An integrated approach of software development and test processes to distributed teams

The Distributed Software Development (DSD) is a development strategy that meets the globalization needs concerned with the increase productivity and cost reduction. However, the temporal distance, geographical dispersion and the socio-cultural differences, increased some challenges and, especially, added new requirements related with the communication, coordination and control of projects. Among these new demands there is the necessity of a software process that provides adequate support to the distributed software development. This paper presents an integrated approach of software development and test that considers distributed teams peculiarities. The approach purpose is to offer support to DSD, providing a better project visibility, improving the communication between the development and test teams, minimizing the ambiguity and difficulty to understand the artifacts and activities. This integrated approach was conceived based on four pillars: (i) to identify the DSD peculiarities concerned with development and test processes, (ii) to define the necessary elements to compose the integrated approach of development and test to support the distributed teams, (iii) to describe and specify the workflows, artifacts, and roles of the approach, and (iv) to represent appropriately the approach to enable the effective communication and understanding of it.

Effectiveness of the polysaccharide pneumococcal vaccine among HIV-infected persons in Brazil: a case control study

Abstract Background Polysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population. The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil. Methods A case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview. Results After adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI: <0 to 62%). Conclusion We were unable to demonstrate a statistically significant protective effect of 23 valent polysaccharide against invasive pneumococcal infection vaccine among HIV-infected adults in Brazil. While the vaccine is relatively inexpensive and safe, its effectiveness among HIV-infected adults in Brazil is uncertain.

Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

Abstract Background Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R)-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC) on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170). These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT) and B16F10 melanoma. Methods Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2), caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF) and prostaglandin E2 (PGE2) were determined by ELISA, and levels of nitric oxide (NO) by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry. Results Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by in vivo pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained the cells from inside the tumour, but not the tumour cells grown in vitro. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R. Conclusions We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours.

Use of passive diffusion sampling method for defining NO2 concentrations gradient in São Paulo, Brazil

Abstract Background Air pollution in São Paulo is constantly being measured by the State of Sao Paulo Environmental Agency, however there is no information on the variation between places with different traffic densities. This study was intended to identify a gradient of exposure to traffic-related air pollution within different areas in São Paulo to provide information for future epidemiological studies. Methods We measured NO2 using Palmes' diffusion tubes in 36 sites on streets chosen to be representative of different road types and traffic densities in São Paulo in two one-week periods (July and August 2000). In each study period, two tubes were installed in each site, and two additional tubes were installed in 10 control sites. Results Average NO2 concentrations were related to traffic density, observed on the spot, to number of vehicles counted, and to traffic density strata defined by the city Traffic Engineering Company (CET). Average NO2concentrations were 63μg/m3 and 49μg/m3 in the first and second periods, respectively. Dividing the sites by the observed traffic density, we found: heavy traffic (n = 17): 64μg/m3 (95% CI: 59μg/m3 – 68μg/m3); local traffic (n = 16): 48μg/m3 (95% CI: 44μg/m3 – 52μg/m3) (p < 0.001). Conclusion The differences in NO2 levels between heavy and local traffic sites are large enough to suggest the use of a more refined classification of exposure in epidemiological studies in the city. Number of vehicles counted, traffic density observed on the spot and traffic density strata defined by the CET might be used as a proxy for traffic exposure in São Paulo when more accurate measurements are not available.

PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes

Abstract Background Pituitary tumor transforming gene (pttg) is a novel oncogene that is expressed at higher level in most of the tumors analyzed to date compared to normal tissues. Nevertheless, its expression in prolactinomas and its relation with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to determine the pituitary level of pttg in three different experimental models of prolactinomas with altered dopaminergic control of the pituitary: the dopaminergic D2R knockout female mouse, the estrogen-treated rat, and the senescent female rat. These three models shared the characteristics of increased pituitary weight, hyperprolactinemia, lactotrope hyperplasia and reduced or absent dopaminergic action at the pituitary level. We also studied samples from human macroprolactinomas, which were characterized as responsive or resistant to dopamine agonist therapy. Results When compared to female wild-type mice, pituitaries from female D2R knockout mice had decreased PTTG concentration, while no difference in pttg mRNA level was found. In senescent rats no difference in pituitary PTTG protein expression was found when compared to young rats. But, in young female rats treated with a synthetic estrogen (Diethylstylbestrol, 20 mg) PTTG protein expression was enhanced (P = 0.029). Therefore, in the three experimental models of prolactinomas, pituitary size was increased and there was hyperprolactinemia, but PTTG levels followed different patterns. Patients with macroprolactinomas were divided in those in which dopaminergic therapy normalized or failed to normalize prolactin levels (responsive and resistant, respectively). When pituitary pttg mRNA level was analyzed in these macroprolactinomas, no differences were found. We next analyzed estrogen action at the pituitary by measuring pituitary estrogen receptor α levels. The D2R knockout female mice have low estrogen levels and in accordance, pituitary estrogen receptors were increased (P = 0.047). On the other hand, in senescent rats estrogen levels were slightly though not significantly higher, and estrogen receptors were similar between groups. The estrogen-treated rats had high pharmacological levels of the synthetic estrogen, and estrogen receptors were markedly lower than in controls (P < 0.0001). Finally, in patients with dopamine resistant or responsive prolactinomas no significant differences in estrogen receptor α levels were found. Therefore, pituitary PTTG was increased only if estrogen action was increased, which correlated with a decrease in pituitary estrogen receptor level. Conclusion We conclude that PTTG does not correlate with prolactin levels or tumor size in animal models of prolactinoma, and its pituitary content is not related to a decrease in dopaminergic control of the lactotrope, but may be influenced by estrogen action at the pituitary level. Therefore it is increased only in prolactinomas generated by estrogen treatment, and not in prolactinomas arising from deficient dopamine control, or in dopamine resistant compared with dopamine responsive human prolactinomas. These results are important in the search for reliable prognostic indicators for patients with pituitary adenomas which will make tumor-specific therapy possible, and help to elucidate the poorly understood phenomenon of pituitary tumorigenesis.

The need of a weight management control program in judo: a proposal based on the successful case of wrestling

Judo competitions are divided into weight classes. However, most athletes reduce their body weight in a few days before competition in order to obtain a competitive advantage over lighter opponents. To achieve fast weight reduction, athletes use a number of aggressive nutritional strategies so many of them place themselves at a high health-injury risk. In collegiate wrestling, a similar problem has been observed and three wrestlers died in 1997 due to rapid weight loss regimes. After these deaths, the National Collegiate Athletic Association had implemented a successful weight management program which was proven to improve weight management behavior. No similar program has ever been discussed by judo federations even though judo competitors present a comparable inappropriate pattern of weight control. In view of this, the basis for a weight control program is provided in this manuscript, as follows: competition should begin within 1 hour after weigh-in, at the latest; each athlete is allowed to be weighed-in only once; rapid weight loss as well as artificial rehydration (i.e., saline infusion) methods are prohibited during the entire competition day; athletes should pass the hydration test to get their weigh-in validated; an individual minimum competitive weight (male athletes competing at no less than 7% and females at no less than 12% of body fat) should be determined at the beginning of each season; athletes are not allowed to compete in any weight class that requires weight reductions greater than 1.5% of body weight per week. In parallel, educational programs should aim at increasing the athletes', coaches' and parents' awareness about the risks of aggressive nutritional strategies as well as healthier ways to properly manage body weight.

A Robust Structural PGN Model for Control of Cell-Cycle Progression Stabilized by Negative Feedbacks

The cell division cycle comprises a sequence of phenomena controlled by a stable and robust genetic network. We applied a probabilistic genetic network (PGN) to construct a hypothetical model with a dynamical behavior displaying the degree of robustness typical of the biological cell cycle. The structure of our PGN model was inspired in well-established biological facts such as the existence of integrator subsystems, negative and positive feedback loops, and redundant signaling pathways. Our model represents genes interactions as stochastic processes and presents strong robustness in the presence of moderate noise and parameters fluctuations. A recently published deterministic yeast cell-cycle model does not perform as well as our PGN model, even upon moderate noise conditions. In addition, self stimulatory mechanisms can give our PGN model the possibility of having a pacemaker activity similar to the observed in the oscillatory embryonic cell cycle.

The promoter of filamentation (POF1) protein from Saccharomyces cerevisiae is an ATPase involved in the protein quality control process

Background: The gene YCL047C, which has been renamed promoter of filamentation gene (POF1), has recently been described as a cell component involved in yeast filamentous growth. The objective of this work is to understand the molecular and biological function of this gene. Results: Here, we report that the protein encoded by the POF1 gene, Pof1p, is an ATPase that may be part of the Saccharomyces cerevisiae protein quality control pathway. According to the results, Δpof1 cells showed increased sensitivity to hydrogen peroxide, tert-butyl hydroperoxide, heat shock and protein unfolding agents, such as dithiothreitol and tunicamycin. Besides, the overexpression of POF1 suppressed the sensitivity of Δpct1, a strain that lacks a gene that encodes a phosphocholine cytidylyltransferase, to heat shock. In vitro analysis showed, however, that the purified Pof1p enzyme had no cytidylyltransferase activity but does have ATPase activity, with catalytic efficiency comparable to other ATPases involved in endoplasmic reticulum-associated degradation of proteins (ERAD). Supporting these findings, co-immunoprecipitation experiments showed a physical interaction between Pof1p and Ubc7p (an ubiquitin conjugating enzyme) in vivo. Conclusions: Taken together, the results strongly suggest that the biological function of Pof1p is related to the regulation of protein degradation.

Development of a molecular platform for HTLV confirmatory diagnosis: importance of the internal amplification control

Finnancial Support: CTC/INCTC, FAPESP, FUNDHERP, FINEP.

The Brazilian Network for HIV-1 Genotyping External Quality Control Assurance Programme

The Brazilian network for genotyping is composed of 21 laboratories that perform and analyze genotyping tests for all HIV-infected patients within the public system, performing approximately 25,000 tests per year. We assessed the interlaboratory and intralaboratory reproducibility of genotyping systems by creating and implementing a local external quality control evaluation. Plasma samples from HIV-1-infected individuals (with low and intermediate viral loads) or RNA viral constructs with specific mutations were used. This evaluation included analyses of sensitivity and specificity of the tests based on qualitative and quantitative criteria, which scored laboratory performance on a 100-point system. Five evaluations were performed from 2003 to 2008, with 64% of laboratories scoring over 80 points in 2003, 81% doing so in 2005, 56% in 2006, 91% in 2007, and 90% in 2008 (Kruskal-Wallis, p = 0.003). Increased performance was aided by retraining laboratories that had specific deficiencies. The results emphasize the importance of investing in laboratory training and interpretation of DNA sequencing results, especially in developing countries where public (or scarce) resources are used to manage the AIDS epidemic.

Heme oxygenase-1 activity is involved in the control of Toxoplasma gondii infection in the lung of BALB/c and C57BL/6 and in the small intestine of C57BL/6 mice

Heme oxygenase-1 (HO-1) is an enzyme that catabolizes free heme, which induces an intense inflammatory response. The expression of HO-1 is induced by different stimuli, triggering an anti-inflammatory response during biological stress. It was previously verified that HO-1 is able to induce indoleamine 2,3-dioxygenase (IDO), an enzyme that is induced by IFN-γ in Toxoplasma gondii infection. To verify the role of HO-1 during in vivo T. gondii infection, BALB/c and C57BL/6 mice were infected with the ME49 strain and treated with zinc protoporphyrin IX (ZnPPIX) or hemin, which inhibit or induce HO-1 activity, respectively. The results show that T. gondii infection induced high levels of HO-1 expression in the lung of BALB/c and C57BL6 mice. The animals treated with ZnPPIX presented higher parasitism in the lungs of both lineages of mice, whereas hemin treatment decreased the parasite replication in this organ and in the small intestine of infected C57BL/6 mice. Furthermore, C57BL/6 mice infected with T. gondii and treated with hemin showed higher levels of IDO expression in the lungs and small intestine than uninfected mice. In conclusion, our data suggest that HO-1 activity is involved in the control of T. gondii in the lungs of both mouse lineages, whereas the hemin, a HO-1 inducer, seems to be involved in the control of parasitism in the small intestine of C57BL/6 mice.

Design and control techniques of optical networks

The world of communication has changed quickly in the last decade resulting in the the rapid increase in the pace of peoples’ lives. This is due to the explosion of mobile communication and the internet which has now reached all levels of society. With such pressure for access to communication there is increased demand for bandwidth. Photonic technology is the right solution for high speed networks that have to supply wide bandwidth to new communication service providers. In particular this Ph.D. dissertation deals with DWDM optical packet-switched networks. The issue introduces a huge quantity of problems from physical layer up to transport layer. Here this subject is tackled from the network level perspective. The long term solution represented by optical packet switching has been fully explored in this years together with the Network Research Group at the department of Electronics, Computer Science and System of the University of Bologna. Some national as well as international projects supported this research like the Network of Excellence (NoE) e-Photon/ONe, funded by the European Commission in the Sixth Framework Programme and INTREPIDO project (End-to-end Traffic Engineering and Protection for IP over DWDM Optical Networks) funded by the Italian Ministry of Education, University and Scientific Research. Optical packet switching for DWDM networks is studied at single node level as well as at network level. In particular the techniques discussed are thought to be implemented for a long-haul transport network that connects local and metropolitan networks around the world. The main issues faced are contention resolution in a asynchronous variable packet length environment, adaptive routing, wavelength conversion and node architecture. Characteristics that a network must assure as quality of service and resilience are also explored at both node and network level. Results are mainly evaluated via simulation and through analysis.

Motion control and real-time systems: an approach to trajectory rebuilding in non-deterministic networks

Motion control is a sub-field of automation, in which the position and/or velocity of machines are controlled using some type of device. In motion control the position, velocity, force, pressure, etc., profiles are designed in such a way that the different mechanical parts work as an harmonious whole in which a perfect synchronization must be achieved. The real-time exchange of information in the distributed system that is nowadays an industrial plant plays an important role in order to achieve always better performance, better effectiveness and better safety. The network for connecting field devices such as sensors, actuators, field controllers such as PLCs, regulators, drive controller etc., and man-machine interfaces is commonly called fieldbus. Since the motion transmission is now task of the communication system, and not more of kinematic chains as in the past, the communication protocol must assure that the desired profiles, and their properties, are correctly transmitted to the axes then reproduced or else the synchronization among the different parts is lost with all the resulting consequences. In this thesis, the problem of trajectory reconstruction in the case of an event-triggered communication system is faced. The most important feature that a real-time communication system must have is the preservation of the following temporal and spatial properties: absolute temporal consistency, relative temporal consistency, spatial consistency. Starting from the basic system composed by one master and one slave and passing through systems made up by many slaves and one master or many masters and one slave, the problems in the profile reconstruction and temporal properties preservation, and subsequently the synchronization of different profiles in network adopting an event-triggered communication system, have been shown. These networks are characterized by the fact that a common knowledge of the global time is not available. Therefore they are non-deterministic networks. Each topology is analyzed and the proposed solution based on phase-locked loops adopted for the basic master-slave case has been improved to face with the other configurations.

Design of optical networks for advanced applications

Nowadays, computing is migrating from traditional high performance and distributed computing to pervasive and utility computing based on heterogeneous networks and clients. The current trend suggests that future IT services will rely on distributed resources and on fast communication of heterogeneous contents. The success of this new range of services is directly linked to the effectiveness of the infrastructure in delivering them. The communication infrastructure will be the aggregation of different technologies even though the current trend suggests the emergence of single IP based transport service. Optical networking is a key technology to answer the increasing requests for dynamic bandwidth allocation and configure multiple topologies over the same physical layer infrastructure, optical networks today are still “far” from accessible from directly configure and offer network services and need to be enriched with more “user oriented” functionalities. However, current Control Plane architectures only facilitate efficient end-to-end connectivity provisioning and certainly cannot meet future network service requirements, e.g. the coordinated control of resources. The overall objective of this work is to provide the network with the improved usability and accessibility of the services provided by the Optical Network. More precisely, the definition of a service-oriented architecture is the enable technology to allow user applications to gain benefit of advanced services over an underlying dynamic optical layer. The definition of a service oriented networking architecture based on advanced optical network technologies facilitates users and applications access to abstracted levels of information regarding offered advanced network services. This thesis faces the problem to define a Service Oriented Architecture and its relevant building blocks, protocols and languages. In particular, this work has been focused on the use of the SIP protocol as a inter-layers signalling protocol which defines the Session Plane in conjunction with the Network Resource Description language. On the other hand, an advantage optical network must accommodate high data bandwidth with different granularities. Currently, two main technologies are emerging promoting the development of the future optical transport network, Optical Burst and Packet Switching. Both technologies respectively promise to provide all optical burst or packet switching instead of the current circuit switching. However, the electronic domain is still present in the scheduler forwarding and routing decision. Because of the high optics transmission frequency the burst or packet scheduler faces a difficult challenge, consequentially, high performance and time focused design of both memory and forwarding logic is need. This open issue has been faced in this thesis proposing an high efficiently implementation of burst and packet scheduler. The main novelty of the proposed implementation is that the scheduling problem has turned into simple calculation of a min/max function and the function complexity is almost independent of on the traffic conditions.

Coordinated Control of Robotic Swarms in Unknown Environments

This thesis gathers the work carried out by the author in the last three years of research and it concerns the study and implementation of algorithms to coordinate and control a swarm of mobile robots moving in unknown environments. In particular, the author's attention is focused on two different approaches in order to solve two different problems. The first algorithm considered in this work deals with the possibility of decomposing a main complex task in many simple subtasks by exploiting the decentralized implementation of the so called \emph{Null Space Behavioral} paradigm. This approach to the problem of merging different subtasks with assigned priority is slightly modified in order to handle critical situations that can be detected when robots are moving through an unknown environment. In fact, issues can occur when one or more robots got stuck in local minima: a smart strategy to avoid deadlock situations is provided by the author and the algorithm is validated by simulative analysis. The second problem deals with the use of concepts borrowed from \emph{graph theory} to control a group differential wheel robots by exploiting the Laplacian solution of the consensus problem. Constraints on the swarm communication topology have been introduced by the use of a range and bearing platform developed at the Distributed Intelligent Systems and Algorithms Laboratory (DISAL), EPFL (Lausanne, CH) where part of author's work has been carried out. The control algorithm is validated by demonstration and simulation analysis and, later, is performed by a team of four robots engaged in a formation mission. To conclude, the capabilities of the algorithm based on the local solution of the consensus problem for differential wheel robots are demonstrated with an application scenario, where nine robots are engaged in a hunting task.