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Building the New American Nation: The U.S. Army and Economic Development, 1787-1860
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This dissertation examines the Army's integral role in the early American political economy. Notwithstanding its small size, the Army proved to be a powerful instrument for promoting economic expansion and guiding the pattern and direction of development. The Army spurred development through two lines of activity: first, the traditional application of coercion and, second, by providing public goods that neither private actors nor state governments could supply. Considering the Army leads me to reconceptualize the early American state as a bifurcated entity: a state of the periphery, dominated by the Army, and a state of the center, in which the Army still influenced economic development but other public institutions also performed key development functions.
The Role of Striatal Neuropeptides on Glutamate and Methamphetamine-Induced Neurotoxicity in the Murine Brain
ABSTRACT THE ROLE OF STRIATAL NEUROPEPTIDES ON GLUTAMATE AND METHAMPHETAMINE-INDUCED NEUROTOXICITY IN THE MURINE BRAIN by Lauriaselle Afanador Adviser: Dr. Jesus A. Angulo
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The rising worldwide epidemic in addiction to methamphetamine (METH) and the well-documented neurological detriments it causes emphasizes the importance of elucidating the mechanisms by which METH causes widespread and prolonged damage. Also, METH's pathophysiology resembles a number of neurodegenerative diseases. Therefore a better understanding of the mechanisms involved would provide more effective therapeutic targets for the treatment of these neurological disorders.
METH toxicity is a complex interplay of various factors however a number of necessary components have been identified such as dopamine overflow (DA), glutamate signaling, and oxidative stress. Although METH-induced DA overflow is the initiating event, it is not the direct cause of damage. Oxidative stress is thought to be the mediator of METH toxicity and nitric oxide (NO) as a contributor.
We have found that substance P (SP) exacerbates METH-induced NO. Inhibition of SP signaling mitigated NO synthesis and conferred protection. Considering the role SP is playing in METH toxicity we wanted to investigate the role that other striatal neuropeptides play in these events, notably the inhibitory peptides neuropeptide Y (NPY) and somatostatin (SST).
We hypothesized that SP is augmenting NMDA signaling and thus magnifying NO production. Whereas NPY and SST would serve as a counteracting force thus dampening oxidative stress and conferring protection. Overall, our data demonstrated that SP does augment NMDA signaling as inhibition of the neurokinin-1 receptor (NK-1R) decreased NMDA-induced striatal cell loss. We found that SP was potentiating NMDA-induced NO production. Although the predominant source of NO was the inducible form of nitric oxide synthase (NOS).
In support of our hypothesis, NPY and SST proved to attenuate NO. Also, they were protective from METH-induced cell death although SST failed to protect DA terminals. However, an agonist for the NPY-Y2 receptor was successful in maintaining DA terminal viability. Of interest is that neither NPY nor SST modulated NMDA-induced NO or cell loss suggesting that their protective mechanism does not include modulation glutamate signaling within the striatum.
PHOTOPHYSICS AND CATALYSIS OF PORPHYRINOIDS
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Organic nanoparticles (ONP) of metalloporphyrins can be versatile catalysts for the selective oxidation of alkenes and other hydrocarbons. Herein, we report the catalytic activity of ONP of 5,10,15,20-tetrakis-[4-(1'H,1'H,2'H,2'H-heptadecafluorodecane-1-thiol)-2,3,5,6-tetrafluorophenyl] porphyrinato iron(III), Fe(III)TPPF84, and 5,10,15,20-tetakis-(2,3,4,5,6-pentafluorophenyl) porphyrinato manganese(III), Mn(III)TPPF20, for cyclohexene oxidation using molecular oxygen as an oxidant in water under ambient conditions. While the solvated metalloporphyrins catalytically oxidize alkenes to the corresponding epoxide in halogenated solvent with a modest turn-over numbers (TON), 10-30 nm ONP of these metalloporphyrins have enhanced catalytic activity with up to a 4-fold greater TON and yields only allylic oxidation products. These ONP catalytic systems facilitate a greener reaction since ca. 89% of the reaction medium is water, molecular oxygen is used in place of man-made oxidants, and the ambient reaction conditions require less energy. The enhanced catalytic activity of these ONP is unexpected because the metalloporphyrins in the nanoaggregates are in the close proximity and the TON should diminish by self-oxidative degradation. The fluorous alkanes in Fe(III)TPPF84 stabilize the ONP towards self-oxidative degradation. Sequential dipping of indium-tin-oxide electrodes into solutions of tetra cationic porphyrins and tetra anionic polyoxometalates results in the controlled formation of nm thick films. The potential applications of these robust films on electrodes range from catalysts to sensors. This chapter focuses on the electrochemistry of the multilayered films where it is found that the oxidation and reduction potentials of each species remain largely the same as found in solution. Photophysical properties of Porphyrinoids bearing four rigid hydrogen bonding motifs on the meso positions, self-assembled into a cofacial cage with four complementary bis(decyl)melamine units in dry solvents are presented here. Self-assembly was investigated by NMR spectroscopy, dynamic light scattering, and atomic force microscopy. The phototphysical properties of the cage formation involve the measurement of their absorption and emission spectra and the fluorescence life time in dry THF. The hydrocarbon chains on the bis(decyl)melamine mediate the formation of nanofilms on surfaces as the solvent slowly evaporates. A systematic study of the photophysical properties of a series of porphyrinoids is presented. The role of the location of a heavy atom in shunting the excited state from the singlet to the triplet manifolds is compared for three cases. It is well known that Pt(II) metalloporphyrins do not fluoresce. For meso pyridyl porphyrins, the fluorescence quantum yield decreases as the number of coordinatively attached Pt(II) complexes increase from 0-4, but the tetracoordinated species retains about 30% of the fluorescence. Covalently attaching a heavy metal complex e.g.Pt(II) complex to the macrocycle by an organometalic bond at the peripheral meso position causes greater than a 20-fold decrease in fluorescence quantum yield and may enhance some internal conversion to the ground state. For comparison, the fluorescence quantum yield decreases somewhat as the number of pyridyl groups on the meso positions increase 0-4. We also evaluate the photophysical properties of a series of porphyrins with nitro groups on the β pyrrole position and on the meso phenyl group, which also quenches the fluorescence. These studies bear on the use of metal ions to enhance the photophysical properties of these dyes as photodynamic therapeutics and for supramolecular systems, while the nitrated macrocycles have potential application in non linear optics. The photophysical properties of non-hydrolysable tetra- thioglycosylated conjugates of chlorin (CGlc4), isobacteriochlorin (IGlc4) and bacteriochlorin (BGlc4) and core F20 platforms are reported here. These studies involve the measurement of absorption and emission spectra, fluorescence quantum yield, singlet oxygen quantum yield, and singlet state life time in three different solvents: phosphate buffer saline (PBS), ethanol, and ethylacetate. Compared to the porphyrin in PBS, CGlc4 has a markedly greater absorbance of red light near 650 nm and a 6-fold increase in fluorescence quantum yield; whereas IGlc4 has broad Q bands and a 12-fold increase in fluorescence quantum yield. Since IGlc4 CGlc4 very slowly bleach, these properties may enable their use as fluorescent tags to track biological processes. BGlc4 has a similar fluorescence quantum yield to PGlc4, (<10%), but the lowest energy absorption/emission peaks of BGlc4 are considerably red shifted to near 730 nm with a nearly 50-fold greater absorbance, which may allow this conjugate to be an effective PDT agent. The excited state life time of these conjugates ranges from 3-11 ns. The radiative time constant for IGlc4 is 20 fold less while non-radiative time constant is 2 fold more than BGlc4, indicates that IGlc4 has greater potential to form triplet state via inter system crossing, and so can serves as a better PDT agent. The uptake of CGlc4, IGlc4 and BGlc4 derivatives into cells such as human breast cancer cells MDA-MB-231 and K:Molv NIH 3T3 mouse fibroblast cells can be observed at nM concentrations. Photobleaching under these conditions is minimal.
PUBLIC EDUCATION IN THE UNITED STATES: THE PRODUCTION OF A NORMATIVE CULTURAL LOGIC OF INEQUALITY THROUGH CHOICE
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"Public Education in the United States: The Production of a Normative Cultural Logic of Inequality Through Choice" is a historically informed ethnography that examines how choice emerged in the post-Brown v. Board of Education era as a key principle of reform and management in public education and became central to how rights, freedom, and citizenship were structured, constrained, and imagined. Scholarship within education studies has identified choice as a predicament of neoliberalism as privatization. Yet as my research examines, the inequalities associated with privatization mechanisms like charter schools are an exaggerated indexical representation of a much deeper and older problem. My research extends the historical trajectory through which we understand neoliberal restructuring and traces the ideological and material contours of a post-Brown realignment between the state, the structuring of rights, and the market--a realignment that extends beyond the realm of the private. This dissertation is based on eighteen months of ethnographic fieldwork in New York City's Community School District (CSD) 3, one of the most racially and economically diverse districts in the nation's largest school system. CSD 3 is also one of the most segregated districts in New York City and one of the districts that provides the most choice-based programs and policies. In my ethnography, I examine the ways that low-income and middle-income parents navigate and negotiate selecting a public non-charter elementary school for their child. I trace how situated claims to universal rights as choices facilitate the continuance of a tiered citizenship and the production of what I term a "normative cultural logic of inequality." My research interrogates how this logic narrates inequality in education as resulting from "bad" yet "fair" choices that are qualified by a lack of individual initiative, informed decisions, and capacities of parental care. My findings suggest that rather than these explanations, the differential accumulation of living in what Ruth Wilson Gilmore has termed the "forgotten" or "abandoned places" of a racial state are central to understanding how similar desires---of wanting the very best for one's child---result in very different outcomes.
An empirical re-evaluation of the effects of education in nonmarket production
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Abstract AN EMPIRICAL RE-EVALUATION OF THE EFFECTS OF EDUCATION IN NONMARKET PRODUCTION by CHRISTIE AGIOUTANTI Adviser: Distinguished Professor Michael Grossman This paper tests the empirical validity of the productive efficiency hypothesis effect of education in the nonmarket sector via consumption expenditure patterns, which is essentially the foundation in Michael's (1972) behavioral model. Under the assumption of factor and commodity neutrality, the education effect is expected to be positive for luxuries, negative for necessities and zero for market goods inputs whose income elasticity is equal to one. Much of the innovation of this paper primarily stems from a preliminary and broad attempt to update Michael's empirical work, while focusing on the demand for inputs in the production of "good health", the incorporation of both grouped and individual observations on consumer expenditures household data as an additional comparison tool, inclusion of all four geographical regions and allowing for zero value market good outlays. By and large, the empirical analysis of this study fails to support the predicted qualitative relationship between income and education elasticities, regardless of sample classification and item categorization. Consequently, it rejects the accuracy of productive efficiency hypothesis in the neutrality framework. Whether these findings are the byproduct of the limitations set by the theoretical model, the type and idiosyncratic nature of the dataset used or by the econometric approach employed, the effect of education on household productivity remains a puzzle and a topic that requires more rigorous investigation. "The most important of all capital is that invested in human beings." Alfred Marshall
"I Shall not Fear:" Secure Attachment to G-d as a Buffer against Anxiety.
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Religion has a long and mixed history in the field of psychology. Historically, some leading figures in the field viewed religion as a source of neuroses and poor mental health; others saw a more positive spiritual resource. Recently, empirical data on religion and mental health has proliferated. There is now consensus that religion is associated with lower depression. However, the link between religion and anxiety is less clear-cut. This paper proposes that a) religion can have exacerbating or alleviating effects on anxiety depending on which aspect of religion is being studied and b) the primary religious variable that affects anxiety levels is attachment to G-d. Utilizing the `safe haven' attachment function, people with a secure attachment to G-d seek Him when they are stressed. The anxiolytic benefit of seeking an omnipresent secure attachment figure should lead to lower general levels of anxiety. Hypotheses were explored in a series of three studies. Study One examined which aspects of religion are related to anxiety using correlational self-report methods. Hierarchical multiple regressions supported the hypothesis that attachment to G-d was of primary importance in predicting anxiety levels. In addition, positive and negative aspects of religion were differentially correlated with anxiety, as predicted. The process through which G-d attachment relates to anxiety was experimentally explored in Study Two. Participants were exposed to a stressful situation (electric shock threat), and their implicit tendency to seek G-d was measured. Results were surprising: explicitly, those with secure G-d attachment reported a greater tendency to seek G-d when stressed, but those with highly avoidant G-d attachment were the only ones to demonstrate an implicit tendency to seek G-d. Study Three further probed this association by measuring the calming effects of a G-d prime. Stress was induced in all participants while anxiety was measured (physiologically and via self-report). ANOVAs demonstrated that securely G-d attached participants primed with religious as opposed to neutral sentences experienced greater reductions in anxiety over time. Overall, this research clarified the different ways in which religion might relate to anxiety and elucidated some exact mechanisms through which religion buffers against anxiety.
Dopamine-glutamate interaction in the actions of typical antipsychotic drugs
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Typical antipsychotic drugs (APD) are currently the most effective psychoactive agents for the treatment of schizophrenia. Studies suggest that besides their conventional action of blocking dopamine (DA) D2 receptors, these drugs also interact with glutamatergic N-methyl-D-aspartate (NMDA) receptors. In addition, blockade of DA D2 receptors is believed to result in DA cell depolarization block (DB) and movement disorders (catalepsy) in animals. Since it has been hypothesized that drug's antipsychotic potency may be predicted by its ability to produce DB and catalepsy, using CD rats in behavioral, microdialysis and receptor binding studies we investigated whether typical APD induce DB and catalepsy though action on the dopaminergic system, glutamatergic system, or through the interaction between the two systems. Focus of this project was on striatum (STR) and frontal cortex (FC), two brain regions implicated in the DA-glutamate interplay. Our behavioral results show that haloperidol, a potent APD and postsynaptic DA D2 receptor blocker is a strong catalepsy inducer. Receptor binding study showed that chronic administration of this drug caused a decrease in maximal binding at the NMDA receptors in STR and FC but no significant changes in the DA D2 receptor densities were seen in the two brain areas. In contrast, metoclopramide, another DA D2 receptor blocker but not an APD, within the therapeutic doses (5 mg/kg-10 mg/kg) did not produce catalepsy in experimental animals. The maximal binding parameters for DA D2 and NMDA receptors in STR and FC after repeated administration of metoclopramide were significantly elevated as compared to haloperidol. However, when animals were pre-treated with metoclopramide (10 mg/kg) it sensitized the brain to haloperidol and enhanced catalepsy. Additionally, our receptor binding studies showed that psychotomimetic agents, PCP and ketamine that cause schizophrenia-like symptoms have several-fold higher binding affinity at NMDA receptors as compared to DA D2 receptors, indicating that pharmacological effect of these drugs may be mainly mediated by blockade of NMDA receptors. Finally, studying the neurochemical mechanism for DA cell DB we saw a decrease in striatal DA release after chronic cocaine treatment compared to controls. In a series of follow-up experiments we compared the effect of low dose (0.5 mg/kg) haloperidol and high dose (3.0 mg/kg) haloperidol by acute injection to the chronic cocaine treated rats and to the control animals. Low dose haloperidol significantly increased straital DA release compared to respective controls, while the high dose haloperidol significantly reduced it compared to the low dose. On the other hand, high dose haloperidol drastically increased striatal DA release in chronic cocaine-treated rats compared to controls. These results suggest that the mechanism for catalepsy is based on the concurrent DA D2 receptor antagonism and activation of glutamatergic NMDA transmission. Similarly, the mechanism for DA cell DB is mediated through blockade of dopaminergic D2 receptors and stimulation of NMDA receptors. Thus, catalepsy as well as antipsychotic activity appears to be mediated through modifications of dopaminergic and glutamatergic transmissions.
Fabrication of Quantum Dot Encoded Silica Beads for High-throughput Screening Applications
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The focus of this research is on the development of optically barcoded silica gel microbeads, synthesized to be used in high throughput screening platforms, using suspension methods for bead synthesis developed specifically for rapid gelation. In suspension methods for particle manufacture, precursor droplets are first formed in a continuous phase immiscible with the droplet phase. The droplets are then solidified into particles. Silica is chosen as the bead material because it can very easily be functionalized to anchor probe molecules which is necessary to function as a capture element in high throughput screening applications. The optical code embedded into the microbeads consists of the spectral signature (the emission spectrum) of a collection of luminescent species. In particular, for this study, multicolor semiconductor nanocrystals or quantum dots (QDs) are used. Each type of QD emits electromagnetic waves at a set wavelength (color), and sets of QDs will be incorporated in differing quantities to form the code. The encoding QDs are dispersed in the pre-gel droplet phase, and are surface functionalized so as not to partition in the continuous phase. In this way, the QDs are effectively trapped in the droplets as they gel to microbeads, which allows for a quantitative loading necessary for optical coding. In this study, the suspension process for encoded silica bead production is implemented using a batch stirring method for forming the emulsion, and a flow-focusing microfluidic device. The later is used to generate uniformally sized droplets of the pre-gel phase, thus insuring a monodisperse size distribution that is useful for high throughput screening platforms. The gelation of the silica precursor droplets uses an amine catalyst as an accelerant, and thus eliminates the post-production necessary in existing methodologies for obtaining silica beads. Confocal laser scanning microscopy (CLSM) is used to record the spatial distribution of the nanocrystal fluorescence in the beads and the emission spectra (the barcode). Two colors of QDs were used to create a prototype barcode, and Forster Resonance Energy Transfer (FRET) between these colors was used in addition to the spatial distribution of the fluorescence to infer the aggregation of the nanocrystals in their new silica gel environment. A comparison of the photoluminescence (PL) profiles of the barcoded silica beads demonstrate that indeed resonant energy transfer is occurring, and the crystals do aggregate. FRET shifts in the PL profiles can be attributed to poor dispersability issues in the precursor solution and can in some instances- due to extent of unfavorable conditions for the surface molecules of QDs with the solvent- limit our ability to generate a full compliment of barcodes. Untimely ionization of catalyst, and degree of which, and poor solvability of hydrophylically surface functionalized nanocrystals leads to their poor performance as entrapped luminescing signals.
SYSTEMATICS AND EVOLUTION OF THE Ronnbergia ALLIANCE (BROMELIACEAE): HISTORY OF DISJUNCT DIVERSIFICATION IN THREE BIODIVERSITY HOTSPOTS OF THE NEOTROPICS
Julian Aguirre Santoro
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The systematics, biogeography and evolution of the “Ronnbergia Alliance,” a nested lineage within the Core Bromelioideae, were investigated. In the first chapter, the phylogenetic relationships of the Ronnbergia Alliance were reconstructed using three chloroplast and three nuclear DNA sequence markers in combination with a wide species sampling across the Core Bromelioideae and a nearly complete species-level sampling of the five species complexes that likely comprise the Ronnbergia Alliance. The analysis indicates that the Ronnbergia Alliance is a robust monophyletic group sister to the remaining Core Bromelioideae, and it is composed by species of the polyphyletic genera Aechmea, Hohenbergia and Ronnbergia. The first of main lineage within the Ronnbergia Alliance, here called the Pacific Clade, contains species of that occur exclusively in the forests of southern Central America to northwestern South America. The second clade, called the Atlantic Clade, contains species mostly limited to the central corridor of the Atlantic Forest and the Greater Antilles. The combination of apically spreading tubular corollas and unappendaged ovules are diagnostic for the Ronnbergia Alliance, whereas flower size, corolla tube length, and petal pigmentation are important characters to differentiate the Pacific and Atlantic Clades. A new taxonomic reorganization and synopsis for this clade was proposed in the second chapter. Here, all the species of the Pacific Clade were placed in Ronnbergia, whereas the species of the Atlantic Clade were relocated in the resurrected genus Wittmackia. In the third chapter, a complete taxonomic revision of the Caribbean clade of Wittmackia was conducted. In the fourth chapter, the biogeographic history and evolutionary rate dynamics of the Ronnbergia Alliance were analyzed. These analyses showed that one vicariant event that separated Ronnbergia from Wittmackia in South America, and a later long-distance dispersal event allowed the separation of Wittmackia between the Atlantic Forest and Jamaica. Although the evolutionary rate dynamics remained constant during the diversification of Ronnbergia, these rates were heterogeneous during the radiation of Wittmackia. This is the first species-level approach that combines phylogenetic, ecological, geographic and morphological information to reveal fine-scale processes that shaped the evolution of highly diverse lineages of Bromeliaceae.
COMPUTATIONAL STUDIES ON INTERACTION BETWEEN SOME RECEPTORS AND LIGANDS OF TRANSFORMING GROWTH FACTOR-BETA SUPERFAMILY: DESIGN OF INHIBITOR(S) TO PROMOTE OSTEOGENESIS
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Transforming growth factor beta (TGF-β) superfamily members execute distinct and intricate roles in numerous biological events such as cell growth, differentiation, embryogenesis, immune responses, and morphogenesis etc. Diverse cellular responses are instigated by binding of these superfamily members to specific transmembrane serine/threonine kinase receptors on the cell surface and thereby activating specific pathways. As a result receptor-regulated Smad proteins are phosphorylated, followed by their complex formation with Co-Smad that together translocates into nucleus and leads to the initiation of transcription of target genes. Bone morphogenic proteins (BMPs), activins, Inhibins are the most important members of TGF-β family. When they exert their biological activity, they are sternly regulated by extracellular antagonists such as noggin, follistatin, CV2, and so forth that are expressed in close temporal and spatial proximity. Blocking these antagonists' interaction with their target receptor proteins helps to promote their respective biological responses when needed. This work is an attempt to use the current understanding of some of the receptors and ligands of TGF- superfamily members, namely BMPs, activins and inhibins and their antagonists such as noggin, follistatin, and crossveinless 2 (CV2) interactions through the analysis of their available complex structures to design small molecular inhibitors with an ultimate goal of promoting their respective biological responses. Noggin is a major natural extracellular antagonist to BMPs which binds to BMPs and blocks binding of them to BMP-specific receptors and thus negatively regulates BMP-induced osteoblastic differentiation. BMPs signal through heteromeric protein complexes composed of type I and type II serine/threonine kinase receptors. Preventing the BMP-2/noggin interaction will preserve free BMP-2 and enhance the efficacy of BMP-2 to induce bone formation. One part of this work is an attempt to use the current understanding of BMP-2, and its interaction with its receptors and antagonists, through the analysis of known structures in protein data bank (PDB), to design inhibitors of BMP-2/noggin interaction with the goal of lowering the dose of BMP-2 required in clinical applications to promote osteogenesis. Another TGF- superfamily member, the activin, exerts pivotal roles in male and female reproduction, and has powerful actions in growth and differentiation in various tissues. The ability of activins to assemble their receptor complex, however, is regulated by a number of extracellular binding proteins. Follistatin is one of the main inhibitors among them. Follistatin acts primarily by binding to activin and preventing its interaction with its receptor there by bio-neutralizes activin-mediated responses. Here our main hypothesis is to understand the activin interaction with its receptors and antagonist follistatin, through the available structures in PDB, to design small molecular binder that blocks activin/follistatin interaction with the goal of promoting BMP responsiveness of the cells. Crossveinless 2 (CV2), a member of Chordin family, is an extracellular modulator of BMPs which has a unique feature of having both the anti- and pro-BMP activity depending on the cellular context. The anti-BMP activity is directed by excessive dosage of CV2 that impedes the BMP-dependent differentiation of osteoblast and chondrocyte in cell culture and in certain developmental stages. Crystal Structure of BMP-2/CV2-VWC1 domain is available. Here, our main goal is to design a potential inhibitor of BMP-2/CV2 interaction to promote osteoblast differentiation leading to promotion of bone healing. We analyzed the available complex structures to identify contact region of CV2 with BMP-2. By using the binding information of BMP with its receptors from BMP-2/noggin studies, we performed virtual screening and identified several compounds that are likely to bind to CV2 and block BMP-2/CV2 interaction that may enhance the ectopic bone formation. Finally, by using the BMP-2 sequence fragments that are in contact with noggin, from the BMP/noggin complex structure, we designed several, di-, tri- and tetra-peptide combination structures and docked them onto respective binding sites on noggin with future goal to develop modified peptide mimetic compounds that may help blocking BMP/noggin binding to promote osteogenesis.