Numerical studies of tunneling in a nonharmonic time-dependent potential

Azbel' has recently carried out a WKB-analysis of the effects of a nonharmonic time-dependent perturbation embedded in an opaque potential barrier. He suggests the existence of three different transmission regimes: direct tunneling, activation assisted tunneling, and elevator resonant activation. We address the same problem with a numerical technique, and find qualitative agreement with Azbel's picture.Comment: LaTeX document, 15 pages. 4 figures (Fig. 2 comes in 7 pages) in postscript appended to the LaTeX documen

Death switch for gene therapy: application to erythropoietin transgene expression

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The effectiveness of the caspase-9-based artificial 'death switch' as a safety measure for gene therapy based on the erythropoietin (Epo) hormone was tested in vitro and in vivo using the chemical inducer of dimerization, AP20187. Plasmids encoding the dimeric murine Epo, the tetracycline-controlled transactivator and inducible caspase 9 (ptet-mEpoD, ptet-tTAk and pSH1/Sn-E-Fv'-Fvls-casp9-E, respectively) were used in this study. AP20187 induced apoptosis of iCasp9-modified C2C12 myoblasts. In vivo, two groups of male C57BI/6 mice, 8-12 weeks old, were injected intramuscularly with 5 mu g/50 g ptet-mEpoD and 0.5 mu g/50 g ptet-tTAk. There were 20 animals in group 1 and 36 animals in group 2. Animals from group 2 were also injected with the 6 mu g/50 g iCasp9 plasmid. Seventy percent of the animals showed an increase in hematocrit of more than 65% for more than 15 weeks. AP20187 administration significantly reduced hematocrit and plasma Epo levels in 30% of the animals belonging to group 2. TUNEL-positive cells were detected in the muscle of at least 50% of the animals treated with AP20187. Doxycycline administration was efficient in controlling Epo secretion in both groups. We conclude that inducible caspase 9 did not interfere with gene transfer, gene expression or tetracycline control and may be used as a safety mechanism for gene therapy. However, more studies are necessary to improve the efficacy of this technique, for example, the use of lentivirus vector.437634644Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Protein deficiency balance as a predictor of clinical outcome in hereditary spherocytosis

Vertical and horizontal interactions between membrane constituents account for integrity, strength and deformability of the erythrocyte. Disruption of vertical interactions caused by membrane protein deficiencies in hereditary spherocytosis (HS), favor membrane vesiculation with development of spherocytic cells. Our aim was to evaluate the hematological and clinical presentation of HS according to the type and amount of protein deficiency. We studied 81 Portuguese individuals, 71 belonging to 21 families plus 10 unrelated subjects, and found that 51 of them were HS patients. Patients were classified as presenting mild, typical or severe HS, according to laboratory results and clinical follow-up. We performed screening tests and the standardized electrophoretic membrane protein analysis to identify and quantify protein deficiencies. We found band 3 and ankyrin deficiencies as the major causes for HS. The ratios between the value of the primary and/or secondary protein deficiencies showed significantly different values according to the severity of HS, and a significant inverse correlation with the severity of HS was observed. In mild HS, the ratios between protein deficiencies reflected equivalent protein deficiencies, while an unbalance was observed in typical HS, which was enhanced in severe HS. Our data suggest that the relative quantification of each major membrane protein and of the ratios between the values of protein deficiencies may be helpful in providing additional data about the clinical outcome of HS

The governance and practice of change of sustainable consumption and production." Introduction to the ideas and recommendations presented in the articles in this special issue of the journal of cleaner production.

This special issue is a result of work of Sustainable Consumption Research Exchanges (SCORE!). This EU supported network project under the 6th Framework Program engaged a few hundred professionals interested in sustainable consumption and production (SCP) in Europe and beyond. A key goal of the network is to enhance understanding how radical reductions of environmental impacts and at global level a more equitable growth can be realised. In April 2006, SCORE! organised a workshop in Copenhagen with support of the European Environment Agency, titled 'Governance of change to Sustainable Consumption and Production'. This special issue contains 7 papers based on presentations during that workshop. It further contains a summary of the main conclusions drawn by the SCORE! project team on the basis of a broader review of radical change to SCP from a business, design, consumer and system innovation perspective. The conclusion is unambiguously that governments cannot 'outsource politics', but must form a 'triangle of change' with business and consumers. We have further to understand the systemic nature of the change required. Some policies are currently more viable than others, given existing mega-trends, mega-structures and mega-views, which cannot be changed easily in the short-term and usually cannot be tackled head-on. Such issues, like paradigms on the possibility of continuous exponential growth, the belief in free markets and trade, need a longer-term deliberative process before change is possible

Amputations In Sickle Cell Disease: Case Series And Literature Review

In this study, we describe four new patients with sickle cell disease who had limb amputations. Two of the patients had sickle cell anemia [Hb S (HBB: c.20A>T) (beta(5)/beta(5))] with refractory leg ulcers that required amputations. The third patient had sickle cell trait with an extensive leg ulcer that was associated with epidermoid carcinoma. The fourth patient had amputations of both forearms and feet due to a misdiagnosis of dactylitis. Review of the literature showed that the indications for amputations in sickle cell disease included three distinct categories: mythical beliefs, therapeutic and malpractice. All therapeutic amputations were for severely painful, large, recalcitrant leg ulcers that failed non-interventional therapies. Amputation resulted in pain relief and better quality of life. Phantom neuropathic pain was not a major issue post-operatively. It was absent, transient or well controlled with antidepressants. Limb function was restored post-amputation with prosthetic artificial limbs, wheelchairs or crutches. Malpractice amputations were due to misdiagnosis or to cryotherapy by exposing the painful limb to ice water resulting in thrombosis, gangrene and amputation. We strongly suggest that leg amputations should be considered in the management of certain patients with severe extensive refractory leg ulcers, and topical cryotherapy should never be used to manage sickle cell pain.40150155Office of the Secretary of Health for the State of Rio de JaneiroBrazilian Ministry of HealthSickle Cell Program of the Department of Health of the Commonwealth of Pennsylvania, Harrisburg, PA, US

Expression of inducible nitric oxide synthase is increased in acute myeloid leukaemia

Significant activity of inducible nitric oxide synthase (iNOS) has been reported in tumour cells, including chronic lymphoid leukaemic cells. In this study, we analysed the expression of NOS in 15 untreated patients with acute myeloid leukaemia (AML) and in 7 normal controls. Using flow cytometry and immunocytochemistry, we demonstrated that patients with AML had a high expression of NOS when compared to controls. There was no correlation between the expression of NOS and the expression of p53 and K, H, and N-ras mutation and expression, suggesting that the high expression of NOS is independent of these proteins and could be the result of transcription factors expressed in AML. Copyright (C) 2001 S. Karger AG, Basel.1063959