Contradictory reasoning network:an EEG and FMRI study

Contradiction is a cornerstone of human rationality, essential for everyday life and communication. We investigated electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) in separate recording sessions during contradictory judgments, using a logical structure based on categorical propositions of the Aristotelian Square of Opposition (ASoO). The use of ASoO propositions, while controlling for potential linguistic or semantic confounds, enabled us to observe the spatial temporal unfolding of this contradictory reasoning. The processing started with the inversion of the logical operators corresponding to right middle frontal gyrus (rMFG-BA11) activation, followed by identification of contradictory statement associated with in the right inferior frontal gyrus (rIFG-BA47) activation. Right medial frontal gyrus (rMeFG, BA10) and anterior cingulate cortex (ACC, BA32) contributed to the later stages of process. We observed a correlation between the delayed latency of rBA11 response and the reaction time delay during inductive vs. deductive reasoning. This supports the notion that rBA11 is crucial for manipulating the logical operators. Slower processing time and stronger brain responses for inductive logic suggested that examples are easier to process than general principles and are more likely to simplify communication. © 2014 Porcaro et al.

Antibacterial activity of 3-substituted pyrrole-2,5-diones against Pseudomonas aeruginosa

3-Substituted pyrrole-2,5-diones were synthesised from mucohalogen acids and the antibacterial activity was subsequently determined in biological assays. The minimum inhibitory concentration and the minimum bactericidal concentration of 2a were determined for a wide range of microorganisms in the low micromolar range. Protein identification using SDS-PAGE and LC/MS/MS demonstrated a partly degradation of OprF-related proteins giving an insight into the underlying mechanism of these novel antibacterial agents. © 2007 Bentham Science Publishers Ltd.

Novel 5-HT7 ligands as antidepressants:automated synthesis of N-substituted-N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]-arylsulfon amides

The 5-HT7 receptor is linked with various CNS disorders. Using an automated solution phase synthesis a combinatorial library of 384 N-substituted N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]-arylsulfonamides was prepared with 24 chemically diverse amines 1-24 and 16 sulfonyl chlorides A-P. The chemical library of alkylated sulfonamides was evaluated in a receptor binding assay with [3]H-5-CT as ligand. The key synthetic step was the alkylation of a sulfonamide with iodide E, which was prepared from butanediol in 4 synthetic steps. The target compounds 1A, 1B .....24A ... 24P were purified by solvent extraction on a Teacan liquid handling system. Sulfonamide J20, B23, D23, G23, G23, J23 , I24 and O24 displayed a binding affinity IC50 between 100 nM and 10 nM. The crystalline J20 (IC50=39 nM) and O24 (IC50=83 nM) were evaluated further in the despair swimming test and the tail suspension assay. A significant antidepressant activity was found in mice of a greater magnitude than imipramine and fluoxetine at low doses. © 2006 Bentham Science Publishers Ltd.

On the Models of Development and Distribution of Software

The notion model of development and distribution of software (MDDS) is introduced and its role for the efficiency of the software products is stressed. Two classical MDDS are presented and some attempts to adapt them to the contemporary trends in web-based software design are described. Advantages and shortcomings of the obtained models are outlined. In conclusion the desired features of a better MDDS for web-based solutions are given.

Visualisation of bioinformatics datasets

Analysing the molecular polymorphism and interactions of DNA, RNA and proteins is of fundamental importance in biology. Predicting functions of polymorphic molecules is important in order to design more effective medicines. Analysing major histocompatibility complex (MHC) polymorphism is important for mate choice, epitope-based vaccine design and transplantation rejection etc. Most of the existing exploratory approaches cannot analyse these datasets because of the large number of molecules with a high number of descriptors per molecule. This thesis develops novel methods for data projection in order to explore high dimensional biological dataset by visualising them in a low-dimensional space. With increasing dimensionality, some existing data visualisation methods such as generative topographic mapping (GTM) become computationally intractable. We propose variants of these methods, where we use log-transformations at certain steps of expectation maximisation (EM) based parameter learning process, to make them tractable for high-dimensional datasets. We demonstrate these proposed variants both for synthetic and electrostatic potential dataset of MHC class-I. We also propose to extend a latent trait model (LTM), suitable for visualising high dimensional discrete data, to simultaneously estimate feature saliency as an integrated part of the parameter learning process of a visualisation model. This LTM variant not only gives better visualisation by modifying the project map based on feature relevance, but also helps users to assess the significance of each feature. Another problem which is not addressed much in the literature is the visualisation of mixed-type data. We propose to combine GTM and LTM in a principled way where appropriate noise models are used for each type of data in order to visualise mixed-type data in a single plot. We call this model a generalised GTM (GGTM). We also propose to extend GGTM model to estimate feature saliencies while training a visualisation model and this is called GGTM with feature saliency (GGTM-FS). We demonstrate effectiveness of these proposed models both for synthetic and real datasets. We evaluate visualisation quality using quality metrics such as distance distortion measure and rank based measures: trustworthiness, continuity, mean relative rank errors with respect to data space and latent space. In cases where the labels are known we also use quality metrics of KL divergence and nearest neighbour classifications error in order to determine the separation between classes. We demonstrate the efficacy of these proposed models both for synthetic and real biological datasets with a main focus on the MHC class-I dataset.

On the Feasibility of Steering Swallowable Microsystem Capsules Using Computer-Aided Magnetic Levitation

Swallowable capsule endoscopy is used for non-invasive diagnosis of some gastrointestinal (GI) organs. However, control over the position of the capsule is a major unresolved issue. This study presents a design for steering the capsule based on magnetic levitation. The levitation is stabilized with the aid of a computer-aided feedback control system and diamagnetism. Peristaltic and gravitational forces to be overcome were calculated. A levitation setup was built to analyze the feasibility of using Hall Effect sensors to locate the in- vivo capsule. CAD software Maxwell 3D (Ansoft, Pittsburgh, PA) was used to determine the dimensions of the resistive electromagnets required for levitation and the feasibility of building them was examined. Comparison based on design complexity was made between positioning the patient supinely and upright.

The relative influence of social support, rehabilitation program participation, and inmate preincarceration characteristics on incarcerated substance abusers' perceptions of adjustment to community reintegration

This dissertation identifies, examines, and assesses the relative influence of identified empirically and conceptually relevant variables on incarcerated substance abusers' expectations of postrelease adjustment. A purposive sampling procedure was used to recruit 101 male and female substance-abusing offenders participating in prison- and jail-based drug treatment programs in south Florida. A 92-item survey questionnaire was used to collect basic demographic data; measure inmate preincarceration characteristics, social support, and rehabilitation program participation; and record archival data. Regression equations were developed utilizing ten different measures of the participants' expectations of their postrelease adjustment. Two equations yielded statistically significant F ratios; maintaining a stable living and maintaining abstinence. Twenty-two percent of the variance in respondents' expectations of maintaining a stable living was explained by preincarceration characteristics, social support, and rehabilitation program participation (F = 1.89; df = 13,87; p $<$.05). The only significant predictor variable was perception of social support (b = $-$.05; t = $-$3.6; p $<$.001). Twenty-three percent of the variance in respondents' expectations of maintaining abstinence from substances was explained by preincarceration characteristics, social support, and rehabilitation program participation (F = 2; df = 13,87; p $<$.05). Once again, the only significant predictor variable was perception of social support. The results of the analyses indicate that social support was the only important variable for understanding these respondents' efficacy expectations of postrelease abstinence and stable living. The results of this investigation demonstrate the complexity of the social support variable for prisoners, and identify social support as a potential rehabilitative resource for substance-abusing inmates. The results of this investigation underscore the importance of continued, detailed empirical study in order to understand and clarify how social support, efficacy expectations, and actual postrelease performance interrelate for this population of offenders.

Implementação em FPGA de módulo de efeito de reverberação

Reverberation is caused by the reflection of the sound in adjacent surfaces close to the sound source during its propagation to the listener. The impulsive response of an environment represents its reverberation characteristics. Being dependent on the environment, reverberation takes to the listener characteristics of the space where the sound is originated and its absence does not commonly sounds like “natural”. When recording sounds, it is not always possible to have the desirable characteristics of reverberation of an environment, therefore methods for artificial reverberation have been developed, always seeking a more efficient implementations and more faithful to the real environments. This work presents an implementation in FPGAs (Field Programmable Gate Arrays ) of a classic digital reverberation audio structure, based on a proposal of Manfred Schroeder, using sets of all-pass and comb filters. The developed system exploits the use of reconfigurable hardware as a platform development and implementation of digital audio effects, focusing on the modularity and reuse characteristics

Análise de superfícies seletivas em frequência com geometria multifractal

Frequency Selective surfaces are increasingly common structures in telecommunication systems due to their geometric and electromagnetic advantages. As a matter of fact, the frequency selective surfaces with fractal geometry type would allow an even bigger reduction of the electrical length which provided greater flexibility in the design of these structures. In this work, we investigated the use of multifractal geometry in frequency selective surfaces. Three structures with different multifractal geometries have been proposed and analyzed. The first structure allowed the design of multiband structures with greater flexibility in controlling the resonant frequencies and bandwidth. The second structure provided a bandwidth increase even with the rising of the fractal level. The third structure showed response with angle stability, dual polarization and provided room for a bandwidth increase with the rising of the structural multifractality. Furthermore, the proposed structures increased the degree of freedom in the multiband designs because they have multiple resonant frequencies ratios between adjacent bands and are easy to deploy. The validation of the proposed structures was initially verified through simulations in Ansoft Designer software and then the structures were constructed and the experimental results obtained

Ecologia de comunidades e comportamento reprodutivo de anfíbios anuros em savana amazônica

The Amazon savannas occur as isolated patches throughout extensive areas of forest in the states of Amapá, Amazonas, Pará, and Roraima. There is a considerable variation in the composition of anuran assemblages in the localities and phytophysiognomies of Amazon savannas and given the absence of studies on reproductive behavior, a systematic and geographically wide sampling has been carried out in the Amapá savanna, located in the Eastern Amazon. The study was conducted in a savanna area in the state of Amapá to examine the composition, ecology, and reproductive behavior of anuran amphibians. We carried out 24 field trips in each phytophysiognomy (gramineous-woody savana, gramineous-herbaceous-woody savana, park savana, and arboreal savanna); for analysis of reproductive behavior observations were made during the period January to December 2013, lasting four consecutive days. Samples were collected by active and acoustic search along 20 plots of 100x50 meters. Twenty-one anuran species were recorded, of which four are new records for the state of Amapá: Dendropsophus walfordi, Scinax fuscomarginatus, Pseudopaludicola boliviana e Elachistocleis helianneae. The KruskalWallis ANOVA revealed significant differences between richness and species diversity in the phytophysiognomies (p < 0.05). The Bray-Curtis similarity coefficient divided the phytophysiognomies into three groups: arboreal savana, gramineous-woody savanna and gramineous-herbaceous-woody savanna, and park savanna. According to the non-metric multidimensional scaling, the structure of the anuran community resulted in a separation into three phytophysiognomies, with significant differences in the structure of communities (ANOSIM, R = 0.823; p < 0.001). In the study of community ecology, the results obtained for spatial, temporal, and trophic niche breadth suggest that the assemblage of anurans of the Amapá savanna is not composed of predominantly generalist species. Also, the presence of other specialist anurans may explain the processes of speciation associated with the isolation of habitats, resulting in heterogeneity and spatial discontinuity in the phytophysiognomies with open formations. The null model analysis revealed that the community is structured based on temporal and trophic niche, indicating a significant influence of contemporary ecological factors on the assemblage. The absence of structure based on spatial niche might be explained by the spatial segregation in the distribution and occupation of anurans in the different phytophysiognomies of the Amapá savanna. Regarding the reproductive behavior of anurans, 11 species were classified as having a long breeding season, intrinsically associated with the rainy season and the reproductive mode of most species that lay egg clutches in lentic water bodies. Six reproductive modes were recorded and parental care was observed in Leptodactylus macrosternum and L. podicipinus, whose reproductive mode is characterized by foam nests. Regarding behavioral reproductive strategies, calling males were observed in all species of anurans, satellite males were recorded only for D. walfordi, Hypsiboas multifasciatus, S. nebulosus and S. fuscomarginatus; active search for females was observed for Phyllomedusa hypochondrialis and L. fuscus, and male displacement was recorded only for Rhinella major and R. margaritifera. Of the reproductive behaviors observed, throat and vocal sac display is associated with courtship and territorial behavior exhibited by males. In addition to courtship behavior, visual signals associated with courtship strategies were recorded for the anurans of the Amapá savanna.

Occurrence and Function of Hoogsteen Base Pairs in Nucleic Acids

Nucleic acids (DNA and RNA) play essential roles in the central dogma of biology for the storage and transfer of genetic information. The unique chemical and conformational structures of nucleic acids – the double helix composed of complementary Watson-Crick base pairs, provide the structural basis to carry out their biological functions. DNA double helix can dynamically accommodate Watson-Crick and Hoogsteen base-pairing, in which the purine base is flipped by ~180° degrees to adopt syn rather than anti conformation as in Watson-Crick base pairs. There is growing evidence that Hoogsteen base pairs play important roles in DNA replication, recognition, damage or mispair accommodation and repair. Here, we constructed a database for existing Hoogsteen base pairs in DNA duplexes by a structure-based survey from the Protein Data Bank, and structural analyses based on the resulted Hoogsteen structures revealed that Hoogsteen base pairs occur in a wide variety of biological contexts and can induce DNA kinking towards the major groove. As there were documented difficulties in modeling Hoogsteen or Watson-Crick by crystallography, we collaborated with the Richardsons’ lab and identified potential Hoogsteen base pairs that were mis-modeled as Watson-Crick base pairs which suggested that Hoogsteen can be more prevalent than it was thought to be. We developed solution NMR method combined with the site-specific isotope labeling to characterize the formation of, or conformational exchange with Hoogsteen base pairs in large DNA-protein complexes under solution conditions, in the absence of the crystal packing force. We showed that there are enhanced chemical exchange, potentially between Watson-Crick and Hoogsteen, at a sharp kink site in the complex formed by DNA and the Integration Host Factor protein. In stark contrast to B-form DNA, we found that Hoogsteen base pairs are strongly disfavored in A-form RNA duplex. Chemical modifications N1-methyl adenosine and N1-methyl guanosine that block Watson-Crick base-pairing, can be absorbed as Hoogsteen base pairs in DNA, but rather potently destabilized A-form RNA and caused helix melting. The intrinsic instability of Hoogsteen base pairs in A-form RNA endows the N1-methylation as a functioning post-transcriptional modification that was known to facilitate RNA folding, translation and potentially play roles in the epitranscriptome. On the other hand, the dynamic property of DNA that can accommodate Hoogsteen base pairs could be critical to maintaining the genome stability.

Current status of gene therapy for breast cancer: progress and challenges

Breast cancer is characterized by a series of genetic mutations and is therefore ideally placed for gene therapy intervention. The aim of gene therapy is to deliver a nucleic acid-based drug to either correct or destroy the cells harboring the genetic aberration. More recently, cancer gene therapy has evolved to also encompass delivery of RNA interference technologies, as well as cancer DNA vaccines. However, the bottleneck in creating such nucleic acid pharmaceuticals lies in the delivery. Deliverability of DNA is limited as it is prone to circulating nucleases; therefore, numerous strategies have been employed to aid with biological transport. This review will discuss some of the viral and nonviral approaches to breast cancer gene therapy, and present the findings of clinical trials of these therapies in breast cancer patients. Also detailed are some of the most recent developments in nonviral approaches to targeting in breast cancer gene therapy, including transcriptional control, and the development of recombinant, multifunctional bio-inspired systems. Lastly, DNA vaccines for breast cancer are documented, with comment on requirements for successful pharmaceutical product development.

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G₁ -S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1Amutant OCCC. Mol Cancer Ther; 15(7); 1472-84. Ó2016 AACR.

JCML: A specification language for the runtime verification of Java Card programs

COSTA, Umberto Souza; MOREIRA, Anamaria Martins; MUSICANTE, Matin A.; SOUZA NETO, Plácido A. JCML: A specification language for the runtime verification of Java Card programs. Science of Computer Programming. [S.l]: [s.n], 2010.