217 research outputs found
Dose-adapted post-transplant cyclophosphamide for HLA-haploidentical transplantation in Fanconi anemia.
We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion (TCD) using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) for Fanconi anemia (FA). With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple pre-transplant comorbidities died, one from sepsis and one from sepsis with associated chronic GVHD. Four patients without preexisting comorbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status. We conclude that adjusted-dosing post-transplant CY is effective in in vivo TCD to promote full donor engraftment in patients with FA
Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.
One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA
Relating Quantum Information to Charged Black Holes
Quantum non-cloning theorem and a thought experiment are discussed for
charged black holes whose global structure exhibits an event and a Cauchy
horizon. We take Reissner-Norstr\"{o}m black holes and two-dimensional dilaton
black holes as concrete examples. The results show that the quantum non-cloning
theorem and the black hole complementarity are far from consistent inside the
inner horizon. The relevance of this work to non-local measurements is briefly
discussed.Comment: 14 pages, 2 figure
Hawking Radiation from Feynman Diagrams
The aim of this letter is to clarify the relationships between Hawking
radiation and the scattering of light by matter falling into a black hole. To
this end we analyze the S-matrix elements of a model composed of a massive
infalling particle (described by a quantized field) and the radiation field.
These fields are coupled by current-current interactions and propagate in the
Schwarzschild geometry. As long as the photons energy is much smaller than the
mass of the infalling particle, one recovers Hawking radiation since our
S-matrix elements identically reproduce the Bogoliubov coefficients obtained by
treating the trajectory of the infalling particle classically. But after a
brief period, the energy of the `partners' of Hawking photons reaches this mass
and the production of thermal photons through these interactions stops. The
implications of this result are discussed.Comment: 12 pages, revtex, no figure
A Cure for HIV Infection: "Not in My Lifetime" or "Just Around the Corner"?
With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding "a cure." The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust. In this "salon" two editors of Pathogens and Immunity, Michael Lederman and Daniel Douek ask whether curing HIV is a realistic, scalable objective. We start with an overview perspective and have asked a number of prominent HIV researchers to add to the discussion
REDD+ on the rocks? Conflict over forest and politics of justice in Vietnam
In Vietnam, villagers involved in a REDD+ (reduced emissions from deforestation and forest degradation) pilot protect areas with rocks which have barely a tree on them. The apparent paradox indicates how actual practices differ from general ideas about REDD+ due to ongoing conflict over forest, and how contestations over the meaning of justice are a core element in negotiations over REDD+. We explore these politics of justice by examining how the actors involved in the REDD+ pilot negotiate the particular subjects, dimensions, and authority of justice considered relevant, and show how politics of justice are implicit to practical decisions in project implementation. Contestations over the meaning of justice are an important element in the practices and processes constituting REDD+ at global, national and local levels, challenging uniform definitions of forest justice and how forests ought to be managed
Holomorphic Quantization on the Torus and Finite Quantum Mechanics
We construct explicitly the quantization of classical linear maps of on toroidal phase space, of arbitrary modulus, using the holomorphic
(chiral) version of the metaplectic representation. We show that Finite Quantum
Mechanics (FQM) on tori of arbitrary integer discretization, is a consistent
restriction of the holomorphic quantization of to the subgroup
, being the principal congruent subgroup mod l,
on a finite dimensional Hilbert space. The generators of the ``rotation group''
mod l, , for arbitrary values of l are determined as
well as their quantum mechanical eigenvalues and eigenstates.Comment: 12 pages LaTeX (needs amssymb.sty). Version as will appear in J.
Phys.
Effective Potential and Spontaneous Symmetry Breaking in the Noncommutative phi^6 Model
We study the conditions for spontaneous symmetry breaking of the
(2+1)-dimensional noncommutative phi^6 model in the small-theta limit. In this
regime, considering the model as a cutoff theory, it is reasonable to assume
translational invariance as a property of the vacuum state and study the
conditions for spontaneous symmetry breaking by an effective potential
analysis. An investigation of up to the two loop level reveals that
noncommutative effects can modify drastically the shape of the effective
potential. Under reasonable conditions, the nonplanar sector of the theory can
become dominant and induce symmetry breaking for values of the mass and
coupling constants not reached by the commutative counterpart.Comment: 11 pages, 2 figures, corrected to match with the PRD versio
PP-wave String Interactions from String Bit Model
We construct the string states ,
and in the Hilbert space of the quantum
mechanical orbifold model so as to calculate the three point functions and the
matrix elements of the light-cone Hamiltonian from the interacting string bit
model. With these string states we show that the three point functions and the
matrix elements of the Hamiltonian derived from the interacting string bit
model up to order precisely match with those computed from the
perturbative SYM theory in BMN limit.Comment: 20 pages, no figure, LaTeX, some changes made and references adde
Background geometry of DLCQ M theory on a p-torus and holography
Via supergravity, we argue that the infinite Lorentz boost along the M theory
circle a la Seiberg toward the DLCQ M theory compactified on a p-torus (p<5)
implies the holographic description of the microscopic theory. This argument
lets us identify the background geometries of DLCQ theory on a p-torus; for
p=0 (p=1), the background geometry turns out to be eleven-dimensional
(ten-dimensional) flat Minkowski space-time, respectively. Holography for these
cases results from the localization of the light-cone momentum. For p = 2,3,4,
the background geometries are the tensor products of an Anti de Sitter space
and a sphere, which, according to the AdS/CFT correspondence, have the
holographic conformal field theory description. These holographic descriptions
are compatible to the microscopic theory of Seiberg based on theory
on a spatial circle with the rescaled Planck length, giving an understanding of
the validity of the AdS/CFT correspondence.Comment: 16 pages, Revtex, no figure
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