527 research outputs found
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
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