Use of L-Proline and ATP Production by Trypanosoma cruzi Metacyclic Forms as Requirements for Host Cell Invasion

The process of host cell invasion by Trypanosoma cruzi depends on parasite energy. What source of energy is used for that event is not known. To address this and other questions related to T. cruzi energy requirements and cell invasion, we analyzed metacyclic trypomastigote forms of the phylogenetically distant CL and G strains. For both strains, the nutritional stress experienced by cells starved for 24, 36, or 48 h in phosphate-buffered saline reduced the ATP content and the ability of the parasite to invade HeLa cells proportionally to the starvation time. Inhibition of ATP production by treating parasites with rotenone plus antimycin A also diminished the infectivity. Nutrient depletion did not alter the expression of gp82, the surface molecule that mediates CL strain internalization, but increased the expression of gp90, the negative regulator of cell invasion, in the G strain. When L-proline was given to metacyclic forms starved for 36 h, the ATP levels were restored to those of nonstarved controls for both strains. Glucose had no such effect, although this carbohydrate and L-proline were transported in similar fashions. Recovery of infectivity promoted by L-proline treatment of starved parasites was restricted to the CL strain. The profile of restoration of ATP content and gp82-mediated invasion capacity by L-proline treatment of starved Y-strain parasites was similar to that of the CL strain, whereas the Dm28 and Dm30 strains, whose infectivity is downregulated by gp90, behaved like the G strain. L-Proline was also found to increase the ability of the CL strain to traverse a gastric mucin layer, a property important for the establishment of T. cruzi infection by the oral route. Efficient translocation of parasites through gastric mucin toward the target epithelial cells in the stomach mucosa is an essential requirement for subsequent cell invasion. By relying on these closely associated ATP-driven processes, the metacyclic trypomastigotes effectively accomplish their internalization.

Scheduling Grid Applications with Software Requirements

The aim of task scheduling is to minimize the makespan of applications, exploiting the best possible way to use shared resources. Applications have requirements which call for customized environments for their execution. One way to provide such environments is to use virtualization on demand. This paper presents two schedulers based on integer linear programming which schedule virtual machines (VMs) in grid resources and tasks on these VMs. The schedulers differ from previous work by the joint scheduling of tasks and VMs and by considering the impact of the available bandwidth on the quality of the schedule. Experiments show the efficacy of the schedulers in scenarios with different network configurations.

Insights into the Molecular Requirements for the Anti-obesity Activity of a Series of CB1 Ligands

Two-dimensional and 3D quantitative structure-activity relationships studies were performed on a series of diarylpyridines that acts as cannabinoid receptor ligands by means of hologram quantitative structure-activity relationships and comparative molecular field analysis methods. The quantitative structure-activity relationships models were built using a data set of 52 CB1 ligands that can be used as anti-obesity agents. Significant correlation coefficients (hologram quantitative structure-activity relationships: r 2 = 0.91, q 2 = 0.78; comparative molecular field analysis: r 2 = 0.98, q 2 = 0.77) were obtained, indicating the potential of these 2D and 3D models for untested compounds. The models were then used to predict the potency of an external test set, and the predicted (calculated) values are in good agreement with the experimental results. The final quantitative structure-activity relationships models, along with the information obtained from 2D contribution maps and 3D contour maps, obtained in this study are useful tools for the design of novel CB1 ligands with improved anti-obesity potency.

Mässingslegeringar med låg blyhalt för svarvade komponenter ämnade för dricksvatten

This thesis is about brass alloys with low lead levels for manufacturing of turned components destined for human consumption. Is it technically possible, economically viable and environmentally necessary to produce lead-free brass alloys? Turning tests and leaching tests has been carried out in low-lead brass. The result of the tests carried out show that it is technically possible to produce faucets in low-leaded brass, but since these alloys are harder and less ductile, it takes more power and more cooling when it is processed. There should be more reality-based tests in regular machines that belong in the line of manufacturing. Tests is needed to find out which tool materials, cutting angles, cooling, etc. which are needed to manufacture products with the right surface, dimensions, durability, etc. One thing that no one knows today is the lifetime of a faucet made of low-lead brass. If these faucet’s do not have a higher life than that made in CW 602 N, it is a major strain on nature to produce these in low-lead brass, then to maintain production of the faucets as it is today. No information has come from the Boverket of tougher requirements for lead content in brass. This makes it difficult to know how much effort that is needed to replace lead. A legal requirement or to lose market areas is otherwise a good motivation to move forward.

On Qualitative Probabilities for Legal Reasoning about Evidence

A crucial aspect of evidential reasoning in crime investigation involves comparing the support that evidence provides for alternative hypotheses. Recent work in forensic statistics has shown how Bayesian Networks (BNs) can be employed for this purpose. However, the specification of BNs requires conditional probability tables describing the uncertain processes under evaluation. When these processes are poorly understood, it is necessary to rely on subjective probabilities provided by experts. Accurate probabilities of this type are normally hard to acquire from experts. Recent work in qualitative reasoning has developed methods to perform probabilistic reasoning using coarser representations. However, the latter types of approaches are too imprecise to compare the likelihood of alternative hypotheses. This paper examines this shortcoming of the qualitative approaches when applied to the aforementioned problem, and identifies and integrates techniques to refine them.

Legal LEGO: Model based computer assisted teaching in evidence courses

This paper describes the development of a new approach to the use of ICT for the teaching of courses in the interpretation and evaluation of evidence. It is based on ideas developed for the teaching of science to school children, in particular the importance of models and qualitative reasoning skills. In the first part, we make an analysis of the basis of current research into “evidence scholarship” and the demands such a system would have to meet. In the second part, we introduce the details of such a system that we developed initially to assist police in the interpretation of evidence.

Reasoning about Requirements Evolution Using Clustered Belief Revision

During the development of system requirements, software system specifications are often inconsistent. Inconsistencies may arise for different reasons, for example, when multiple conflicting viewpoints are embodied in the specification, or when the specification itself is at a transient stage of evolution. These inconsistencies cannot always be resolved immediately. As a result, we argue that a formal framework for the analysis of evolving specifications should be able to tolerate inconsistency by allowing reasoning in the presence of inconsistency without trivialisation, and circumvent inconsistency by enabling impact analyses of potential changes to be carried out. This paper shows how clustered belief revision can help in this process. Clustered belief revision allows for the grouping of requirements with similar functionality into clusters and the assignment of priorities between them. By analysing the result of a cluster, an engineer can either choose to rectify problems in the specification or to postpone the changes until more information becomes available.

The Requirements of Using Provenance in e-Science Experiments

In e-Science experiments, it is vital to record the experimental process for later use such as in interpreting results, verifying that the correct process took place or tracing where data came from. The process that led to some data is called the provenance of that data, and a provenance architecture is the software architecture for a system that will provide the necessary functionality to record, store and use process documentation. However, there has been little principled analysis of what is actually required of a provenance architecture, so it is impossible to determine the functionality they would ideally support. In this paper, we present use cases for a provenance architecture from current experiments in biology, chemistry, physics and computer science, and analyse the use cases to determine the technical requirements of a generic, technology and application-independent architecture. We propose an architecture that meets these requirements and evaluate a preliminary implementation by attempting to realise two of the use cases.

Requirements for Provenance on the Web

From where did this tweet originate? Was this quote from the New York Times modified? Daily, we rely on data from the Web but often it is difficult or impossible to determine where it came from or how it was produced. This lack of provenance is particularly evident when people and systems deal with Web information or with any environment where information comes from sources of varying quality. Provenance is not captured pervasively in information systems. There are major technical, social, and economic impediments that stand in the way of using provenance effectively. This paper synthesizes requirements for provenance on the Web for a number of dimensions focusing on three key aspects of provenance: the content of provenance, the management of provenance records, and the uses of provenance information. To illustrate these requirements, we use three synthesized scenarios that encompass provenance problems faced by Web users today.