Lymphocyte transformation assay for C neoformans antigen is not reliable for detecting cellular impairment in patients with Neurocryptococcosis

Background: Cryptococcus neoformans causes meningitis and disseminated infection in healthy individuals, but more commonly in hosts with defective immune responses. Cell-mediated immunity is an important component of the immune response to a great variety of infections, including yeast infections. We aimed to evaluate a specific lymphocyte transformation assay to Cryptococcus neoformans in order to identify immunodeficiency associated to neurocryptococcosis (NCC) as primary cause of the mycosis. Methods: Healthy volunteers, poultry growers, and HIV-seronegative patients with neurocryptococcosis were tested for cellular immune response. Cryptococcal meningitis was diagnosed by India ink staining of cerebrospinal fluid and cryptococcal antigen test (Immunomycol-Inc, SP, Brazil). Isolated peripheral blood mononuclear cells were stimulated with C. neoformans antigen, C. albicans antigen, and pokeweed mitogen. The amount of H-3-thymidine incorporated was assessed, and the results were expressed as stimulation index (SI) and log SI, sensitivity, specificity, and cut-off value (receiver operating characteristics curve). We applied unpaired Student t tests to compare data and considered significant differences for p<0.05. Results: The lymphotoxin alpha showed a low capacity with all the stimuli for classifying patients as responders and non-responders. Lymphotoxin alpha stimulated by heated-killed antigen from patients with neurocryptococcosis was not affected by TCD4+ cell count, and the intensity of response did not correlate with the clinical evolution of neurocryptococcosis. Conclusion: Response to lymphocyte transformation assay should be analyzed based on a normal range and using more than one stimulator. The use of a cut-off value to classify patients with neurocryptococcosis is inadequate. Statistical analysis should be based on the log transformation of SI. A more purified antigen for evaluating specific response to C. neoformans is needed.

Genetic transformation of three sweet orange cultivars from explants of adult plants

The difficulty in adult tissue genetic transformation in woody species is still an obstacle to be overcome, including in most sweet orange cultivars of the Brazilian citrus industry. This work reports that, after in vitro culture adjustments, transgenic adventitious buds of 'Hamlin', 'Pra', and 'Valencia' sweet oranges (Citrus sinensis L. Osbeck) were recovered using adult material as explant source, in genetic transformation experiments via Agrobacterium tumefaciens. The transgenic buds were identified by the GUS histochemical analysis and confirmed by PCR analysis, which indicated the presence of an amplified fragment of 817 bp corresponding to the uidA gene sequence. The efficiencies of genetic transformation for 'Hamlin', 'Pra', and 'Valencia' sweet orange cultivars were 2.5, 1.4, and 3.7%, respectively. Media supplemented with auxins and cytokinins during co-culture, and media with high concentrations of cytokinins (3 mg L-1) during transgenic selection led to the transformation and, consequently, the regeneration of adequate number of adventitious buds for the three cultivars. The use of sonication during the explant disinfection was not effective to reduce endophytic contamination and reduced transformation efficiency.

BCL2A1a Over-Expression in Murine Hematopoietic Stem and Progenitor Cells Decreases Apoptosis and Results in Hematopoietic Transformation

We previously reported the development of a lethal myeloid sarcoma in a non-human primate model utilizing retroviral vectors to genetically modify hematopoietic stem and progenitor cells. This leukemia was characterized by insertion of the vector provirus into the BCL2A1 gene, with resultant BCL2A1 over-expression. There is little information on the role of this anti-apoptotic member of the BCL2 family in hematopoiesis or leukemia induction. Therefore we studied the impact of Bcl2a1a lentiviral over-expression on murine hematopoietic stem and progenitor cells. We demonstrated the anti-apoptotic function of this protein in hematopoietic cells, but did not detect any impact of Bcl2a1a on in vitro cell growth or cell cycle kinetics. In vivo, we showed a higher propensity of HSCs over-expressing Bcl2a1a to engraft and contribute to hematopoiesis. Mice over-expressing Bcl2a1a in the hematologic compartment eventually developed an aggressive malignant disease characterized as a leukemia/lymphoma of B-cell origin. Secondary transplants carried out to investigate the primitive origin of the disease revealed the leukemia was transplantable. Thus, Bcl2a1 should be considered as a protooncogene with a potential role in both lymphoid and myeloid leukemogenesis, and a concerning site for insertional activation by integrating retroviral vectors utilized in hematopoietic stem cell gene therapy.

Fungal Transformation and Schistosomicidal Effects of Pimaradienoic Acid

The schistosomicidal effects of pimaradienoic acid (PA) and two derivatives, obtained by fungal transformation in the presence of Aspergillus ochraceus, were investigated. PA was the only compound with antischistosomal activity among the three diterpenes studied, with the ability to significantly reduce the viability of the parasites at concentrations ranging from 25 to 100 mu M. PA also promoted morphological alterations of the tegument of Schistosoma mansoni, separated all the worm couples, and affected the production and development of eggs. Moreover, this compound was devoid of toxicity toward human fibroblasts. In a preliminary in vivo experiment, PA at a dose of 100 mg/kg significantly diminished the number of parasites in infected Balb/c mice. Taken together, these results show that PA may be potentially employed in the discovery of novel schistosomicidal agents, and that diterpenes are an important class of natural compounds for the investigation of agents capable of fighting the parasite responsible for human schistosomiasis.

Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus

The biotransformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus MT 5.3 yielded a rare derivative that was elucidated by spectrometric methods. The fungus led to the formation of a different product through an unusual epoxidation reaction between C4 and C5, formation of a C3,C10 ether bridge, and a methoxylation of the C1 of tagitinin C. The chemical structure of the product, namely 1 beta-methoxy-3 alpha-hydroxy-3,10 beta-4,5 alpha-diepoxy-8 beta-isobutyroyloxygermacr-11(13)-en-6 alpha,12-olide, is the same as that of a derivative that was recently isolated from the flowers of a Brazilian population of Mexican sunflower (Tithonia diversifolia), which is the source of the substrate tagitinin C. The in vitro cytotoxic activity of the substrate and the biotransformed product were evaluated in HL-60 cells using an MTT assay, and both compounds were found to be cytotoxic. We show that soil fungi may be useful in the biotransformation of sesquiterpene lactones, thereby leading to unusual changes in their chemical structures that may preserve or alter their biological activities, and may also mimic plant biosynthetic pathways for production of secondary metabolites.

Spectral behavior of some modal soil profiles from São Paulo State, Brazil

Remote sensing has a high potential for environmental evaluation. However, a necessity exists for a better understanding of the relations between the soil attributes and spectral data. The objective of this work was to analyze the spectral behavior of some soil profiles from the region of Piracicaba, São Paulo State, using a laboratory spectroradiometer (400 to 2500 nm). The relations between the reflected electromagnetic energy and the soil physical, chemical and mineralogical attributes were analyzed, verifying the spectral variations of soil samples in depth along the profiles with their classification and discrimination. Sandy soil reflected more, presenting a spectral curve with an ascendant form, opposite to clayey soils. The 1900 nm band discriminated soil with 2:1 mineralogy from the 1:1 and oxidic soils. It was possible to detect the presence of kaolinite, gibbsite, hematite and goethite in the soils through the descriptive aspects of curves, absorption features and reflectance intensity. A relation exists between the weathering stage and spectral data. The evaluation of the superficial and subsuperficial horizon samples allowed characterizing and discriminating the analytical variability of the profile, helping to soil distinguishing and classification.

QuMinS: fast and scalable querying, mining and summarizing multi-modal databases

Given a large image set, in which very few images have labels, how to guess labels for the remaining majority? How to spot images that need brand new labels different from the predefined ones? How to summarize these data to route the user’s attention to what really matters? Here we answer all these questions. Specifically, we propose QuMinS, a fast, scalable solution to two problems: (i) Low-labor labeling (LLL) – given an image set, very few images have labels, find the most appropriate labels for the rest; and (ii) Mining and attention routing – in the same setting, find clusters, the top-'N IND.O' outlier images, and the 'N IND.R' images that best represent the data. Experiments on satellite images spanning up to 2.25 GB show that, contrasting to the state-of-the-art labeling techniques, QuMinS scales linearly on the data size, being up to 40 times faster than top competitors (GCap), still achieving better or equal accuracy, it spots images that potentially require unpredicted labels, and it works even with tiny initial label sets, i.e., nearly five examples. We also report a case study of our method’s practical usage to show that QuMinS is a viable tool for automatic coffee crop detection from remote sensing images.

Incorporating IT & AT Convergence into Lean Thinking/Six Sigma via the Smarter Operation Transformation (SOT) Methodology

The growing demands for industrial products are imposing an increasingly intense level of competitiveness on the industrial operations. In the meantime, the convergence of information technology (IT) and automation technology (AT) is showing itself to be a tool of great potential for the modernization and improvement of industrial plants. However, for this technology fully to achieve its potential, several obstacles need to be overcome, including the demonstration of the reasoning behind estimations of benefits, investments and risks used to plan the implementation of corporative technology solutions. This article focuses on the evolutionary development of planning and adopting processes of IT & AT convergence. It proposes the incorporation of IT & AT convergence practices into Lean Thinking/Six Sigma, via the method used for planning the convergence of technological activities, known as the Smarter Operation Transformation (SOT) methodology. This article illustrates the SOT methodology through its application in a Brazilian company in the sector of consumer goods. In this application, it is shown that with IT & AT convergence is possible with low investment, in order to reduce the risk of not achieving the goals of key indicators.

Metachronic malignant transformation of small bowel and rectal endometriosis in the same patient

[ES] Background: Malignant transformation of intestinal endometriosis is a rare event with an unknown rate of incidence. Metachronous progression of endometriosis to adenocarcinoma from two distant intestinal foci happening in the same patient has not been previously reported. Case presentation: We describe a case of metachronic transformation of ileal and rectal endometriosis into an adenocarcinoma occurring in a 45-year-old female without macroscopic pelvic involvement of her endometriosis. First, a right colectomy was performed due to intestinal obstruction by an ileal mass. Pathological examination revealed an ileal endometrioid adenocarcinoma and contiguous microscopic endometriotic foci. Twenty months later, a rectal mass was discovered. An endoscopic biopsy revealed an adenocarcinoma. En bloc anterior rectum resection, hysterectomy and bilateral salpingectomy were performed. A second endometrioid adenocarcinoma arising from a focus of endometriosis within the wall of the rectum was diagnosed. Conclusion: Intestinal endometriosis should be considered a premalignant condition in premenopausal women.

Modal hedges in para-pharmaceutical product instructions: some examples from English and Serbian

[EN] The paper investigates how modal hedges (Coates 1983) understood as expressions of procedural meaning , i.e. expressions which instruct the addressee/reader how to process the propositional content of an utterance/statement (Watts 2004) are used in product descriptions, advertisements and consumer instructions leaflets for a number of products belonging to the Consumer Health Care category for the purposes of complying with consumer protection laws on the one hand and serving as an implicit disclaimer of manufacturer’s responsibility on the other. The analysis is carried out contrastively for two languages, English and Serbian. The results obtained are discussed and viewed as a matter of cultural variety and difference, especially taking into consideration the fact that consumer protection laws seem to be equally strict in US, UK and Commonwealth, Europe and Serbia.

Calculation of the eigenfunctions of the two-group neutron diffusion equation and application to modal decomposition of BWR instabilities

In this thesis, numerical methods aiming at determining the eigenfunctions, their adjoint and the corresponding eigenvalues of the two-group neutron diffusion equations representing any heterogeneous system are investigated. First, the classical power iteration method is modified so that the calculation of modes higher than the fundamental mode is possible. Thereafter, the Explicitly-Restarted Arnoldi method, belonging to the class of Krylov subspace methods, is touched upon. Although the modified power iteration method is a computationally-expensive algorithm, its main advantage is its robustness, i.e. the method always converges to the desired eigenfunctions without any need from the user to set up any parameter in the algorithm. On the other hand, the Arnoldi method, which requires some parameters to be defined by the user, is a very efficient method for calculating eigenfunctions of large sparse system of equations with a minimum computational effort. These methods are thereafter used for off-line analysis of the stability of Boiling Water Reactors. Since several oscillation modes are usually excited (global and regional oscillations) when unstable conditions are encountered, the characterization of the stability of the reactor using for instance the Decay Ratio as a stability indicator might be difficult if the contribution from each of the modes are not separated from each other. Such a modal decomposition is applied to a stability test performed at the Swedish Ringhals-1 unit in September 2002, after the use of the Arnoldi method for pre-calculating the different eigenmodes of the neutron flux throughout the reactor. The modal decomposition clearly demonstrates the excitation of both the global and regional oscillations. Furthermore, such oscillations are found to be intermittent with a time-varying phase shift between the first and second azimuthal modes.

Interactions between normative systems and software cognitive agents. A formalization in temporal modal defeasible logic and its implementation

Sustainable computer systems require some flexibility to adapt to environmental unpredictable changes. A solution lies in autonomous software agents which can adapt autonomously to their environments. Though autonomy allows agents to decide which behavior to adopt, a disadvantage is a lack of control, and as a side effect even untrustworthiness: we want to keep some control over such autonomous agents. How to control autonomous agents while respecting their autonomy? A solution is to regulate agents’ behavior by norms. The normative paradigm makes it possible to control autonomous agents while respecting their autonomy, limiting untrustworthiness and augmenting system compliance. It can also facilitate the design of the system, for example, by regulating the coordination among agents. However, an autonomous agent will follow norms or violate them in some conditions. What are the conditions in which a norm is binding upon an agent? While autonomy is regarded as the driving force behind the normative paradigm, cognitive agents provide a basis for modeling the bindingness of norms. In order to cope with the complexity of the modeling of cognitive agents and normative bindingness, we adopt an intentional stance. Since agents are embedded into a dynamic environment, things may not pass at the same instant. Accordingly, our cognitive model is extended to account for some temporal aspects. Special attention is given to the temporal peculiarities of the legal domain such as, among others, the time in force and the time in efficacy of provisions. Some types of normative modifications are also discussed in the framework. It is noteworthy that our temporal account of legal reasoning is integrated to our commonsense temporal account of cognition. As our intention is to build sustainable reasoning systems running unpredictable environment, we adopt a declarative representation of knowledge. A declarative representation of norms will make it easier to update their system representation, thus facilitating system maintenance; and to improve system transparency, thus easing system governance. Since agents are bounded and are embedded into unpredictable environments, and since conflicts may appear amongst mental states and norms, agent reasoning has to be defeasible, i.e. new pieces of information can invalidate formerly derivable conclusions. In this dissertation, our model is formalized into a non-monotonic logic, namely into a temporal modal defeasible logic, in order to account for the interactions between normative systems and software cognitive agents.

Constraint handling rules. Compositional semantics and program transformation

This thesis intends to investigate two aspects of Constraint Handling Rules (CHR). It proposes a compositional semantics and a technique for program transformation. CHR is a concurrent committed-choice constraint logic programming language consisting of guarded rules, which transform multi-sets of atomic formulas (constraints) into simpler ones until exhaustion [Frü06] and it belongs to the declarative languages family. It was initially designed for writing constraint solvers but it has recently also proven to be a general purpose language, being as it is Turing equivalent [SSD05a]. Compositionality is the first CHR aspect to be considered. A trace based compositional semantics for CHR was previously defined in [DGM05]. The reference operational semantics for such a compositional model was the original operational semantics for CHR which, due to the propagation rule, admits trivial non-termination. In this thesis we extend the work of [DGM05] by introducing a more refined trace based compositional semantics which also includes the history. The use of history is a well-known technique in CHR which permits us to trace the application of propagation rules and consequently it permits trivial non-termination avoidance [Abd97, DSGdlBH04]. Naturally, the reference operational semantics, of our new compositional one, uses history to avoid trivial non-termination too. Program transformation is the second CHR aspect to be considered, with particular regard to the unfolding technique. Said technique is an appealing approach which allows us to optimize a given program and in more detail to improve run-time efficiency or spaceconsumption. Essentially it consists of a sequence of syntactic program manipulations which preserve a kind of semantic equivalence called qualified answer [Frü98], between the original program and the transformed ones. The unfolding technique is one of the basic operations which is used by most program transformation systems. It consists in the replacement of a procedure-call by its definition. In CHR every conjunction of constraints can be considered as a procedure-call, every CHR rule can be considered as a procedure and the body of said rule represents the definition of the call. While there is a large body of literature on transformation and unfolding of sequential programs, very few papers have addressed this issue for concurrent languages. We define an unfolding rule, show its correctness and discuss some conditions in which it can be used to delete an unfolded rule while preserving the meaning of the original program. Finally, confluence and termination maintenance between the original and transformed programs are shown. This thesis is organized in the following manner. Chapter 1 gives some general notion about CHR. Section 1.1 outlines the history of programming languages with particular attention to CHR and related languages. Then, Section 1.2 introduces CHR using examples. Section 1.3 gives some preliminaries which will be used during the thesis. Subsequentely, Section 1.4 introduces the syntax and the operational and declarative semantics for the first CHR language proposed. Finally, the methodologies to solve the problem of trivial non-termination related to propagation rules are discussed in Section 1.5. Chapter 2 introduces a compositional semantics for CHR where the propagation rules are considered. In particular, Section 2.1 contains the definition of the semantics. Hence, Section 2.2 presents the compositionality results. Afterwards Section 2.3 expounds upon the correctness results. Chapter 3 presents a particular program transformation known as unfolding. This transformation needs a particular syntax called annotated which is introduced in Section 3.1 and its related modified operational semantics !0t is presented in Section 3.2. Subsequently, Section 3.3 defines the unfolding rule and prove its correctness. Then, in Section 3.4 the problems related to the replacement of a rule by its unfolded version are discussed and this in turn gives a correctness condition which holds for a specific class of rules. Section 3.5 proves that confluence and termination are preserved by the program modifications introduced. Finally, Chapter 4 concludes by discussing related works and directions for future work.

Change in modal parameters of cracked single-edge notched plain concrete Beams

[EN]The aim of this work is looking into the possibility of capturing the change in the modal properties (natural frequencies, modal shapes and modal damping ratio) of plain concrete elements due to the presence of cracked areas by using a simple continuum damage zone numerical model.