Identification Of Ets1 As Ase Binding Protein: Unique Role In Age‐Related Gene Regulation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106056/1/jth00156.pd

Mechanisms of homeostasis of blood coagulation factors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106052/1/jth05170.pd

Functional pan‐universality of the age‐related regulatory elements ASE and AIE, and development of age dimension technology

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106078/1/jth05171.pd

Spectral-Function Sum Rules in Supersymmetry Breaking Models

The technique of Weinberg's spectral-function sum rule is a powerful tool for a study of models in which global symmetry is dynamically broken. It enables us to convert information on the short-distance behavior of a theory to relations among physical quantities which appear in the low-energy picture of the theory. We apply such technique to general supersymmetry breaking models to derive new sum rules.Comment: 18 pages, 1 figur

Reduction techniques of the back gate effect in the SOI Pixel Detector

We have fabricated monolithic pixel sensors in 0.2 μm Silicon-On-Insulator (SOI) CMOS technology, consisting of a thick sensor layer and a thin circuit layer with an insulating buried-oxide, which has many advantages. However, it has been found that the applied electric field in the sensor layer also affects the transistor operation in the adjacent circuit layer. This limits the applicable sensor bias well below the full depletion voltage. To overcome this, we performed a TCAD simulation and added an additional p-well (buried pwell) in the SOI process. Designs and preliminary results are presented

Electroweak Corrections and Unitarity in Linear Moose Models

We calculate the form of the corrections to the electroweak interactions in the class of Higgsless models which can be "deconstructed'' to a chain of SU(2) gauge groups adjacent to a chain of U(1) gauge groups, and with the fermions coupled to any single SU(2) group and to any single U(1) group along the chain. The primary advantage of our technique is that the size of corrections to electroweak processes can be directly related to the spectrum of vector bosons ("KK modes"). In Higgsless models, this spectrum is constrained by unitarity. Our methods also allow for arbitrary background 5-D geometry, spatially dependent gauge-couplings, and brane kinetic energy terms. We find that, due to the size of corrections to electroweak processes in any unitary theory, Higgsless models with localized fermions are disfavored by precision electroweak data. Although we stress our results as they apply to continuum Higgsless 5-D models, they apply to any linear moose model including those with only a few extra vector bosons. Our calculations of electroweak corrections also apply directly to the electroweak gauge sector of 5-D theories with a bulk scalar Higgs boson; the constraints arising from unitarity do not apply in this case.Comment: 50 pages, 11 eps figures, typos correcte

Higgsinoless Supersymmetry and Hidden Gravity

We present a simple formulation of non-linear supersymmetry where superfields and partnerless fields can coexist. Using this formalism, we propose a supersymmetric Standard Model without the Higgsino as an effective model for the TeV-scale supersymmetry breaking scenario. We also consider an application of the Hidden Local Symmetry in non-linear supersymmetry, where we can naturally incorporate a spin-two resonance into the theory in a manifestly supersymmetric way. Possible signatures at the LHC experiments are discussed.Comment: 30 pages, 3 figures, references added, version to appear in JHE

Effects of a second intron on recombinant MFG retroviral vector

 The retroviral vectors based on an MFG-type backbone have superior expression characteristics, in part, due to the presence of the retroviral chimeric intron (MFG intron). We tested the hypothesis that inclusion of a second intron in MFG vectors may influence packaging and/or LTR-driven transgene expression. We constructed two MFG retroviral vectors, MFG/hFIXc and MFG/hFIXm2, containing human factor IX (hFIX) cDNA without and with a 0.3-kb hFIX intron, respectively. When tested with primary mouse myoblasts or HepG2 cells in culture for transient expression activity, pMFG/hFIXm2 plasmid produced two-to-three fold higher hFIX than pMFG/hFIXc. These vectors produced equivalent retroviral titers from packaging cells. In transduced cells, the splicing of the MFG intron in the retroviral transcripts occured at a similar efficiency; however, MFG/hFIXc virus gave two-fold higher hFIX expression than that of the MFG/hFIXm2 viral infection. Analyses of MFG/hFIXm2 virion RNA and transduced cell genomic DNA suggested that, although the hFIX intron containing viral RNA are packaged, these viruses fail to integrate their transgenes into the genome of transduced cells, suggesting a block at the reverse transcription and/or integration steps. Similar results were also obtained with the prototype vectors, LIXcSN and LIXm2SN, lacking the MFG intron. Together, these results suggest that a hFIX cDNA sequence in the retroviral vectors performs better over hFIX intron-containing minigene.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42460/1/705-146-3-601_11460601.pd

Bone marrow stromal cells as a genetic platformfor systemic delivery of therapeutic proteins in vivo : human factor IX model

Background Hemophilia B is an X-linked bleeding disorder that results from a deficiency in functional coagulation factor IX (hFIX). In patients lacking FIX, the intrinsic coagulation pathway is disrupted leading to a lifelong, debilitating and sometimes fatal disease. Methods We have developed an ex vivo gene therapy system using genetically modified bone marrow stromal cells (BMSCs) as a platform for sustained delivery of therapeutic proteins into the general circulation. This model exploits the ability of BMSCs to form localized ectopic ossicles when transplanted in vivo . BMSCs were transduced with MFG-hFIX, a retroviral construct directing the expression of hFIX. The biological activity of hFIX expressed by these cells was assessed in vitro and in vivo . Results Transduced cells produced biologically active hFIX in vitro with a specific activity of 90% and expressed hFIX at levels of ∼497 ng/10 6 cells/24 h and 322 ng/10 6 cells/24 h for human and porcine cells, respectively. The secretion of hFIX was confirmed by Western blot analysis of the conditioned medium using a hFIX-specific antibody. Transduced BMSCs (8 × 10 6 cells per animal) were transplanted within scaffolds into subcutaneous sites in immunocompromised mice. At 1 week post-implantation, serum samples contained hFIX at levels greater than 25 ng/ml. Circulating levels of hFIX gradually decreased to 11.5 ng/ml at 1 month post-implantation and declined to a stable level at 6.1 ng/ml at 4 months. Conclusions These findings demonstrate that genetically modified BMSCs can continuously secrete biologically active hFIX from self-contained ectopic ossicles in vivo , and thus represent a novel delivery system for releasing therapeutic proteins into the circulation. Copyright © 2002 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35232/1/292_ftp.pd