Hyperechoic breast lesions: anatomopathological correlation and differential sonographic diagnosis

Abstract Hyperechoic lesions are not a frequent finding at breasts ultrasonography, and most of times are associated with benign pathologies that do not require further evaluation. However, some neoplasms such as invasive breast carcinomas and metastases may present with hyperechogenicity. Thus, the knowledge about differential diagnoses and identification of signs of lesion aggressiveness are of great relevance to avoid unnecessary procedures or underdiagnosis, and to support the correct clinical/surgical approach. On the basis of such concepts, the present essay describes and illustrates the main features of hyperechoic lesions at breast ultrasonography in different cases, with anatomopathological correlation.

Paranoia and post-traumatic stress disorder in the months after a physical assault: a longitudinal study examining shared and differential predictors.

Background: Being physically assaulted is known to increase the risk of the occurrence of post-traumatic stress disorder (PTSD) symptoms but it may also skew judgements about the intentions of other people. The objectives of the study were to assess paranoia and PTSD after an assault and to test whether theory-derived cognitive factors predicted the persistence of these problems. Method: At 4 weeks after hospital attendance due to an assault, 106 people were assessed on multiple symptom measures (including virtual reality) and cognitive factors from models of paranoia and PTSD. The symptom measures were repeated 3 and 6 months later. Results: Factor analysis indicated that paranoia and PTSD were distinct experiences, though positively correlated. At 4 weeks, 33% of participants met diagnostic criteria for PTSD, falling to 16% at follow-up. Of the group at the first assessment, 80% reported that since the assault they were excessively fearful of other people, which over time fell to 66%. Almost all the cognitive factors (including information-processing style during the trauma, mental defeat, qualities of unwanted memories, self-blame, negative thoughts about self, worry, safety behaviours, anomalous internal experiences and cognitive inflexibility) predicted later paranoia and PTSD, but there was little evidence of differential prediction. Conclusions: Paranoia after an assault may be common and distinguishable from PTSD but predicted by a strikingly similar range of factors.

Conceptual Design of Embedded Weather Display

The objective of this thesis work is to describe the Conceptual Design process of an embedded electronic display device. The work presents the following sub processes: definition of device specifications, introduction to the technological alternatives for system components and their comparison, comparative photometric measurements of selected display panels, and the design and building of a functional concept prototype. This work focuses mainly on electronics design, albeit the mechanical issues and fields of the software architecture that significantly affect the decisions are also discussed when necessary. The VESA Flat Panel Display Measurement (FPDM) 2.0 Standard was applied to the appropriate extent into photometric measurements. The results were analyzed against the requirement standards of a customer-specific display development project. An Active Matrix LCD was selected as the display of concept prototype, but also the excellent visual characteristics of Active Matrix OLED technology were noted. Should the reliability of the OLED products be significantly improved in the future, utilizing such products in the described application must be reconsidered.

Interactions of bacteria and fungi on decomposing litter: differential extracellular enzyme activities

Fungi and bacteria are key agents in plant litter decomposition in freshwater ecosystems. However, the specific roles of these two groups and their interactions during the decomposition process are unclear. We compared the growth and patterns of degradativeenzymes expressed by communities of bacteria and fungi grown separately and in coexistence on Phragmites leaves. The two groups displayed both synergistic and antagonistic interactions. Bacteria grew better together with fungi than alone. In addition, there was a negative effect of bacteria on fungi, which appeared to be caused by suppression of fungal growth and biomass accrual rather than specifically affecting enzyme activity. Fungi growing alone had a high capacity for the decomposition of plant polymers such as lignin, cellulose, and hemicellulose. In contrast, enzyme activities were in general low when bacteria grew alone, and the activity of key enzymes in the degradation of lignin and cellulose (phenol oxidase and cellobiohydrolase) was undetectable in the bacteria-only treatment. Still, biomass-specific activities of most enzymes were higher in bacteria than in fungi. The low total activity and growth of bacteria in the absence of fungi in spite of apparent high enzymatic efficiency during the degradation of many substrates suggest that fungi provide the bacteria with resources that the bacteria were not able to acquire on their own, most probably intermediate decomposition products released by fungi that could be used by bacteria

Differential effects of two virtual reality interventions: distraction versus pain control

There is evidence that virtual reality (VR) pain distraction is effective at improving pain-related outcomes. However, more research is needed to investigate VR environments with other pain-related goals. The main aim of this study was to compare the differential effects of two VR environments on a set of pain-related and cognitive variables during a cold pressor experiment. One of these environments aimed to distract attention away from pain (VRD), whereas the other was designed to enhance pain control (VRC). Participants were 77 psychology students, who were randomly assigned to one of the following three conditions during the cold pressor experiment: (a) VRD, (b) VRC, or (c) Non-VR (control condition). Data were collected regarding both pain-related variables (intensity, tolerance, threshold, time perception, and pain sensitivity range) and cognitive variables (self-efficacy and catastrophizing). Results showed that in comparison with the control condition, the VRC intervention significantly increased pain tolerance, the pain sensitivity range, and the degree of time underestimation. It also increased self-efficacy in tolerating pain and led to a reduction in reported helplessness. The VRD intervention significantly increased the pain threshold and pain tolerance in comparison with the control condition, but it did not affect any of the cognitive variables. Overall, the intervention designed to enhance control seems to have a greater effect on the cognitive variables assessed. Although these results need to be replicated in further studies, the findings suggest that the VRC intervention has considerable potential in terms of increasing self-efficacy and modifying the negative thoughts that commonly accompany pain problems.

Differential Regulation of c-FLIP Isoforms Through Post-translational Modifications

Cells are constantly responding to signals from the surrounding tissues and the environment. To dispose of infected and potentially dangerous cells, to ensure the optimal execution of developmental processes and to maintain tissue homeostasis, a multicellular organism needs to tightly control both the number and the quality of its cells. Apoptosis is a form of active cellular self-destruction that enables an organism to regulate its cell number by deleting damaged or potentially dangerous cells. Apoptosis can be induced by death ligands, which bind to death receptors on the cell surface. Ligation of the receptors leads to the formation of an intracellular death inducing signaling complex (DISC). One of the DISC components is caspase-8, a protease that triggers the caspase cascade and is thereby a key initiator of programmed cell death. The activation of caspase-8 is controlled by the cellular FLICE-inhibitory proteins (c-FLIPs). Consequently, sensitivity towards receptor-mediated apoptosis is determined by the amount of c-FLIP, and the c-FLIP levels are actively regulated for example during erythroid differentiation of K562 erythroleukemia cells and by hyperthermia in Jurkat leukemia cells. The aim of my thesis was to investigate how c-FLIP is regulated during these processes. We found that c-FLIP isoforms are short-lived proteins, although c-FLIPS had an even shorter half-life than c-FLIPL. In both experimental models, increased death receptor sensitivity correlated with induced ubiquitylation and consequent proteasomal degradation of c-FLIP. Furthermore, we elucidated how phosphorylation regulates the biological functions and the turnover of c-FLIP, thereby contributing to death receptor sensitivity. We mapped the first phosphorylation sites on c-FLIP and dissected how their phosphorylation affects c-FLIP. Moreover, we demonstrated that phosphorylation of serine 193, a phosphorylated residue common to all c-FLIPs, is primarily mediated by the classical PKC. Furthermore, we discovered a novel connection between the phosphorylation and ubiquitylation of c-FLIP: phosphorylation of S193 protects c-FLIP from ubiquitylation. Surprisingly, although all c-FLIP isoforms are phosphorylated on this conserved residue, the biological outcome is different for the long and short isoforms, since S193 specifically prolongs the half-lives of the short c-FLIP isoforms, but not c-FLIPL. To summarize, we show that c-FLIP proteins are modified by ubiquitylation and phosphorylation, and that the biological outcomes of these modifications are isoform-specifically determined.

ContinuousMultimodal Global Optimization with Differential Evolution-Based Methods

Metaheuristic methods have become increasingly popular approaches in solving global optimization problems. From a practical viewpoint, it is often desirable to perform multimodal optimization which, enables the search of more than one optimal solution to the task at hand. Population-based metaheuristic methods offer a natural basis for multimodal optimization. The topic has received increasing interest especially in the evolutionary computation community. Several niching approaches have been suggested to allow multimodal optimization using evolutionary algorithms. Most global optimization approaches, including metaheuristics, contain global and local search phases. The requirement to locate several optima sets additional requirements for the design of algorithms to be effective in both respects in the context of multimodal optimization. In this thesis, several different multimodal optimization algorithms are studied in regard to how their implementation in the global and local search phases affect their performance in different problems. The study concentrates especially on variations of the Differential Evolution algorithm and their capabilities in multimodal optimization. To separate the global and local search search phases, three multimodal optimization algorithms are proposed, two of which hybridize the Differential Evolution with a local search method. As the theoretical background behind the operation of metaheuristics is not generally thoroughly understood, the research relies heavily on experimental studies in finding out the properties of different approaches. To achieve reliable experimental information, the experimental environment must be carefully chosen to contain appropriate and adequately varying problems. The available selection of multimodal test problems is, however, rather limited, and no general framework exists. As a part of this thesis, such a framework for generating tunable test functions for evaluating different methods of multimodal optimization experimentally is provided and used for testing the algorithms. The results demonstrate that an efficient local phase is essential for creating efficient multimodal optimization algorithms. Adding a suitable global phase has the potential to boost the performance significantly, but the weak local phase may invalidate the advantages gained from the global phase.

Differential responses of nematode communities to soybean genotypes resistant and susceptible to Heterodera glycines race 3

Heterodera glycines and Helicotylenchus dihystera were the two most abundant plant-parasitic nematodes found in two H. glycines race 3-infested fields, Chapadão do Céu, MS and Campo Alegre, MG. These fields had been planted with resistant (R) and susceptible (S) plants to cyst nematodes. In the first field, soybean (Glycine max) FT-Cristalina (S) was susceptible to H. glycines but resistant to H. dihystera, while GOBR93 122243 (R) was just the opposite. In the second field, M-Soy 8400 (R) was more resistant to the spiral nematode than M-Soy8411 (S), but the resistance to the cyst nematode was not different between the two genotypes. The total abundance of nematodes was not different between the susceptible and resistant plants in the two fields, suggesting that H. dihystera and/or bacterial feeders and other trophic groups replaced the reduced abundance of the cyst nematodes in resistant plants. Bacterial feeders acted as a compensatory factor to plant-parasitic nematodes in ecological function. The populations of fungal feeders were higher in GOBR93 122243 (R) than in susceptible FT-Cristalina (S) in Chapadão do Céu, but lower in M-Soy 8400 (R) than in M-Soy 8411 (S) in Campo Alegre. This is being attributed to the different periods of soil samplings that were made at the florescent period in the first field, and at the final growing cycle in the second field. Only four nematodes, H. glycines, H. dihystera, Acrobeles sp. and Panagrolaimus sp. dominated the nematode resistant community GOBR93 122243 (R) in Chapadão do Céu, but dominance was shared by ten genera in Campo Alegre, which explains why the five diversity indexes (S, d, Ds, H' and T) were higher in resistant plants than in susceptible plants in field two.

Evolution of Bioaffinity Reagents by Phage Display

Antibodies are natural binding proteins produced in vertebrates as a response to invading pathogens and foreign substances. Because of their capability for tight and specific binding, antibodies have found use as binding reagents in research and diagnostics. Properties of cloned recombinant antibodies can be further improved by means of in vitro evolution, combining mutagenesis with subsequent phage display selection. It is also possible to isolate entirely new antibodies from vast naïve or synthetic antibody libraries by phage display. In this study, library techniques and phage display selection were applied in order to optimise binding scaffolds and antigen recognition of antibodies, and to evolve new and improved bioaffinity reagents. Antibody libraries were generated by random and targeted mutagenesis. Expression and stability were mainly optimised by the random methods whereas targeted randomisation of the binding site residues was used for optimising the binding properties. Trinucleotide mutagenesis allowed design of defined randomisation patterns for a synthetic antibody library. Improved clones were selected by phage display. Capture by a specific anti- DHPS antibody was exploited in the selection of improved phage display of DHPS. Efficient selection for stability was established by combining phage display selection with denaturation under reducing conditions. Broad-specific binding of a generic anti-sulfonamide antibody was improved by selection with one of the weakest binding sulfonamides. In addition, p9 based phage display was studied in affinity selection from the synthetic library. A TIM barrel protein DHPS was engineered for efficient phage display by combining cysteinereplacement with random mutagenesis. The resulting clone allows use of phage display in further engineering of DHPS and possibly use as an alternative-binding scaffold. An anti-TSH scFv fragment, cloned from a monoclonal antibody, was engineered for improved stability to better suite an immunoassay. The improved scFv tolerates 8 – 9 °C higher temperature than the parental scFv and should have sufficient stability to be used in an immunoanalyser with incubation at 36 °C. The anti-TSH scFv fragment was compared with the corresponding Fab fragment and the parental monoclonal antibody as a capturing reagent in a rapid 5-min immunoassay for TSH. The scFv fragment provided some benefits over the conventionally used Mab in anayte-binding capacity and assay kinetics. However, the recombinant Fab fragment, which had similar kinetics to the scFv, provided a more sensitive and reliable assay than the scFv. Another cloned scFv fragment was engineered in order to improve broad-specific recognition of sulfonamides. The improved antibody detects different sulfonamides at concentrations below the maximum residue limit (100 μg/kg in EU and USA) and allows simultaneous screening of different sulfonamide drug residues. Finally, a synthetic antibody library was constructed and new antibodies were generated and affinity matured entirely in vitro. These results illuminate the possibilities of phage display and antibody engineering for generation and optimisation of binding reagents in vitro and indicate the potential of recombinant antibodies as affinity reagents in immunoassays.

Application of differential scanning calorimetry in hair samples as a possible tool in Forensic Science

The Differential Scanning Calorimetry (DSC) was used to study the thermal behavior of hair samples and to verify the possibility of identifying an individual based on DSC curves from a data bank. Hair samples of students and officials from Instituto de Química de Araraquara, UNESP were obtained to build up a data bank. Thus to sought an individual, under incognito participant of this data bank, was identified using DSC curves.

Reaction of wheat cultivars and differential lines to Puccinia triticina races in detached leaves

The method of preserving detached wheat leaves in Petri dish was used for the inoculation and development of the fungus Puccinia triticina, the causal agent of wheat leaf rust. The reaction of 26 wheat cultivars was compared by using seedlings cultivated in pots (in vivo) and detached leaves (in vitro) inoculated with four physiological races of the pathogen. After inoculation, the material was kept in a growth chamber for 15 days. The reaction was evaluated on the 15th day after inoculation. Results for each race in the evaluated genotypes confirmed the efficiency of the detached leaf method in assessing the reaction of wheat cultivars.

DIFFERENTIAL RESPONSE OF CLONES OF EUCALYPT TO GLYPHOSATE1

Weed control is commonly performed by the inter-row mechanical weeding associated to intrarow glyphosate directed spraying, causing a risk for drift or accidental herbicide application, that can affect the crop of interest. The objective was to evaluate the response of clones C219, GG100, I144, and I224 of eucalypt (Eucalyptus grandis x E. urophylla) to glyphosate doses of 0, 18, 36, 72, 180, 360, and 720 g of acid equivalent per hectare. The clones showed different growth patterns with regard to height, leaf number, stem dry weight, relative growth rate, net assimilation rate, and relative leaf growth rate. The clones I144 and GG100 were more susceptible to glyphosate, showing the doses required to reduce dry weight by 50% of 113.4 and 119.6 g acid equivalent per hectare, respectively. The clones C219 and I224 were less susceptible to glyphosate, showing the doses required to reduce dry weight by 50% of 237.5 and 313.5 g acid equivalent per hectare, respectively. Eucalyptus clones respond differently to glyphosate exposure, so that among I224, C219, GG100, and I144, the susceptibility to the herbicide is increasing.

Generalized Differential Evolution for Global Multi-Objective Optimization with Constraints

The objective of this thesis work is to develop and study the Differential Evolution Algorithm for multi-objective optimization with constraints. Differential Evolution is an evolutionary algorithm that has gained in popularity because of its simplicity and good observed performance. Multi-objective evolutionary algorithms have become popular since they are able to produce a set of compromise solutions during the search process to approximate the Pareto-optimal front. The starting point for this thesis was an idea how Differential Evolution, with simple changes, could be extended for optimization with multiple constraints and objectives. This approach is implemented, experimentally studied, and further developed in the work. Development and study concentrates on the multi-objective optimization aspect. The main outcomes of the work are versions of a method called Generalized Differential Evolution. The versions aim to improve the performance of the method in multi-objective optimization. A diversity preservation technique that is effective and efficient compared to previous diversity preservation techniques is developed. The thesis also studies the influence of control parameters of Differential Evolution in multi-objective optimization. Proposals for initial control parameter value selection are given. Overall, the work contributes to the diversity preservation of solutions in multi-objective optimization.

Ion selective electrodes for determination of low and ultra low concentrations of lead (II) in natural waters

Att övervaka förekomsten av giftiga komponenter i naturliga vattendrag är nödvändigt för människans välmående. Eftersom halten av föroreningar i naturens ekosystem bör hållas möjligast låg, pågår en ständig jakt efter kemiska analysmetoder med allt lägre detektionsgränser. I dagens läge görs miljöanalyser med dyr och sofistikerad instrumentering som kräver mycket underhåll. Jonselektiva elektroder har flera goda egenskaper som t.ex. bärbarhet, låg energiförbrukning, och dessutom är de relativt kostnadseffektiva. Att använda jonselektiva elektroder vid miljöanalyser är möjligt om deras känslighetsområde kan utvidgas genom att sänka deras detektionsgränser. För att sänka detektionsgränsen för Pb(II)-selektiva elektroder undersöktes olika typer av jonselektiva membran som baserades på polyakrylat-kopolymerer, PVC och PbS/Ag2S. Fast-fas elektroder med membran av PbS/Ag2S är i allmänhet enklare och mer robusta än konventionella elektroder vid spårämnesanalys av joniska föroreningar. Fast-fas elektrodernas detektionsgräns sänktes i detta arbete med en nyutvecklad galvanostatisk polariseringsmetod och de kunde sedan framgångsrikt användas för kvantitativa bestämningar av bly(II)-halter i miljöprov som hade samlats in i den finska skärgården nära tidigare industriområden. Analysresultaten som erhölls med jonselektiva elektroder bekräftades med andra analytiska metoder. Att sänka detektionsgränsen m.hj.a. den nyutvecklade polariseringsmetoden möjliggör bestämning av låga och ultra-låga blyhalter som inte kunde nås med klassisk potentiometri. Den verkliga fördelen med att använda dessa blyselektiva elektroder är möjligheten att utföra mätningar i obehandlade miljöprov trots närvaron av fasta partiklar vilket inte är möjligt att göra med andra analysmetoder. Jag väntar mig att den nyutvecklade polariseringsmetoden kommer att sätta en trend i spårämnesanalys med jonselektiva elektroder.