Memristive Computing

Memristive computing refers to the utilization of the memristor, the fourth fundamental passive circuit element, in computational tasks. The existence of the memristor was theoretically predicted in 1971 by Leon O. Chua, but experimentally validated only in 2008 by HP Labs. A memristor is essentially a nonvolatile nanoscale programmable resistor — indeed, memory resistor — whose resistance, or memristance to be precise, is changed by applying a voltage across, or current through, the device. Memristive computing is a new area of research, and many of its fundamental questions still remain open. For example, it is yet unclear which applications would benefit the most from the inherent nonlinear dynamics of memristors. In any case, these dynamics should be exploited to allow memristors to perform computation in a natural way instead of attempting to emulate existing technologies such as CMOS logic. Examples of such methods of computation presented in this thesis are memristive stateful logic operations, memristive multiplication based on the translinear principle, and the exploitation of nonlinear dynamics to construct chaotic memristive circuits. This thesis considers memristive computing at various levels of abstraction. The first part of the thesis analyses the physical properties and the current-voltage behaviour of a single device. The middle part presents memristor programming methods, and describes microcircuits for logic and analog operations. The final chapters discuss memristive computing in largescale applications. In particular, cellular neural networks, and associative memory architectures are proposed as applications that significantly benefit from memristive implementation. The work presents several new results on memristor modeling and programming, memristive logic, analog arithmetic operations on memristors, and applications of memristors. The main conclusion of this thesis is that memristive computing will be advantageous in large-scale, highly parallel mixed-mode processing architectures. This can be justified by the following two arguments. First, since processing can be performed directly within memristive memory architectures, the required circuitry, processing time, and possibly also power consumption can be reduced compared to a conventional CMOS implementation. Second, intrachip communication can be naturally implemented by a memristive crossbar structure.

Sirolimus influence on hepatectomy-induced liver regeneration in rats

OBJECTIVE: To evaluate the influence of sirolimus on liver regeneration triggered by resection of 70% of the liver of adult rats.METHODS: we used 40 Wistar rats randomly divided into two groups (study and control), each group was divided into two equal subgroups according to the day of death (24 hours and seven days). Sirolimus was administered at a dose of 1mg/kg in the study group and the control group was given 1 ml of saline. The solutions were administered daily since three days before hepatectomy till the rats death to removal of the regenerated liver, conducted in 24 hours or 7 days after hepatectomy. Liver regeneration was measured by the KWON formula, by thenumber of mitotic figures (hematoxylin-eosin staining) and by the immunohistochemical markers PCNA and Ki-67.RESULTS: there was a statistically significant difference between the 24h and the 7d groups. When comparing the study and control groups in the same period, there was a statistically significant variation only for Ki-67, in which there were increased numbers of hepatocytes in cell multiplication in the 7d study group compared with the 7d control group (p = 0.04).CONCLUSION: there was no negative influence of sirolimus in liver regeneration and there was a positive partial effect at immunohistochemistry with Ki-67.

Hofbauer cells morphology and density in placentas from normal and pathological gestations

PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens.

The role of ear mites of the genus Raillietia (Acari: Raillietiidae) in otitis of domestic ruminants

This paper presents a hypothesis on the involvement of species of the genus Raillietia Trouessart in the pathology of parasitic otitis in domestic ruminants. The chelicerae and claws of the tarsi are structures that contribute significantly towards producing primary lesions. The movable digits of the chelicerae accidentally injure the epithelium that lines the ear canal, while the claws of the tarsi perforate the epithelium, allowing the mites to affix themselves while feeding. The lesions in the epithelium caused by the chelicerae and the claws favor multiplication of the bacteria that inhabit the ear canal, resulting in typical cases of otitis.

Influência de fontes de nitrogênio sobre o desenvolvimento das gemas axilares de explantes caulinares de Chrysanthemum morifolium Ramat. cultivado in vitro

Foram testadas diferentes fontes de nitrogênio na indução e enraizamento de brotações axilares de Chrysanthemum morifolium. Manteve-se constante o teor de nitrogênio total (60 mM) em todos os tratamentos realizados, variando-se apenas as fontes nitrogenadas. O tratamento E1 constituiu-se do meio MS (Murashige & Skoog 1962) completo. Os demais tratamentos foram: E2 = amônio; E3 = nitrato; E4 = nitrato+uréia (1,65 mM); E5 = nitrato+uréia (3,33 mM); E6 = uréia; E7 = uréia+glutamina e E8 = glutamina. Em nenhum tratamento foram adicionados fitorreguladores. No tratamento E1 houve um favorecimento de desenvolvimento de plantas de crisântemo in vitro tanto da parte aérea como de raízes. Porém, a utilização apenas de nitrato como única fonte de nitrogênio (tratamento E3) foi suficiente para sustentar o desenvolvimento das plantas, pois, para a maioria dos parâmetros analisados não foi observada diferença significativa em relação às plantas mantidas no meio básico de MS. A presença de uréia no meio de cultura incrementou o desenvolvimento de raízes de crisântemo, principalmente quando utilizada em adição ao nitrato (tratamentos E4 e E5), proporcionando um sistema radicular bastante denso. Quando utilizadas como única fonte de nitrogênio, tanto a glutamina (tratamento E7) como o íon amônio (tratamento E2) não se mostraram eficientes. O resultado do uso das fontes mencionadas foi um baixo desenvolvimento das plantas, como evidenciado pelos baixos valores de crescimento obtidos em todos os parâmetros analisados.

In vitro culture of Phyllanthus stipulatus (Euphorbiaceae)

An efficient micropropagation protocol was developed for the medicinal plant Phyllanthus stipulatus (Euphorbiaceae) using nodal segments for axillary shoot proliferation. Maximum multiplication rates (8-9 shoots per explant) was achieved on MS media supplemented with either 2.5-5.0 muM IBA. The best basal media for axillary shoot proliferation when 0.62 muM BA was supplemented were MS, MS/2 and AR (4-5 shoots per explant). Rooting was achieved with 100% of the microshoots on MS medium without growth regulators. Regenerated plants were successfully acclimatized and about 88% of plantlets survived under ex vitro conditions. Flowering was observed in 81% of the ex vitro grown plantlets after 12 weeks of acclimatization. High frequency callus initiation and growth was achieved when nodal segment explants were inoculated either in the vertical position, in the light on MS medium supplemented with 5.0 muM NAA or horizontally oriented, in the dark on MS supplemented with 5.0 muM NAA or 1.25-5.0 muM BA or 2iP. Root cultures were successfully established on MS medium containing 1.1 muM NAA. The optimized micropropagation, callus and root culture protocols offer the possibility to use cell/organ culture techniques for vegetative propagation and secondary metabolism studies.

Changes in polyamines content associated with zygotic embryogenesis in the Brazilian pine, Araucaria angustifolia (Bert.) O. Ktze.

Changes in the polyamine content were analyzed in different embryo developmental stages and tissues during seed development in the conifer Araucaria angustifolia (Bert.) O. Ktze. Free polyamine contents varied according to the tissue and stage of embryo development, the highest levels occurring in the embryonic axis at the early stages, when putrescine and spermidine were most abundant. The levels of spermidine were higher from the stage where cotyledons arise, whereas putrescine decreases. The putrescine/spermine+spermidine ratio was higher during the initial phases of seed development, corresponding to cell multiplication and elongation, with a decrease in the final stages, corresponding to stabilization of the dry matter content.

Mixed reproduction systems in Opuntia monacantha (Cactaceae) in Southern Brazil

The Cactaceae have morphological and physiological adaptations associated with their life histories that are reflected in different modes of reproduction and multiplication. The reproductive phenology, preferential reproductive mode, and the sexual and asexual multiplication of Opuntia monacantha were investigated between 2003 and 2006 in two restinga (sandy coastal) environment in Southern Brazil to determine the adaptive values of its reproduction modes. Flowering was annual and occurred continuous for approximately 100 days between the months of September and January, with a few flowers opening per day per individual (but many in the whole population). Facultative xenogamy was identified as the preferential sexual system, with the highest levels of fruit and seed formation following natural pollination. The seeds are recalcitrant and have high germinative capacities under laboratory conditions. Seedling recruitment and establishment in the field was extremely reduced. The skins of the fruits and the cladodes have high capacities for regeneration and clonal multiplication because of their areolas.

Conflicting genomes, the demic theory & biodiversity

Organismic-centered Darwinism, in order to use direct phenotypes to measure natural selection's effect, necessitates genome's harmony and uniform coherence plus large population sizes. However, modern gene-centered Darwinism has found new interpretations to data that speak of genomic incoherence and disharmony. As a result of these two conflicting positions a conceptual crisis in Biology has arisen. My position is that the presence of small, even pocket-size, demes is instrumental in generating divergence and phenotypic crisis. Moreover, the presence of parasitic genomes as in acanthocephalan worms, which even manipulate suicidal behavior in their hosts; segregation distorters that change meiosis and Mendelian ratios; selfish genes and selfish whole chromosomes, such as the case of B-chromosomes in grasshoppers; P-elements in Drosophila; driving Y-chromosomes that manipulate sex ratios making males more frequent, as in Hamilton's X-linked drive; male strategists and outlaw genes, are eloquent examples of the presence of real conflicting genomes and of a non-uniform phenotypic coherence and genome harmony. Thus, we are proposing that overall incoherence and disharmony generate disorder but also more biodiversity and creativeness. Finally, if genes can manipulate natural selection, they can multiply mutations or undesirable characteristics and even lethal or detrimental ones, hence the accumulation of genetic loads. Outlaw genes can change what is adaptively convenient even in the direction of the trait that is away from the optimum. The optimum can be "negotiated" among the variants, not only because pleiotropic effects demand it, but also, in some cases, because selfish, outlaw, P-elements or extended phenotypic manipulation require it. With organismic Darwinism the genome in the population and in the individual was thought to act harmoniously without conflicts, and genotypes were thought to march towards greater adaptability. Modern Darwinism has a gene-centered vision in which genes, as natural selection's objects can move in dissonance in the direction which benefits their multiplication. Thus, we have greater opportunities for genomes in permanent conflict.

Induction of cell-mediated immunity during early stages of infection with intracellular protozoa

Toxoplasma gondii and Trypanosoma cruzi are intracellular parasites which, as part of their life cycle, induce a potent cell-mediated immunity (CMI) maintained by Th1 lymphocytes and IFN-g. In both cases, induction of a strong CMI is thought to protect the host against rapid parasite multiplication and consequent pathology and lethality during the acute phase of infection. However, the parasitic infection is not eliminated by the immune system and the vertebrate host serves as a parasite reservoir. In contrast, Leishmania sp, which is a slow growing parasite, appears to evade induction of CMI during early stages of infection as a strategy for surviving in a hostile environment (i.e., inside the macrophages which are their obligatory niche in the vertebrate host). Recent reports show that the initiation of IL-12 synthesis by macrophages during these parasitic infections is a key event in regulating CMI and disease outcome. The studies reviewed here indicate that activation/inhibition of distinct signaling pathways and certain macrophage functions by intracellular protozoa are important events in inducing/modulating the immune response of their vertebrate hosts, allowing parasite and host survival and therefore maintaining parasite life cycles.

Cytokine profile and pathology in human leishmaniasis

The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-g is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-g production and high IL-4 and IL-10 levels (Th2 cytokines) are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC). Moreover, IL-12 restores IFN-g production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-g production, since anti-IL-10 monoclonal antibody (mAb) restores in vitro IFN-g production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-g are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-g levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 ± 26 pg/ml). This response was restored by IL-12 (308 ± 342 pg/ml) and anti-IL-10 mAb (380 ± 245 pg/ml) (P<0.05). Later during the disease, high levels of IFN-g and TNF-a are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-a levels (366 ± 224 pg/ml before treatment vs 142 ± 107 pg/ml after treatment, P = 0.02). Although production of IFN-g and TNF-a might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis

A single strain of Mycobacterium bovis bacillus Calmette-Guérin (BCG) grown in two different media evokes distinct humoral immune responses in mice

Two attenuated bacillus Calmette-Guérin (BCG) preparations derived from the same Moreau strain, Copenhagen but grown in Sauton medium containing starch and bacto-peptone (onco BCG, O-BCG), or asparagine (intradermal BCG, ID-BCG), exhibited indistinguishable DNA sequences and bacterial morphology. The number of viable bacilli recovered from spleen, liver and lungs was approximately the same in mice inoculated with the vaccines and was similarly reduced (over 90%) in mice previously immunized with either BCG vaccine. The humoral immune response evoked by the vaccines was, however, distinct. Spleen cell proliferation accompanying the growth of bacilli in tissue was significantly higher in mice inoculated with O-BCG. These cells proliferated in vitro upon challenge with the corresponding BCG extract. Previous cell treatment with mAb anti-CD4 T cells abolished this effect. Anti-BCG antibodies, as assayed either in serum by ELISA or by determining the number of antibody-producing spleen cells by the spot-ELISA method, were significantly higher in mice inoculated with ID-BCG. Anti-BCG antibodies were detected in all immunoglobulin classes, but they were more prevalent in IgG with the following distribution among its isotypes: IgG1>(IgG2a = IgG2b)>IgG3. When some well-characterized Mycobacterium tuberculosis antigens were used as substitutes for BCG extracts in ELISA, although antibodies against the 65-kDa and 96-kDa proteins were detected significantly, antibodies against the 71-kDa, 38-kDa proteins and lipoarabinomannan were only barely detected or even absent. These results indicate that BCG bacilli cultured in Sauton-asparagine medium permitted the multiplication of bacilli, tending to induce a stronger humoral immune response as compared with bacilli grown in Sauton-starch/bacto-peptone-enriched medium.

Mathematical modeling and optimal control of malaria

Malaria continues to infect millions and kill hundreds of thousands of people worldwide each year, despite over a century of research and attempts to control and eliminate this infectious disease. Challenges such as the development and spread of drug resistant malaria parasites, insecticide resistance to mosquitoes, climate change, the presence of individuals with subpatent malaria infections which normally are asymptomatic and behavioral plasticity in the mosquito hinder the prospects of malaria control and elimination. In this thesis, mathematical models of malaria transmission and control that address the role of drug resistance, immunity, iron supplementation and anemia, immigration and visitation, and the presence of asymptomatic carriers in malaria transmission are developed. A within-host mathematical model of severe Plasmodium falciparum malaria is also developed. First, a deterministic mathematical model for transmission of antimalarial drug resistance parasites with superinfection is developed and analyzed. The possibility of increase in the risk of superinfection due to iron supplementation and fortification in malaria endemic areas is discussed. The model results calls upon stakeholders to weigh the pros and cons of iron supplementation to individuals living in malaria endemic regions. Second, a deterministic model of transmission of drug resistant malaria parasites, including the inflow of infective immigrants, is presented and analyzed. The optimal control theory is applied to this model to study the impact of various malaria and vector control strategies, such as screening of immigrants, treatment of drug-sensitive infections, treatment of drug-resistant infections, and the use of insecticide-treated bed nets and indoor spraying of mosquitoes. The results of the model emphasize the importance of using a combination of all four controls tools for effective malaria intervention. Next, a two-age-class mathematical model for malaria transmission with asymptomatic carriers is developed and analyzed. In development of this model, four possible control measures are analyzed: the use of long-lasting treated mosquito nets, indoor residual spraying, screening and treatment of symptomatic, and screening and treatment of asymptomatic individuals. The numerical results show that a disease-free equilibrium can be attained if all four control measures are used. A common pitfall for most epidemiological models is the absence of real data; model-based conclusions have to be drawn based on uncertain parameter values. In this thesis, an approach to study the robustness of optimal control solutions under such parameter uncertainty is presented. Numerical analysis of the optimal control problem in the presence of parameter uncertainty demonstrate the robustness of the optimal control approach that: when a comprehensive control strategy is used the main conclusions of the optimal control remain unchanged, even if inevitable variability remains in the control profiles. The results provide a promising framework for the design of cost-effective strategies for disease control with multiple interventions, even under considerable uncertainty of model parameters. Finally, a separate work modeling the within-host Plasmodium falciparum infection in humans is presented. The developed model allows re-infection of already-infected red blood cells. The model hypothesizes that in severe malaria due to parasite quest for survival and rapid multiplication, the Plasmodium falciparum can be absorbed in the already-infected red blood cells which accelerates the rupture rate and consequently cause anemia. Analysis of the model and parameter identifiability using Markov chain Monte Carlo methods is presented.

Development of an HTR-10 model in the Serpent reactor physics code

The use of exact coordinates of pebbles and fuel particles of pebble bed reactor modelling becoming possible in Monte Carlo reactor physics calculations is an important development step. This allows exact modelling of pebble bed reactors with realistic pebble beds without the placing of pebbles in regular lattices. In this study the multiplication coefficient of the HTR-10 pebble bed reactor is calculated with the Serpent reactor physics code and, using this multiplication coefficient, the amount of pebbles required for the critical load of the reactor. The multiplication coefficient is calculated using pebble beds produced with the discrete element method and three different material libraries in order to compare the results. The received results are lower than those from measured at the experimental reactor and somewhat lower than those gained with other codes in earlier studies.

Neuropsychological rehabilitation of memory deficits and activities of daily living in patients with Alzheimer's disease: a pilot study

Patients with Alzheimer's disease (AD) gradually lose their cognitive competence, particularly memory, and the ability to perform daily life tasks. Neuropsychological rehabilitation is used to improve cognitive functions by facilitating memory performance through the use of external aids and internal strategies. The effect of neuropsychological rehabilitation through memory training - motor movements, verbal association, and categorization - and activities of daily living (ADL) training was tested in a sample of 5 elderly out-patients (mean age: 77.4 ± 2.88 years), with mild AD (Mini-Mental State Examination score: 22.20 ± 2.17) and their caregivers. All patients had been taking rivastigmine (6-12 mg/day) for at least 3 months before being assigned to the rehabilitation sessions, and they continued to take the medication during the whole program. Just before and after the 14-week neuropsychological rehabilitation program all patients were assessed by interviewers that did not participate in the cognitive training, using the Mini-Mental State Examination, Montgomery-Alsberg Depression Rating Scale, Hamilton Anxiety Scale, Interview to Determine Deterioration in Functioning in Dementia, Functional Test, Memory Questionnaire of Daily Living for patient and caregiver, Quality of Life Questionnaire for patient and caregiver, and a neuropsychological battery. The results showed a statistically significant improvement in ADL measured by Functional Test (P = 0.04), and only a small improvement in memory and psychiatric symptoms. Our results support the view that weekly stimulation of memory and training of ADL is believed to be of great value in AD treatment, not only delaying the progress of the disease, but also improving some cognitive functions and ADL, even though AD is a progressively degenerative disease.