Biomedical subjects

Michael Hsieh

Publications and source records attributed to Michael Hsieh.

4 recordsLinked to original sources

PubMed2006

Quantum optimal control: Hessian analysis of the control landscape.

Seeking an effective quantum control entails searching over a landscape defined as the objective as a functional of the control field. This paper considers the problem of driving a state-to-state transition in a finite level quantum system, and analyzes the local topology of the landscape of the final transition probability in terms of the variables specifying the control field. Numerical calculation of the eigenvalues of the Hessian of the transition probability with respect to the control field variables reveals systematic structure in the spectra reflecting the existence of a generic and simple control landscape topology. An illustration shows that the number of nonzero Hessian eigenvalues is determined by the number of quantum states in the system. The Hessian eigenvectors associated with its nonzero eigenvalues are shown to give insight into the cooperative roles of the control variables. The practical consequences of these findings for quantum control are discussed.

Journal Article↗

PubMed2006

Optimal control landscapes for quantum observables.

The optimal control of quantum systems provides the means to achieve the best outcome from redirecting dynamical behavior. Quantum systems for optimal control are characterized by an evolving density matrix and a Hermitian operator associated with the observable of interest. The optimal control landscape is the observable as a functional of the control field. The features of interest over this control landscape consist of the extremum values and their topological character. For controllable finite dimensional quantum systems with no constraints placed on the controls, it is shown that there is only a finite number of distinct values for the extrema, dependent on the spectral degeneracy of the initial and target density matrices. The consequences of these findings for the practical discovery of effective quantum controls in the laboratory is discussed.

Journal Article↗

PubMed2004

Complete allogeneic hematopoietic chimerism achieved by in utero hematopoietic cell transplantation and cotransplantation of LLME-treated, MHC-sensitized donor lymphocytes.

OBJECTIVE: In utero hematopoietic cell transplantation (IUHCT) typically achieves low-level mixed hematopoietic chimerism. However, the goal of IUHCT is to achieve therapeutic levels of chimerism. We hypothesized that prenatal adoptive immunotherapy might achieve high-level donor chimerism after IUHCT. MATERIALS AND METHODS: BALB/CE15 fetal mice were transplanted with a mixture of C57BL/6 (B6) T-cell-depleted bone marrow (TCD BM) cells and splenocytes from B6 mice presensitized to BALB/C alloantigen. The splenocytes were preincubated in L-leucyl-L-leucine methyl ester (LLME), to minimize graft vs host disease (GVHD). Recipients were followed after birth for donor cell chimerism and GVHD. RESULTS: Full donor hematopoietic chimerism following a single prenatal transplant was achieved in seven transplanted animals. Fully chimeric animals were healthy, without evidence of GVHD, and maintained their engraftment for the duration of the study (48 weeks). However, the addition of presensitized LLME-treated cells decreased survival until weaning relative to TCD BM alone, suggesting that some animals were lost to acute GVHD. Surviving chimeric animals demonstrated increased frequencies of T-regulatory cell populations in their spleen and BM, suggesting that they had successfully suppressed GVHD, allowing survival. CONCLUSIONS: This study represents "proof in principle" that prenatal immunotherapeutic strategies may achieve complete hematopoietic engraftment across full MHC barriers when combined with IUHCT. However, strategies with greater hematopoietic specificity must be developed prior to consideration of clinical application.

Animals↗

PubMed2002

High-level allogeneic chimerism achieved by prenatal tolerance induction and postnatal nonmyeloablative bone marrow transplantation.

Clinical application of allogeneic bone marrow transplantation (BMT) has been limited by toxicity related to cytoreductive conditioning and immune response. In utero hematopoietic stem cell transplantation (IUHSCT) is a nonablative approach that achieves mixed chimerism and donor-specific tolerance but has been limited by minimal engraftment. We hypothesized that mixed chimerism achieved by IUHSCT could be enhanced after birth by nonmyeloablative total body irradiation (TBI) followed by same-donor BMT. To test this hypothesis, mixed chimerism was created by IUHSCT in a major histocompatibility complex-mismatched strain combination. After birth, chimeric animals received nonmyeloablative TBI followed by transplantation of donor congenic bone marrow cells. Our results show that: (1) low-level chimerism after IUHSCT can be enhanced to high-level chimerism by this strategy; (2) enhancement of chimerism is dependent on dose of TBI; (3) the mechanism of TBI enhancement is via a transient competitive advantage for nonirradiated hematopoietic stem cells; (4) engraftment observed in the tolerant, fully allogeneic IUHSC transplant recipient is equivalent to a congenic recipient; and (5) host-reactive donor lymphocytes are deleted with no evidence of graft-versus-host disease. This study supports the concept of prenatal tolerance induction to facilitate nonmyeloablative postnatal strategies for cellular therapy. If clinically applicable, such an approach could dramatically expand the application of IUHSCT.

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