Papillomavirus E5: the smallest oncoprotein with many functions

Papillomaviruses (PVs) are established agents of human and animal cancers. They infect cutaneous and mucous epithelia. High Risk (HR) Human PVs (HPVs) are consistently associated with cancer of the uterine cervix, but are also involved in the etiopathogenesis of other cancer types. The early oncoproteins of PVs: E5, E6 and E7 are known to contribute to tumour progression. While the oncogenic activities of E6 and E7 are well characterised, the role of E5 is still rather nebulous. The widespread causal association of PVs with cancer makes their study worthwhile not only in humans but also in animal model systems. The Bovine PV (BPV) system has been the most useful animal model in understanding the oncogenic potential of PVs due to the pivotal role of its E5 oncoprotein in cell transformation. This review will highlight the differences between HPV-16 E5 (16E5) and E5 from other PVs, primarily from BPV. It will discuss the targeting of E5 as a possible therapeutic agent

Formalising Confluence in PVS

Confluence is a critical property of computational systems which is related with determinism and non ambiguity and thus with other relevant computational attributes of functional specifications and rewriting system as termination and completion. Several criteria have been explored that guarantee confluence and their formalisations provide further interesting information. This work discusses topics and presents personal positions and views related with the formalisation of confluence properties in the Prototype Verification System PVS developed at our research group.Comment: In Proceedings DCM 2015, arXiv:1603.0053

The persistent vegetative state: legal and ethical issues

Recent advances in technology and medical expertise have enabled doctors to prolong the lives of many severely injured patients who only a few years ago would have died from their injuries. The prolongation of life by such measures has raised many legal, ethical and social issues. When in 1992 the House of Lords determined in Airdale NHS Trust V Bland that life-supporting measures, including artificial nutrition and hydration (ANH) might lawfully be withdrawn from Anthony Bland, a patient in a persistent vegetative state (PVS), attention was focused on these issues particularly as they apply to the patient in PVS. Since the PVS patient is neither competent to refuse treatment, nor is he dying or suffering, the reasons normally advanced for withdrawing life-supporting measures do not apply. In Bland, their Lordships relied on the best interests test laid down in Re F (mental patient: sterilisation) [1989] 2 All ER 545, and, with the exception of Lord Mustill, on the Bolam test (Bolam v Friern Barnet Hospital Management Committee) [1957] 1 WLR 582. This thesis examines the decision mBland and addresses some of the issues raised. The appropriateness of the best interests test as applied to the patient in PVS is explored and compared with the approach of substituted judgement employed in some other common law jurisdictions. The relevance of the Bolam test to decisions regarding the withdrawal of life-supporting measures is considered. The legal requirements for the withdrawal of ANH are discussed, together with the ethical debate and the moral dilemmas posed by its withdrawal. Finally, the question as to whether the decision in Bland is good law is addressed, and it will be argued that whilst it may be morally acceptable to withdraw ANH from some patients, as regards a patient in PVS, the moral imperative is that we should not

Short- and long-term experience in pulmonary vein segmental ostial ablation for paroxysmal atrial fibrillation*

Introduction: Segmental ostial pulmonary vein isolation (PVI) is considered a potentially curative therapeutic approach in the treatment of paroxysmal atrial fibrillation (PAF). There is only limited data available on the long-term effect of this procedure. Methods: Patients (Pts) underwent a regular clinical follow up visit at 3, 6 and 24 months after PVI. Clinical success was classified as complete (i.e. no arrhythmia recurrences, no antiarrhythmic drug), partial (i.e. no/only few recurrences, on drug) or as a failure (no benefit). The clinical responder rate (CRR) was determined by combining complete and partial success. Results: 117 patients (96 male, 21 female), aged 51±11 years (range 25 to 73) underwent a total of 166 procedures (1.4/patient) in 2-4 pulmonary veins (PV). 115 patients (98%) had AF, 2 patients presented with regular PV atrial tachycardia. ,109/115 patients. exhibited PAF as the primary arrhythmia (versus persistent AF). A total of 113 patients with PVI in the years 2001 to 2003 were evaluated for their CRR after 6 (3) months. A single intervention was carried out in 63 patients (55.8%), two interventions were performed in 45 patients (39.8%) and three interventions in 5 patients (4.4%). The clinical response demonstrated a complete success of 52% (59 patients), a partial success of 26% (29 patients) and a failure rate of 22% (25 patients), leading to a CRR of 78% (88 patients). Ostial PVI in all 4 PVs exhibited a tendency towards higher curative success rates (54% versus 44% in patients with 3 PVs ablated for the 6 month follow up). Long-term clinical outcome was evaluated in 39 patients with an ablation attempt at 3 PVs only (excluding the right inferior PV in our early experience) and a mean clinical follow up of 21±6 months. At this point in time the success rate was 41% (complete, 16 patients) and 21% (partial, 8 patients), respectively, adding up to a CRR of 62% (24 patients). In total, 20 patients (17.1%) had either a single or 2 (3 patients, 2.6%) complications independent of the number of procedures performed with PV stenosis as the leading cause (7.7%). Conclusion: The CRR of patients with medical refractory PAF in our patient cohort is 78% at the 6 month follow up. PV stenosis is the main cause for procedure-related complications. Ablation of all 4 PV exhibits a tendency towards higher complete success rates despite equal CRR. Calculation of the clinical response after a mid- to long-term follow of 21±6 months in those patients with an ostial PVI in only 3 pulmonary veins (sparing the right inferior PV) shows a further reduction to 62%, exclusively caused by a drop in patients with a former partial success. To evaluate the long-term clinical benefit of segmental ostial PVI in comparison with other ablation techniques, more extended follow up periods are mandatory, including a larger study cohort and a detailed description of procedural parameters

Pre-melting of crossing vortex lattices

The pre-melting of high vortex density planes observed recently in layered superconductors in tilted magnetic field is explained theoretically. Based on the structural information of the crossing lattices of pancake and Josephson vortices the effective vortex cage potential at different lattice sites is determined numerically. Melting takes place when the thermal energy allows proliferation of vacancy-interstitial pairs. It is found that the increased density of pancake vortex stacks in the planes containing Josephson vortices, rather than their incommensurate structure, is the main cause for pre-melting.Comment: 5 pages, 4 figure

The London theory of the crossing-vortex lattice in highly anisotropic layered superconductors

A novel description of Josephson vortices (JVs) crossed by the pancake vortices (PVs) is proposed on the basis of the anisotropic London theory. The field distribution of a JV and its energy have been calculated for both dense ($a\lambda_J$) PV lattices with distance $a$ between PVs, and the nonlinear JV core size $\lambda_J$. It is shown that the ``shifted'' PV lattice (PVs displaced mainly along JVs in the crossing vortex lattice structure), formed in high out-of-plane magnetic fields transforms into the PV lattice ``trapped'' by the JV sublattice at a certain field, lower than $\Phi_0/\gamma^2s^2$, where $\Phi_0$ is the flux quantum, $\gamma$ is the anisotropy parameter and $s$ is the distance between CuO$_2$ planes. With further decreasing $B_z$, the free energy of the crossing vortex lattice structure (PV and JV sublattices coexist separately) can exceed the free energy of the tilted lattice (common PV-JV vortex structure) in the case of $\gamma s<\lambda_{ab}$ with the in-plane penetration depth $\lambda_{ab}$ if the low ($B_x<\gamma\Phi_0/\lambda_{ab}^2$) or high ($B_x\gtrsim \Phi_0/\gamma s^2$) in-plane magnetic field is applied. It means that the crossing vortex structure is realized in the intermediate field orientations, while the tilted vortex lattice can exist if the magnetic field is aligned near the $c$-axis and the $ab$-plane as well. In the intermediate in-plane fields $\gamma\Phi_0/\lambda_{ab}^2\lesssim B_x \lesssim \Phi_0/\gamma s^2$, the crossing vortex structure with the ``trapped'' PV sublattice seems to settle in until the lock-in transition occurs since this structure has the lower energy with respect to the tilted vortex structure in the magnetic field ${\vec H}$ oriented near the $ab$-plane.Comment: 15 pages, 6 figures, accepted for publication in PR