Perinatal Gene Transfer to the Liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer

Ten-Dimensional Super-Twistors and Super-Yang-Mills

Four-dimensional super-twistors provide a compact covariant description of on-shell N=4 d=4 super-Yang-Mills. In this paper, ten-dimensional super-twistors are introduced which similarly provide a compact covariant description of on-shell d=10 super-Yang-Mills. The super-twistor variables are Z=(lambda^alpha, mu_alpha, Gamma^m) where lambda^alpha and mu_alpha are constrained bosonic d=10 spinors and Gamma^m is a constrained fermionic d=10 vector. The Penrose map relates the twistor superfield Phi(Z) with the d=10 super-Yang-Mills vertex operator lambda^alpha A_alpha(x,theta) which appears in the pure spinor formalism of the superstring, and the cubic super-Yang-Mills amplitude is proportional to the super-twistor integral \int dZ Phi_1 Phi_2 Phi_3.Comment: 14 pages harvmac, added short clarificatio

Entropy of the self-dual string soliton

We compute the entropy and the corresponding central charge of the self-dual string soliton in the supergravity regime using the blackfold description of the fully localized M2-M5 intersection.Comment: 15 pages, 1 figure, harvma

The Overall Coefficient of the Two-loop Superstring Amplitude Using Pure Spinors

Using the results recently obtained for computing integrals over (non-minimal) pure spinor superspace, we compute the coefficient of the massless two-loop four-point amplitude from first principles. Contrasting with the mathematical difficulties in the RNS formalism where unknown normalizations of chiral determinant formulae force the two-loop coefficient to be determined only indirectly through factorization, the computation in the pure spinor formalism can be smoothly carried out.Comment: 29 pages, harvmac TeX. v2: add reference

Off-shell supergravity-matter couplings in three dimensions

We develop the superspace geometry of N-extended conformal supergravity in three space-time dimensions. General off-shell supergravity-matter couplings are constructed in the cases N=1,2,3,4.Comment: 73 pages; V5: typos in eqs. (3.4b), (3.17) and (4.24) correcte

The Omega Deformation From String and M-Theory

We present a string theory construction of Omega-deformed four-dimensional gauge theories with generic values of \epsilon_1 and \epsilon_2. Our solution gives an explicit description of the geometry in the core of Nekrasov and Witten's realization of the instanton partition function, far from the asymptotic region of their background. This construction lifts naturally to M-theory and corresponds to an M5-brane wrapped on a Riemann surface with a selfdual flux. Via a 9-11 flip, we finally reinterpret the Omega deformation in terms of non-commutative geometry. Our solution generates all modified couplings of the \Omega-deformed gauge theory, and also yields a geometric origin for the quantum spectral curve of the associated quantum integrable system.Comment: LaTeX, 35 pages, 1 figure. Appendix on couplings of hypermultiplets in N=4 SYM adde

R^4 counterterm and E7(7) symmetry in maximal supergravity

The coefficient of a potential R^4 counterterm in N=8 supergravity has been shown previously to vanish in an explicit three-loop calculation. The R^4 term respects N=8 supersymmetry; hence this result poses the question of whether another symmetry could be responsible for the cancellation of the three-loop divergence. In this article we investigate possible restrictions from the coset symmetry E7(7)/SU(8), exploring the limits as a single scalar becomes soft, as well as a double-soft scalar limit relation derived recently by Arkani-Hamed et al. We implement these relations for the matrix elements of the R^4 term that occurs in the low-energy expansion of closed-string tree-level amplitudes. We find that the matrix elements of R^4 that we investigated all obey the double-soft scalar limit relation, including certain non-maximally-helicity-violating six-point amplitudes. However, the single-soft limit does not vanish for this latter set of amplitudes, which suggests that the E7(7) symmetry is broken by the R^4 term.Comment: 33 pages, typos corrected, published versio

Non-abelian Action for Multiple Five-Branes with Self-Dual Tensors

We construct an action for non-abelian 2-form in 6-dimensions. Our action consists of a non-abelian generalization of the abelian action of Perry and Schwarz for a single five-brane. It admits a self-duality equation on the field strength as the equation of motion. It has a modified 6d Lorentz symmetry. On dimensional reduction on a circle, our action gives the standard 5d Yang-Mills action plus higher order corrections. Based on these properties, we propose that our theory describes the gauge sector of multiple M5-branes in flat space.Comment: LaTeX, 26 pages. v2: improved discussion of Lorentz symmetry. ref added. v3: add comments in the discussion section on the inclusion of scalar fields and supersymmetry; title changed to a more suitable one; version published in JHE

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Revisiting the S-matrix approach to the open superstring low energy effective lagrangian

The conventional S-matrix approach to the (tree level) open string low energy effective lagrangian assumes that, in order to obtain all its bosonic ${\alpha'}^N$ order terms, it is necessary to know the open string (tree level) $(N+2)$-point amplitude of massless bosons, at least expanded at that order in $\alpha'$. In this work we clarify that the previous claim is indeed valid for the bosonic open string, but for the supersymmetric one the situation is much more better than that: there are constraints in the kinematical bosonic terms of the amplitude (probably due to Spacetime Supersymmetry) such that a much lower open superstring $n$-point amplitude is needed to find all the ${\alpha'}^N$ order terms. In this `revisited' S-matrix approach we have checked that, at least up to ${\alpha'}^4$ order, using these kinematical constraints and only the known open superstring 4-point amplitude, it is possible to determine all the bosonic terms of the low energy effective lagrangian. The sort of results that we obtain seem to agree completely with the ones achieved by the method of BPS configurations, proposed about ten years ago. By means of the KLT relations, our results can be mapped to the NS-NS sector of the low energy effective lagrangian of the type II string theories implying that there one can also find kinematical constraints in the $N$-point amplitudes and that important informations can be inferred, at least up to ${\alpha'}^4$ order, by only using the (tree level) 4-point amplitude.Comment: 34 pages, 3 figure, Submitted on Aug 4, 2012, Published on Oct 15, 201