obtenues par transacetalisation du diethoxymethyltributyletain par des diols de symetrie c#2 ou par des beta-aminoalcools n-sulfonyles ou n-alcoxycarbonyles enantiopurs. Leur transmetallation par le n-butyllithium dans le thf a -78c conduit a des equivalents de formylanions chiraux dont nous avons montre la stabilite configurationnelle en serie des 2-lithio oxazolidines. L'ouverture des acetals alpha-stanniques par des nucleophiles mous (organocuivreux, allyletains, enoxysilanes) en presence d'acides de lewis intervient selon un processus s#n2 anti tres majoritaire alors que les organoaluminiques conduisent a une syn ouverture. Dans le cas des 2-tributylstannyl oxazolidines des reactions analogues ont ete observees. En serie n-tosylee seuls les isomeres e reagissent et conduisent a un seul diastereoisomere alors qu'en serie n-alcoxycarbonylee, les deux isomeres sont reactifs et conduisent a des bilans stereochimiques comparables. Ces resultats sont interpretes par l'intervention d'un mecanisme concerte anti dans le premier cas et par le passage par un intermediaire n-alcoxycarbonyl iminium dans le second cas. La transmetallation des organostanniques alpha-alcoxyles obtenus conduit aux alpha-alcoxylalkyllithiums avec retention de configuration mais les premiers essais realises en serie alpha-azotee ont pour l'instant ete infructueux
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36

Luonteri, Elina. "Fungal [alpha]-arabinofuranosidases and [alpha]-galactosidases acting on polysaccharides /." Espoo : Technical Research Centre of Finland, 1998. http://www.vtt.fi/inf/pdf/publications/1998/P371.pdf.

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37

Hauser, Melanie R. "Selective calcium binding by alpha-hydoxyketones and alpha-hydroxyamides /." view abstract or download file of text, 2006. http://proquest.umi.com/pqdweb?did=1251854561&sid=3&Fmt=2&clientId=11238&RQT=309&VName=PQD.

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Thesis (Ph. D.)--University of Oregon, 2006.
Typescript. Includes vita and abstract. Includes bibliographical references (leaves 115 - 121). Also available for download via the World Wide Web; free to University of Oregon users.
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38

Owens, Joanna. "Regulation of peroxisome proliferator-activated receptor-alpha (PPAR#alpha#)." Thesis, University of Surrey, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341337.

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39

Tripe, Peter. "Alpha decay and alpha elastic scattering by heavy nuclei." Master's thesis, University of Cape Town, 1993. http://hdl.handle.net/11427/17411.

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Includes bibliographical references.
A simple three parameter cluster model has previously been developed by Buck, Merchant and Perez to successfully describe alpha decay half lives for more than 400 nuclei. An important feature of this model is that it envisages preformed (preformation factor, P=1.0) alpha particles in the parent nuclei to be moving in orbits with a large value of a global quantum number, G. The discontinuity in decay half-lives at the N=l26 neutron shell closure is then naturally explained by an increase of G as the alpha particle is forced into a higher orbit by the shell closure. We consider alternative approaches to this model and extend it to consider different values of P, and different changes in G at shell closures. We find the original approach of Buck et al., a radius fit with ΔG=2, is still the most successful, but that a potential fit with ΔG=4 turns out to be competitive, lending support to the suggestion that the proton shell closure is also felt. We have also analysed low energy (24.7MeV) scattering of alpha particles from a number of heavy nuclei in an attempt to find a common set of potential parameters that adequately reproduces both the decay and scattering data. Although not completely successful in this attempt, we find that the potential parameters obtained in the decay calculations provide a good first guess at the scattering potential parameters. The above analysis constrains P to the range 0.01≤P≤0.1, with the value of P=1.0 not ruled out.
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40

Bonne, Damien. "Nouvelles réactions multicomposant utilisant l'acide alpha-substitué alpha-isocyanoacétique." Paris 11, 2006. http://www.theses.fr/2006PA112162.

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Nous avons réussi à exploiter la réactivité de l'acide alpha-substitué alpha-isocyanoacétique et plus exactement l'équilibre oxazolone–5-hydroxyoxazole pour la synthèse de dipetpides. Nous avons également montré que les MCRs, connues essentiellement pour la génération de librairies de composés, pouvaient être employées en tant qu'outil synthétique pour réaliser des transformations fondamentales. En effet une méthode d'homologation oxydante d'aldéhydes en amides avec une extension d'un atome de la chaîne carbonée a été développée par l'utilisation du même acide alpha-substitué alpha-isocyanoacétique. Cette différence dans le chemin réactionnel est essentiellement due à substitution alkyle ou aryle en alpha de l'isonitrile. Nous avons également développé deux nouvelles réactions multicomposant : une synthèse à quatre composants de furopyrrolones basé sur la réactivité unique de l'isocyanoacétate de méthyl portant un groupement 4-nitrophényl en alpha. Une synthèse à trois composant de 4-imino-4H-3,1-benzoxazines utilisant le 2-isocyanobenzamide comme composant bifonctionnel. Ce travail de thèse montre la puissance et le potentiel des réactions multicomposant utilisant un isonitrile (IMCRs) qui utilisent toutes des produits de départs commerciaux ou facilement accessibles. Nous avons aussi démontré aussi la subtilité et le potentiel de la chimie que nous avons rencontré puisque les isonitriles employés dans les trois premiers chapitres possèdent des structures très voisines mais aboutissent à des structures complètement différentes lorsqu'ils sont employés dans des réactions multicomposant
We have shown that potassium isocyano acetic acid derivatives can efficiently participate in Ugi 4CR/five centers reaction leading to the formation of dipeptides or tripeptides. We have also developed a novel method for oxidative homologation of aldehyde to amide using the same isocyano acetic acid derivative. The reaction is realized under very mild conditions using readily accessible reagents. While multicomponent reaction (MCR) is gaining popularity for creating the structural complexity and diversity, we demonstrated herein that research on MCR can also lead to the discovery of new fundamental transformations. The difference in the reaction pathway using isocyanoacetic acid derivatives is essentially based on the substitution (alkyl or aryl) in the alpha position of the isonitrile. We also work in the development of two new multicomponent reactions:A four-component sythesis of furopyrrolones based on the unique reactivity of an isocyanoacetate bearing a 4-nitrophenyl group in the alpha position. . A three-component synthesis of 4-imino-4H-3,1-benzoxazines exploiting the dual reactivity of 2-isocyanobenzamide derivatives. The work we have done show the power and potential of isocyanide-based multicomponent reactions (IMCRs). It is important to say that the chemistry we have been dealt with is also very subtle: the isonitriles employed in the three first chapters have very similar structures but the scaffolds accessible by the MCRs we developed are completely different. The four processes we developed during the last three years are quite efficient in terms of yield and simplicity of operation. They are therefore very useful tools for synthetic chemists
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41

Lensen, Nathalie. "Synthese d'aldehydes alpha hydroxyles chiraux et alpha amines chiraux." Paris 6, 1992. http://www.theses.fr/1992PA066227.

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Ce travail decrit la synthese diastereoselective de deux synthons chiraux: les aldehydes alpha hydroxyles et alpha amines. Pour cela nous avons utilise le glyoxal, produit commercial et tres bon marche. La dessymetrisation directe a l'aide d'une diamine chirale possedant un axe de symetrie d'ordre deux, a permis d'obtenir les monoimidazolidines du glyoxal. L'addition d'organolithiens, suivie de benzoilation permet l'obtention des aldehydes alpha hydroxyles proteges avec un tres bon exces diastereoisomerique. L'ajout des memes diamines chirales a des monohydrazones du glyoxal, permet l'introduction de la fonction azotee ainsi que de la chiralite. L'addition d'organomagnesien dans le toluene a conduit a un seul diastereoisomere, grace a un etat de transition chelate. En revanche, l'addition d'organolithien dans le tetrahydrofuranne conduit a l'autre diastereoisomere grace a un controle sterique de la reaction. Afin d'acceder aux aldehydes alpha-amines, nous avons de plus mis au point une technique performante d'hydrogenolyse de liaison n-n d'hydrazines tri-substituees et non activees, ceci grace a l'utilisation de nickel de raney active par sonochimie. De plus, toutes ces transformations s'effectuent sans epimerisation. Ces syntheses permettent de plus la recuperation integrale de l'inducteur chiral
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42

Baum, Matthew Philip. "ALPHA DOGS: Hunting for Alpha Among Value Mutual Funds." Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/192264.

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43

Godbout, Cédrickx. "Développement d'une nouvelle méthodologie pour la préparation stéréosélective d'acides aminés [alpha]-alkylés et [alpha,alpha]-dialkylés." Mémoire, Université de Sherbrooke, 2002. http://savoirs.usherbrooke.ca/handle/11143/4511.

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Le premier chapitre de ce mémoire décrit la synthèse générale d'alcools allyliques di et trisubstitués qui sont obtenus de deux façons : [1] Par addition d'un lithien vinylique à un aldéhyde chiral dérivé de la (-)-menthone ; [2] Par réduction hautement stéréosélective d'une énone chirale. Ces alcools allyliques sont d'une grande importance puisqu'ils constituent les intermédiaires clés de notre stratégie de synthèse conduisant aux acides [alpha]-aminés.Le deuxième chapitre décrit l'utilisation de ces systèmes allyliques disubstitués dans une réaction de Mitsunobu en utilisant l'acide hydrazoïque comme nucléophile, ceci afin d'introduire régio et stéréosélectivement la portion aminée. La construction expéditive de centres stéréogéniques tertiaires possédant un atome d'azote est rendue possible, comme en témoigne la synthèse d'un intermédiaire avancé conduisant à la (-)-coniine, un alcaloïde naturel.Le troisième chapitre traite du réarrangement de Curtius effectué sur des intermédiaires avancés possédant un acide carboxylique adjacent à un centre chiral tertiaire ou quaternaire. Ce réarrangement procède avec rétention complète de la stéréochimie et permet de synthétiser des précurseurs d'acides aminés [alpha]-substitués ou [alpha, alpha]-disubstitués optiquement purs. De plus, cette stratégie permet d'atteindre les deux énantiomères à partir d'un intermédiaire commun. De cette façon, la (+) et la (-)- t -leucine, ainsi que la (+) et la (-)-methylvaline sont synthétisées pour démontrer la viabilité de cette méthodologie.
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44

Godbout, Cédrickx. "Développement d'une nouvelle méthodologie pour la préparation stéréosélective d'acides aminés [alpha]-alkylés et [alpha,alpha]-dialkylés." Sherbrooke : Université de Sherbrooke, 2002.

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45

LEROUX-ANDREN, JULIETTE. "Contribution a l'etude des composes organophosphores. Nouvelles voies d'acces aux alpha-dehydro-aminoacides heterocycliques et aux cetones alpha-ethyleniques et alpha,alpha-dieniques." Rennes 1, 1990. http://www.theses.fr/1990REN10003.

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L'objectif de ce travail etait d'explorer les possibilites offertes par les phosphorannes porteurs d'un groupement nucleofuge en gamma, delta, epsilon du phosphore pour la synthese d'alpha-dehydro-aminoacides heterocycliques et de cetones alpha-ethyleniques et alpha,alpha-dieniques. Le n-carbomethoxy oxamate d'ethyle est un bon precurseur d'alpha-dehdro-aminoacies proteges. Il a ete engage dans une reaction de n-alkylation avec des sels de phosphonium gamma ou delta-halogenes et un ylure beta-cetonique gamma-halogene. Cette alkylation, suivie d'une condensation de wittig intramoleculaire conduit aux derives proteges d'alpha-dehydro-aminoacides heterocycliques. L'etude de la condensation des beta et gamma-lactones sur les ylures du phosphore a permis d'acceder a une serie de phosphorannes beta-cetoniques delta ou epsilon-hydroxyles. La reactivite de ces composes vis-a-vis des aldehydes et des cetones conduit a l'obtention de cetones alpha-ethyleniques gamma-hydroxylees et alpha,alpha-dieniques. L'etude de leur stabilite thermique a permis de definir une nouvelle voie d'acces aux cetones alpha-ethyleniques par une reacton d'extrusion d'oxyde de triphenylphosphine. La mise au point d'une methode generale d'acces aux phosphorannes beta-cetoniques delta-hydroxyles permet d'elargir les possibilites de cette methode
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46

Andaç, Zeynep. "Rekombinante Herstellung und Charakterisierung des E3-Fragments sowie seiner einzelnen Module LG4 und LG5 aus der Laminin-1-[alpha]1-Kette [Laminin-1-alpha1-Kette]." [S.l. : s.n.], 2002. http://www.diss.fu-berlin.de/2002/212/index.html.

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47

Chahrour, Ghada. "Estrogen-related receptor [alpha] (ERR[alpha]), estrogen receptor [alpha] (ERA[alpha]) and erbB-E (Neu) crosstalk in a mouse model of human breast cancer." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80237.

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Estrogen (17-beta estradiol) and its receptor (ERalpha) have important physiological roles and are well implicated in human breast cancer, but less is known about the function of estrogen-related orphan nuclear receptor alpha (ERRalpha). The close kinship between ERalpha and ERRalpha and the existing, but yet to be fully characterized, interplay between ERalpha and erbB2 (Neu) protooncogene signaling pathways, suggest that ERRalpha may also play a significant role in breast cancer. Thus, the focus of the current study was to determine the extent of ERRalpha cross talk with ERalpha, its physiological role, as well as its possible implication in erbB2-driven mammary tumorigenesis. Using a well characterized erbB2 mouse model of human breast cancer where tumorigenesis occurs following a long latency period, we generated ERRalpha deficient mice (ERRalphaKO) expressing an activated erbB2 oncogene.
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48

Sykes, Karen L. Vestergaard. "Effect of 6[alpha]-methyl-17[alpha] hydroxyprogesterone acetate on uterine secretion of prostaglandin (PG) F₂[alpha] and luteal sensitivity to exogenous PGF₂[alpha] /." This resource online, 1995. http://scholar.lib.vt.edu/theses/available/etd-02132009-171106/.

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49

Gabi, Ahmed. "Contribution à l'étude de l'émission alpha et la diffusion élastique alpha-alpha à l'aide d'un même formalisme." Bordeaux 1, 1985. http://www.theses.fr/1985BOR10510.

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Ce travail porte sur l'identification entre les expressions generales de l'emission alpha et la largeur de la diffusion elastique alpha. L'interaction alpha-alpha est decrite par un potentiel a deux corps de forme gautienne ou de woods-saxon. Ce potentiel donne correctement l'energie et la largeur d'emission de l'etat fondamental de #8be et les dephasages sur l = 0,2,4 et 6
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50

Lausen, Jörn. "Einfluss Diabetes-assoziierter Mutationen im Transkriptionsfaktor HNF4[alpha] [HNF4-alpha]." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963191071.

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