Mechanoregulation and mechanotransduction in skeletal tissue differentiation

Thesis (Ph.D.)--Boston UniversityMechanical factors play a critical role in the development, maintenance and repair of skeletal tissues. Mechanical stimulation can alter the course of healing by directing the differentiation of mesenchymal progenitor cells into the cells that form the various skeletal tissues, and can enhance or impair the repair of orthopaedic injuries. Several mechanoregulatory hypotheses describing the relationships between mechanical stimuli and skeletal tissue differentiation have been proposed; however, these hypotheses have not been fully tested, nor have the underlying mechanisms been established. Identification of the specific mechanical stimuli and molecular mechanisms that direct the differentiation of mesenchymal progenitor cells would provide insight for treating injuries. The focus of this dissertation was to further our understanding of the mechanobiology of skeletal tissue differentiation by identifying the mechanisms that regulate the differentiation of mesenchymal progenitor cells. The first part of this dissertation identified consistent associations between the patterns of the formation of skeletal tissues (bone, cartilage, fibrocartilage and fibrous tissues) and the magnitudes of strains (shear and principal strains) in a mechanically-stimulated bone defect in vivo. The second part of this dissertation found evidence that the Rho-family GTPases, as well as adhesion receptors and their associated focal adhesion proteins, may be possible mediators of the mechanotransduction mechanisms involved in the decisions of cell fate of the mesenchymal progenitor cells within the stimulated tissues. Finally, in an anticipation of the next steps in research on mechano-regulation of tissue differentiation, a microindentation technique was developed to determine the poroelastic material properties of the soft tissues forming in the callus. The values of Young's modulus, Poisson's ratio and permeability of articular cartilage were measured at the microscale and compared to those determined using standard macroscale techniques. Together, the findings of this dissertation further our understanding of the mechanoregulation of skeletal tissue differentiation, and can be used to inform and improve the various hypotheses regarding the mechanoregulation of tissue differentiation. Clinically, these results could potentially direct the development of therapies to improve treatment outcomes and reduce recovery time

Using Spin Correlations to Distinguish Zh from ZA at the International Linear Collider

We investigate how to exploit the spin information imparted to the Z boson in associated Higgs production at a future linear collider as an aid in distinguishing between CP-even and CP-odd Higgs bosons. We apply a generalized spin-basis analysis which allowsus to study the possibilities offered by non-traditional choices of spin projection axis. In particular, we find that the Z bosons produced in association with a CP-even Higgs via polarized collisions are in a single transverse spin-state (>90% purity) when we use the Zh-transverse basis, provided that the Z~bosons are not ultra-relativistic (speed <0.9c). This same basis applied to the associated production of a CP-odd Higgs yields Z's that are an approximately equal mixture of longitudinal and transverse polarizations. We present a decay angular distribution which could be used to distinguish between the CP-even and CP-odd cases. Finally, we make a few brief remarks about how this distribution would be affected if the Higgs boson turns out to not be a CP-eigenstate.Comment: 48 pages, 18 figures, revtex

A Two-Coordinate Nickel Imido Complex That Effects C−H Amination

An exceptionally low coordinate nickel imido complex, (IPr*)Ni═N(dmp) (2) (dmp = 2,6-dimesitylphenyl), has been prepared by the elimination of N_2 from a bulky aryl azide in its reaction with (IPr*)Ni(η^6-C_7H_8) (1). The solid-state structure of 2 features two-coordinate nickel with a linear C−Ni−N core and a short Ni−N distance, both indicative of multiple-bond character. Computational studies using density functional theory showed a Ni═N bond dominated by Ni(dπ)−N(pπ) interactions, resulting in two nearly degenerate singly occupied molecular orbitals (SOMOs) that are Ni−N π* in character. Reaction of 2 with CO resulted in nitrene-group transfer to form (dmp)NCO and (IPr*)Ni(CO)_3 (3). Net C−H insertion was observed in the reaction of 2 with ethene, forming the vinylamine (dmp)NH(CH═CH_2) (5) via an azanickelacyclobutane intermediate, (IPr*)Ni{N,C:κ^2-N(dmp)CH_2CH_2} (4)

Synthesis and Characterization of Three-Coordinate Ni(III)-Imide Complexes

A new family of low-coordinate nickel imides supported by 1,2-bis(di-tert-butylphosphino)ethane was synthesized. Oxidation of nickel(II) complexes led to the formation of both aryl- and alkyl-substituted nickel(III)-imides, and examples of both types have been isolated and fully characterized. The aryl substituent that proved most useful in stabilizing the Ni(III)-imide moiety was the bulky 2,6-dimesitylphenyl. The two Ni(III)-imide compounds showed different variable-temperature magnetic properties but analogous EPR spectra at low temperatures. To account for this discrepancy, a low-spin/high-spin equilibrium was proposed to take place for the alkyl-substituted Ni(III)-imide complex. This proposal was supported by DFT calculations. DFT calculations also indicated that the unpaired electron is mostly localized on the imide nitrogen for the Ni(III) complexes. The results of reactions carried out in the presence of hydrogen donors supported the findings from DFT calculations that the adamantyl substituent was a significantly more reactive hydrogen-atom abstractor. Interestingly, the steric properties of the 2,6-dimesitylphenyl substituent are important not only in protecting the Ni═N core but also in favoring one rotamer of the resulting Ni(III)-imide, by locking the phenyl ring in a perpendicular orientation with respect to the NiPP plane

Fluorescence measurements of the thermal control experiments coatings on LDEF S0069 and A0114

Fluorescence measurements were made on the thermal control coatings from the Long Duration Experiment Facility (LDEF) S0069, Thermal Control Surfaces Experiment (TCSE); and the A0114, Interaction of Atomic Oxygen with Material Surfaces in Low Earth orbit. Fluorescence was observed in two types of thermal control coatings and is attributed to pigments or binders. In addition, fluorescence measurement on the silver Teflon from the front cover of TCSE led to confirmation of damage (cracking) to the metal layers during application

The equation of state of molybdenum at 1400 °C

Shock compression data to 96 GPa for pure molybdenum, initially heated to 1400 °C, are presented. Finite strain analysis of the data gives a bulk modulus at 1400 °C, K_(0S), of 244 ± 2 GPa and its pressure derivative, K′_(0S), of 4. A fit of shock velocity to particle velocity gives the coefficients of U_S = c_0 + sU_P to be c_0 = 4.77 ± 0.06 km/s and s = 1.43 ± 0.05. From the zero‐pressure sound speed c_0, a bulk modulus of 232 ± 6 GPa is calculated which is consistent with extrapolation of ultrasonic elasticity measurements. The temperature derivative of the bulk modulus at zero pressure, ∂K_(0S)/∂T|_P, is approximately −0.012 GPa/K. A thermodynamic model is used to show that the thermodynamic Grüneisen parameter is proportional to the density and independent of temperature. The Mie–Grüneisen equation of state adequately describes the high‐temperature behavior of molybdenum under the present range of shock loading conditions