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Abstract. Every uniformly exhaustive submeasure is equivalent to a measure. From this, we deduce that every vector measure with compact range in an F-space has a control measure. We also show that c0 (or any E^-space) is a Xspace, i.e. cannot be realized as the quotient of a nonlocally convex f-space by a one-dimensional subspace.

We define and develop an interior partial regularity theory for intrinsic energy minimising fractional harmonic maps from Euclidean space into smooth compact Riemannian manifolds for fractional powers strictly between zero and one. Intrinsic fractional harmonic maps are critical points of an energy whose first variation is a Dirichlet to Neumann map for the harmonic map problem on a half-space with a Riemannian metric which can degenerate/become singular along the boundary, depending on the fractional power. Similarly to the approach used to prove regularity for stationary intrinsic semi-harmonic maps, we take advantage of the connection between fractional harmonic maps and free boundary problems for harmonic maps in order to develop a partial regularity theory for the fractional harmonic maps we consider. In particular, we prove partial regularity for locally minimising harmonic maps with (partially) free boundary data on half-spaces with the aforementioned metrics up to the boundary; fractional harmonic maps then inherit this regularity. As a by-product of our methods we shed some new light on the monotonicity of the average energy of solutions of the degenerate linear elliptic equation related to fractional harmonic functions. Mathematics Subject ClassificationCommunicated by M. Struwe. James Roberts was supported by an Engineering and Physical Sciences Research Council DTA Studentship for much of this research. B James Roberts

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The mechanisms of neuronal differentiation in PC12 cells are still not completely understood. Here, we report that the tumor suppressor PTEN has a profound effect on differentiation by affecting several pathways involved in nerve growth factor (NGF) signaling. When overexpressed in PC12 cells, PTEN (phosphatase and tensin homologue deleted on chromosome ten) blocked neurite outgrowth induced by NGF. In addition, these cells failed to demonstrate the transient mitogenic response to NGF, as well as subsequent growth arrest. Consistent with these observations was a finding that PTEN significantly inhibits NGF-mediated activation of the members of mitogen-activated protein kinase kinase (MEK)͞ mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)͞AKT signaling pathways, crucial for these processes. While exploring possible mechanisms of PTEN effects on NGF signaling, we discovered a significant down-regulation of both high-affinity (TrkA) and low-affinity (p75) NGF receptors in PTEN-overexpressing clones. Subsequent microarray analysis of several independent clonal isolates revealed a myriad of neuronal genes to be affected by PTEN. All of these changes were validated by quantitative PCR. Of particular interest were the genes for the key enzymes of the dopamine synthesis pathway, receptors for different neurotransmitters, and neuron-specific cytoskeleton proteins, among others. Some, but not all effects could be reproduced by pharmacological inhibitors of PI3K and͞or MAPK, suggesting that PTEN may influence some genes by mechanisms independent of these signaling pathways. Our findings may shed new light on the role of this tumor suppressor during normal brain development and suggest a previously uncharacterized mechanism of PTEN action in neuron-like cells.

Modern treatments for cancers of the reproductive age are yielding ever-higher cure rates, but more often than not, the price paid for survival is the loss of reproductive function from gonadal toxicity. Alkylating agents and ionizing radiation have well-recognized deleterious effects within the testes and ovary and cause sterility in a high proportion of patients exposed to these treatments. Preservation of fertility for men simply involves the banking of sperm before treatment, but for women, the storage of gametes is technically very complex and has limited success. Even when faced with the diagnosis of cancer, many reproductive-aged women are burdened by the possibility of never conceiving a child with their own eggs. Fertility preservation for the reproductive-age women with cancer is emerging as a challenging, but rewarding, application of assisted reproductive technologies such as in vitro fertilization. With recent advances in cryopreservation techniques, oocytes, embryos, and ovarian tissue can be banked from these patients before exposure to sterilizing chemotherapy and radiotherapy, providing future fertility options without compromising survival.

A novel pathway of adeno-associated virus (AAV) replication marked by the assembly of circular monomer duplex intermediates (cAAV) has been recently discovered. In the present report we identify a single AD domain of the inverted terminal repeat as a minimal origin of cAAV replication. A small internal palindrome (BB), necessary for optimal Rep-inverted terminal repeat interaction, does not contribute to the efficiency of cAAV replication, while the terminal resolution site is an essential cis-acting element. Furthermore, recombinant cAAV vectors that encompass only the AD domain replicate exclusively in a circular form and no detectable linear duplex replicative intermediates are generated, suggesting that both pathways of AAV replication are independent and can be separated. In addition, we show that cAAVs are efficient templates for encapsidation of single-stranded DNA genomes, an observation that assigns a biological role for these novel replication species. Together, these findings shed new light on the current model of AAV replication and packaging.Adeno-associated virus type 2 (AAV) is a parvovirus nonpathogenic to humans with a genome of approximately 4.7 kb (39). The AAV genome consists of two open reading frames that encode regulatory (Rep) and structural capsid (Cap) proteins flanked by 145-bp inverted terminal repeats (ITR) (39). These ITRs are the only cis-acting elements necessary for virus replication and encapsidation. Recombinant AAVs (rAAV) that do not contain any endogenous coding regions efficiently propagate when Rep and Cap are provided in trans (2, 3). In nature, a secondary infection with helper virus, e.g., adenovirus, is necessary to trigger a productive infection. AAV genomes then undergo replication followed by assembly of infectious virions containing single-stranded DNA (ssDNA) of either positive or negative polarity (2, 4). Adenovirus genes implicated in AAV replication have been identified and include E1A, E1B, E4orf6, E2A, and VA RNA (7,20,21,31,32). Similar to provirus in latently infected cells, AAV genomes can be efficiently rescued from a recombinant cis plasmid following transient transfection into human cells (33-35). The necessary helper functions can be delivered either by adenovirus infection or by transfecting a plasmid encoding a minimal set of adenovirus helper genes (10, 16).Events of AAV lytic infection are described by a commonly accepted self-priming strand displacement model (1). The first 125 nucleotides of AAV termini include elements capable of forming a T-shaped duplex structure (AЈ-BЈ-B-CЈ-C-A) and are followed by a unique 20-bp D-sequence (3, 45). The Rep gene encodes four proteins that are synthesized from the same open reading frame via the use of alternate promoters and splicing (2, 39). Two of these proteins (Rep78 and Rep68) possess site-specific and strand-specific endonuclease activity.They bind to the Rep-binding site (Rbs) mapped to the tetrameric GAGC repeat of the A stem of the ITR and cleave it at the terminal resolution site (trs), positioned b...

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