Mechanisms and molecular regulation of mammalian tooth replacement

In most non-mammalian vertebrates, such as fish and reptiles, teeth are replaced continuously. However, tooth replacement in most mammals, including human, takes place only once and further renewal is apparently inhibited. It is not known how tooth replacement is genetically regulated, and little is known on the physiological mechanism and evolutionary reduction of tooth replacement in mammals. In this study I have attempted to address these questions. In a rare human condition cleidocranial dysplasia, caused by a mutation in a Runt domain transcription factor Runx2, tooth replacement is continued. Runx2 mutant mice were used to investigate the molecular mechanisms of Runx2 function. Microarray analysis from dissected embryonic day 14 Runx2 mutant and wild type dental mesenchymes revealed many downstream targets of Runx2, which were validated using in situ hybridization and tissue culture methods. Wnt signaling inhibitor Dkk1 was identified as a candidate target, and in tissue culture conditions it was shown that Dkk1 is induced by FGF4 and this induction is Runx2 dependent. These experiments demonstrated a connection between Runx2, FGF and Wnt signaling in tooth development and possibly also in tooth replacement. The role of Wnt signaling in tooth replacement was further investigated by using a transgenic mouse model where Wnt signaling mediator β-catenin is continuously stabilized in dental epithelium. This stabilization led to activated Wnt signaling and to the formation of multiple enamel knots. In vitro and transplantation experiments were performed to examine the process of extra tooth formation. We showed that new teeth were continuously generated and that new teeth form from pre-existing teeth. A morphodynamic activator-inhibitor model was used to simulate enamel knot formation. By increasing the intrinsic production rate of the activator (β-catenin), the multiple enamel knot phenotype was reproduced by computer simulations. It was thus concluded that β-catenin acts as an upstream activator of enamel knots, closely linking Wnt signaling to the regulation of tooth renewal. As mice do not normally replace teeth, we used other model animals to investigate the physiological and genetic mechanisms of tooth replacement. Sorex araneus, the common shrew was earlier reported to have non-functional tooth replacement in all antemolar tooth positions. We showed by histological and gene expression studies that there is tooth replacement only in one position, the premolar 4 and that the deciduous tooth is diminished in size and disappears during embryogenesis without becoming functional. The growth rates of deciduous and permanent premolar 4 were measured and it was shown by competence inference that the early initiation of the replacement tooth in relation to the developmental stage of the deciduous tooth led to the inhibition of deciduous tooth morphogenesis. It was concluded that the evolutionary loss of deciduous teeth may involve the early activation of replacement teeth, which in turn suppress their predecessors. Mustela putorius furo, the ferret, has a dentition that resembles that of the human as ferrets have teeth that belong to all four tooth families, and all the antemolar teeth are replaced once. To investigate the replacement mechanism, histological serial sections from different embryonic stages were analyzed. It was noticed that tooth replacement is a process which involves the growth and detachment of the dental lamina from the lingual cervical loop of the deciduous tooth. Detachment of the deciduous tooth leads to a free successional dental lamina, which grows deeper into the mesenchyme, and later buds the replacement tooth. A careful 3D analysis of serial histological sections was performed and it was shown that replacement teeth are initiated from the successional dental lamina and not from the epithelium of the deciduous tooth. The molecular regulation of tooth replacement was studied and it was shown by examination of expression patterns of candidate regulatory genes that BMP/Wnt inhibitor Sostdc1 was strongly expressed in the buccal aspect of the dental lamina, and in the intersection between the detaching deciduous tooth and the successional dental lamina, suggesting a role for Sostdc1 in the process of detachment. Shh was expressed in the enamel knot and in the inner enamel epithelium in both generations of teeth supporting the view that the morphogenesis of both generations of teeth is regulated by similar mechanisms. In summary, histological and molecular studies on different model animals and transgenic mouse models were used to investigate tooth replacement. This thesis work has significantly contributed to the knowledge on the physiological mechanisms and molecular regulation of tooth replacement and its evolutionary suppression in mammals.

Suppression of the zero-order term in off-axis digital holography through nonlinear filtering

We present experimental validation of a new reconstruction method for off-axis digital holographic microscopy (DHM). This method effectively suppresses the object autocorrelation,namely, the zero-order term,from holographic data,thereby improving the reconstruction bandwidth of complex wavefronts. The algorithm is based on nonlinear filtering and can be applied to standard DHM setups with realistic recording conditions.We study the robustness of the technique under different experimental configurations,and quantitatively demonstrate its enhancement capabilities on phase signals.

Experimental Demonstration of H{infty} Control based Active Vibration Suppression in Composite Fin-tip of Aircraft using Optimally Placed Piezoelectric Patch Actuators

The goal of this study is the multi-mode structural vibration control in the composite fin-tip of an aircraft. Structural model of the composite fin-tip with surface bonded piezoelectric actuators is developed using the finite element method. The finite element model is updated experimentally to reflect the natural frequencies and mode shapes accurately. A model order reduction technique is employed for reducing the finite element structural matrices before developing the controller. Particle swarm based evolutionary optimization technique is used for optimal placement of piezoelectric patch actuators and accelerometer sensors to suppress vibration. H{infty} based active vibration controllers are designed directly in the discrete domain and implemented using dSpace® (DS-1005) electronic signal processing boards. Significant vibration suppression in the multiple bending modes of interest is experimentally demonstrated for sinusoidal and band limited white noise forcing functions.

Suppression of spinel formation to induce reversible thermal behavior in the layered double hydroxides (LDHs) of Co with Al, Fe, Ga, and In

The layered double hydroxides (LDHs) of Co with trivalent cations decompose irreversibly to yield oxides with the spinel structure. Spinel formation is aided by the oxidation of Co(II) to Co(III) in the ambient atmosphere. When the decomposition is carried out under N-2, the oxidation of Co(II) is suppressed, and the resulting oxide has the rock salt structure. Thus, the Co-Al-CO32-/Cl- LDHs yield oxides of the type Co1- Al-x(2x/3)rectangle O-x/3, which are highly metastable, given the large defect concentration. This defect oxide rapidly reverts back to the original hydroxide on soaking in a Na2CO3 solution. Interlayer NO3- anions, on the other hand, decompose generating a highly oxidizing atmosphere, whereby the Co-Al-NO3- LDH decomposes to form the spinel phase even in a N-2 atmosphere. The oxide with the defect rock salt structure formed by the thermal decomposition of the Co-Fe-CO32- LDH under N2, on soaking in a Na2CO3 solution, follows a different kinetic pathway and undergoes a solution transformation into the inverse spinel Co(Co, Fe)(2)O-4. Fe3+ has a low octahedral crystal field stabilization energy and therefore prefers the tetrahedral coordination offered by the structure of the inverse spinel rather than the octahedral coordination of the parent LDH. Similar considerations do not hold in the case of Ga- and In-containing LDHs, given the considerable barriers to the diffusion of M3+ (M=Ga, In) from octahedral to tetrahedral sites owing to their large size. Consequently, the In-containing oxide residue reverts back to the parent hydroxide, whereas this reconstruction is partial in the case of the Ga-containing oxide. These studies show that the reversible thermal behavior offers a competing kinetic pathway to spinel formation. Suppression of the latter induces the reversible behavior in an LDH that otherwise decomposes irreversibly to the spinel.

Active vibration suppression of beams with discrete actuators using optimal dynamic inversion

Most of the structural elements like beams, cables etc. are flexible and should be modeled as distributed parameter systems (DPS) to represent the reality better. For large structures, the usual approach of 'modal representation' is not an accurate representation. Moreover, for excessive vibrations (possibly due to strong wind, earthquake etc.), external power source (controller) is needed to suppress it, as the natural damping of these structures is usually small. In this paper, we propose to use a recently developed optinial dynamic inversion technique to design a set of discrete controllers for this purpose. We assume that the control force to the structure is applied through finite number of actuators, which are located at predefined locations in the spatial domain. The method used in this paper determines control forces directly from the partial differential equation (PDE) model of the system. The formulation has better practical significance, both because it leads to a closed form solution of the controller (hence avoids computational issues) as well as because a set of discrete actuators along the spatial domain can be implemented with relative ease (as compared to a continuous actuator).

Suppression of charge order, disappearance of antiferromagnetism, and emergence of ferromagnetism in Nd0.5Ca0.5MnO3 nanoparticles

Nd0.5Ca0.5MnO3 nanoparticles (average diameter similar to 20 and 40 nm) are synthesized by the polymeric precursor sol-gel method and characterized by various physico-chemical techniques. Quite strikingly, in the 20 nm particles, the charge-ordered (CO) and the antiferromagnetic phases observed in the bulk below 250 K and 160 K, respectively, are completely absent. Instead, a ferromagnetic (FM) transition is observed at 95 K followed by an insulator-to-metal transition at 75 K. The 40 nm particles show a residual CO phase but a transition to the FM state also occurs, at a slightly higher temperature of 110 K.

Origin of nonmetallicity in PrBa2Cu3O7 from a study of Gd1−xPrxBa2Cu3O7 using soft x-ray absorption at the oxygen K-edge

We present the x-ray absorption data at the oxygen K-edge using total yield technique for Gd1−xPrxba2Cu3O7 (x= 0.0, 0.2, 0.4, 0.6, 0.8, and 1.0). The data clearly to oxygen that the holes doped in the GdBa2Cu3O7 due to oxygen composition are not removed by Pr doping even for the x = 1.0 sample, suggesting that Pr is predominantly in the formally trivalent state. However, the data also clearly indicate the evidence of hybridization effects between the Pr3+ and the adjacent CuO2 layers. This is suggested to be responsible for the progressive suppression of Tc and the metallicity with Pr doping in these systems.

Chronic suppression of testicular function by constant infusion of gonadotropin-releasing hormone agonist and testosterone supplementation in the bonnet monkey (Macaca radiata)

Objective: To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata). Animals: Proven fertile male monkeys exhibiting normal testicular function. Protocol: Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50-mu-g buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored. Results: (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility. Conclusion: Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.

Two-Fermi liquid model for high Tc superconductivity involving suppression of tunnelling by decoherence

We consider a model system of two interacting Fermi-liquids, one of which is light and the other much heavier. In the normal state the lighter component provides a quantum mechanical bath coupled 'ohmically' to the heavier component in the sense of Caldeira and Leggett, suppressing thereby the band (tunnelling) matrix elements of the heavier component. Thus we lose the energy of delocalization. On the other hand, a superconducting ordering stiffens the bath spectral function at low energies and so restores the tunnelling. The resulting regain of the delocalization energy bootstraps so as to stabilize the superconducting order that caused it. It is conceivable that the motions parallel to the easy ab-plane and along the hard c-axis may also effectively correspond to the light and the heavy Fermi-liquids, respectively.

Hybridization of carbon-glass epoxy composites: An approach to achieve low coefficient of thermal expansion at cryogenic temperatures

The paper is based on a study to develop carbon-glass epoxy hybrid composites with desirable thermal properties for applications at cryogenic temperatures. It analyzes the coefficient of thermal expansion of carbon-epoxy and glass-epoxy composite materials and compares it with the properties of carbon-glass epoxy hybrid composites in the temperature range 300 K to 125K. Urethane modified epoxy matrix system is used to make the composite specimens suitable for use even for temperatures as low as 20K. It is noted that the lay-up with 80% of carbon fibers in the total volume fraction of fibers oriented at 30 degrees and 20% of glass fibers oriented at 0 degrees yields near to zero coefficient of thermal expansion as the temperature is lowered from ambient to 125 K. (c) 2010 Elsevier Ltd. All rights reserved.

Active vibration suppression of beams with discrete actuators using optimal dynamic inversion

Most of the structural elements like beams, cables etc. are flexible and should be modeled as distributed parameter systems (DPS) to represent the reality better. For large structures, the usual approach of 'modal representation' is not an accurate representation. Moreover, for excessive vibrations (possibly due to strong wind, earthquake etc.), external power source (controller) is needed to suppress it, as the natural damping of these structures is usually small. In this paper, we propose to use a recently developed optimal dynamic inversion technique to design a set of discrete controllers for this purpose. We assume that the control force to the structure is applied through finite number of actuators, which are located at predefined locations in the spatial domain. The method used in this paper determines control forces directly from the partial differential equation (PDE) model of the system. The formulation has better practical significance, both because it leads to a closed form solution of the controller (hence avoids computational issues) as well as because a set of discrete actuators along the spatial domain can be implemented with relative ease (as compared to a continuous actuator)