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

On duality symmetries of supergravity invariants

The role of duality symmetries in the construction of counterterms for maximal supergravity theories is discussed in a field-theoretic context from different points of view. These are: dimensional reduction, the question of whether appropriate superspace measures exist and information about non-linear invariants that can be gleaned from linearised ones. The former allows us to prove that F-term counterterms cannot be E7(7)-invariant in D=4, N=8 supergravity or E6(6)-invariant in D=5 maximal supergravity. This is confirmed by the two other methods which can also be applied to D=4 theories with fewer supersymmetries and allow us to prove that N=6 supergravity is finite at three and four loops and that N=5 supergravity is three-loop finite.Comment: Clarification of arguments and their consistency with higher dimensional divergences added, e.g. we prove the 5D 4L non-renormalisation theorem. The 4L N=6 divergence is also ruled out. References adde

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 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

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 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

Generalised geometry, eleven dimensions and E11

We construct the non-linear realisation of E11 and its first fundamental representation in eleven dimensions at low levels. The fields depend on the usual coordinates of space-time as well as two form and five form coordinates. We derive the terms in the dynamics that contain the three form and six form fields and show that when we restricted their field dependence to be only on the usual space-time we recover the correct self-duality relation. Should this result generalise to the gravity fields then the non-linear realisation is an extension of the maximal supergravity theory, as previously conjectured. We also comment on the connections between the different approaches to generalised geometry.Comment: 17 pages, Trivial typos corrected in version one and a substantial note added which gives the equation of motion relating the gravity field to its dua

Enhancing the African bioethics initiative

BACKGROUND: Medical ethics has existed since the time of Hippocrates. However, formal training in bioethics did not become established until a few decades ago. Bioethics has gained a strong foothold in health sciences in the developed world, especially in Europe and North America. The situation is quite different in many developing countries. In most African countries, bioethics – as established and practiced today in the west- is either non-existent or is rudimentary. DISCUSSION: Though bioethics has come of age in the developed and some developing countries, it is still largely "foreign" to most African countries. In some parts of Africa, some bioethics conferences have been held in the past decade to create research ethics awareness and ensure conformity to international guidelines for research with human participants. This idea has arisen in recognition of the genuine need to develop capacity for reviewing the ethics of research in Africa. It is also a condition required by external sponsors of collaborative research in Africa. The awareness and interest that these conferences have aroused need to be further strengthened and extended beyond research ethics to clinical practice. By and large, bioethics education in schools that train doctors and other health care providers is the hook that anchors both research ethics and clinical ethics. SUMMARY: This communication reviews the current situation of bioethics in Africa as it applies to research ethics workshops and proposes that in spite of the present efforts to integrate ethics into biomedical research in Africa, much still needs to be done to accomplish this. A more comprehensive approach to bioethics with an all-inclusive benefit is to incorporate formal ethics education into health training institutions in Africa