Efficient expression of CFTR function with adeno-associated virus vectors that carry shortened CFTR genes

Adeno-associated virus (AAV)-based vectors have been shown to be effective in transferring the cystic fibrosis gene (CFTR) into airway epithelial cells in animal models and in patients. However, the level of CFTR gene expression has been low because the vector cannot accommodate the CFTR gene together with a promoter. In this study, we described a strategy to reduce the size of the CFTR cDNA to allow the incorporation of an effective promoter with the CFTR gene into AAV vectors. We engineered and tested 20 CFTR mini-genes containing deletions that were targeted to regions that may contain nonessential sequences. Functional analyses showed that four of the shortened CFTRs (one with combined deletions) retained the function and the characteristics of a wild-type CFTR, as measured by open probability, time voltage dependence, and regulation by cAMP. By using an AAV vector with a P5 promoter, we transduced these short forms of CFTR genes into target cells and demonstrated high levels of CFTR expression. We also demonstrated that smaller AAV/CFTR vectors with a P5 promoter expressed the CFTR gene more efficiently than larger vectors or a vector in which CFTR gene was expressed from the AAV inverted terminal repeat sequence. The CFTR mini-gene with combined deletions was packaged into AAV virions more efficiently, generated higher titers of transducing virions, and more effectively transferred CFTR function into target cells. These new vectors should circumvent the limitations of AAV vector for CFTR expression. Our strategy also may be applicable to other genes, the sizes of which exceed the packaging limit of an AAV vector.     

The production of experimentally labelled aerosols in the sub-micron range

An apparatus for the production of labelled, stable, insoluble particles of ferric oxide in the size range 0·08–0·5 μ is described. The apparatus has a high overall efficiency, and is very suitable for cases when the amount of material to be nebulized is limited.

The characteristics of the particles are examined and the rapid variation of particle density with particle size is studied and explained on a simple semi-empirical theory.     

Oxidative degradation of the carbothioate herbicide, molinate, using nanoscale zero-valent iron

Degradation of the carbothiolate herbicide, molinate, has been investigated in oxic solutions containing nanoscale zero-valent iron particles and found to be effectively degraded by an oxidative pathway. Both ferrous iron and superoxide (or, at pH < 4.8, hydroperoxy) radicals appearto be generated on corrosion of the zero-valent iron with resultant production of strongly oxidizing entities capable of degrading the trace contaminant.     

Die therapeutische Interaktion als moralische Vorgabe

Definition of the problem

Hospitals serve the general purpose to improve the health of patients. Health care professionals are a necessary means to achieve that end but have their own more specific professional ends. What is the due relationship between those kinds of ends with respect to the organisation of hospitals?

Arguments

Individual health care in hospitals is delivered by professionals who are dependent upon the hospital??s human, administrative and technical facilities. As organised social entities, hospitals use professionals as the means to an end we normally call health of patients. More precisely, the professional task consists in a specific, namely, therapeutic interaction, an asymmetric relationship between morally equals. Professionals have to explore, interpret and pursue patients?? interests according to their consent. From a moral perspective, this interaction should be kept free from distortion through external incentives which divert the professional??s intrinsic motivation. Although a professional responsibility, the individual professional would be overcharged with this organisational task.

Conclusion

The profession has a responsibility to protect and foster professional behaviour of its members including participation in organising hospitals and the individual professional should engage in organising the profession as a collective agent.     

Cardiovascular and biochemical evidence of stress during major surgery associated with different techniques of anaesthesia

The relative merits of a potent narcotic and a spinal analgesic to affect the stress response to a standard operation have been assessed. Forty-five fit patients scheduled for abdominal hysterectomy were allocated at random to three groups, referred to as standard (i.v. anaesthesia alone), spinal (spinal plus i.v. anaesthesia) and fentanyl (fentanyl plus i.v. anaesthesia) groups. In the doses used, fentanyl produced the most effective attenuation of the cardiovascular, hormonal and metabolic responses to stress, but had the disadvantage of prolonged respiratory depression. Spinal anaesthesia gave only a modified blockade of the response to stress and did not obtund the response to intubation.     

SEMPA – Ein Ansatz des Semantischen Prozessmanagements zur Planung von Prozessmodellen

Currently process modeling is mostly done manually. Therefore, the initial design of process models as well as changes to process models which are frequently necessary to react to new market developments or new regulations are time-consuming tasks. In this paper we introduce SEMPA, an approach for the partly automatic planning of process models. Using ontologies to semantically describe actions – as envisioned in Semantic Business Process Management –, a process model for a specified problem setting can be created automatically. In comparison to existing planning algorithms our approach creates process models including control structures and is able to cope with complex and numerical input and output parameters of actions. The prototypical implementation as well as an example taken from the financial services domain illustrate the practical benefit of our approach.     

Tools for the job: a report of two surveys of information and communications technology training and use for literacy in primary schools in the West of England

Substantial investment has been made in improving computer hardware and raising the profile of information and communications technology (ICT) in English primary schools in recent years, in line with the belief that skills in ICT are essential for our future workforce ( DfEE/QCA 2000 ). This study compares practising teachers' responses in 1998 and 2001 to a questionnaire about the aims and uses of ICT in primary schools for literacy activities. It discusses the changes in what teachers want and their understanding of the task the government has given them to do. A commonly cited problem is finding time to absorb the new technology to maximise its pedagogic potential.