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.

Specification and Runtime Verification of Java Card Programs

COSTA, Umberto Souza da; MOREIRA, Anamaria Martins; MUSICANTE, Martin A. Specification and Runtime Verification of Java Card Programs. Electronic Notes in Theoretical Computer Science. [S.l:s.n], 2009.

Loess as a Collapsible Soil: Some Basic Particle Packing

Loess is the most important collapsible soil; possibly the only engineering soil in which real collapse occurs. A real collapse involves a diminution in volume - it would be an open metastable packing being reduced to a more closely packed, more stable structure. Metastability is at the heart of the collapsible soils problem. To envisage and to model the collapse process in a metastable medium, knowledge is required about the nature and shape of the particles, the types of packings they assume (real and ideal), and the nature of the collapse process - a packing transition upon a change to the effective stress in a media of double porosity. Particle packing science has made little progress in geoscience discipline - since the initial packing paradigms set by Graton and Fraser (1935) - nevertheless is relatively well-established in the soft matter physics discipline. The collapse process can be represented by mathematical modelling of packing – including the Monte Carlo simulations - but relating representation to process remains difficult. This paper revisits the problem of sudden packing transition from a micro-physico-mechanical viewpoint (i.e. collapse imetan terms of structure-based effective stress). This cross-disciplinary approach helps in generalization on collapsible soils to be made that suggests loess is the only truly collapsible soil, because it is only loess which is so totally influenced by the packing essence of the formation process.

Security through Obscurity: Layout Obfuscation of Digital Integrated Circuits using Don't Care Conditions

Contemporary integrated circuits are designed and manufactured in a globalized environment leading to concerns of piracy, overproduction and counterfeiting. One class of techniques to combat these threats is circuit obfuscation which seeks to modify the gate-level (or structural) description of a circuit without affecting its functionality in order to increase the complexity and cost of reverse engineering. Most of the existing circuit obfuscation methods are based on the insertion of additional logic (called “key gates”) or camouflaging existing gates in order to make it difficult for a malicious user to get the complete layout information without extensive computations to determine key-gate values. However, when the netlist or the circuit layout, although camouflaged, is available to the attacker, he/she can use advanced logic analysis and circuit simulation tools and Boolean SAT solvers to reveal the unknown gate-level information without exhaustively trying all the input vectors, thus bringing down the complexity of reverse engineering. To counter this problem, some ‘provably secure’ logic encryption algorithms that emphasize methodical selection of camouflaged gates have been proposed previously in literature [1,2,3]. The contribution of this paper is the creation and simulation of a new layout obfuscation method that uses don't care conditions. We also present proof-of-concept of a new functional or logic obfuscation technique that not only conceals, but modifies the circuit functionality in addition to the gate-level description, and can be implemented automatically during the design process. Our layout obfuscation technique utilizes don’t care conditions (namely, Observability and Satisfiability Don’t Cares) inherent in the circuit to camouflage selected gates and modify sub-circuit functionality while meeting the overall circuit specification. Here, camouflaging or obfuscating a gate means replacing the candidate gate by a 4X1 Multiplexer which can be configured to perform all possible 2-input/ 1-output functions as proposed by Bao et al. [4]. It is important to emphasize that our approach not only obfuscates but alters sub-circuit level functionality in an attempt to make IP piracy difficult. The choice of gates to obfuscate determines the effort required to reverse engineer or brute force the design. As such, we propose a method of camouflaged gate selection based on the intersection of output logic cones. By choosing these candidate gates methodically, the complexity of reverse engineering can be made exponential, thus making it computationally very expensive to determine the true circuit functionality. We propose several heuristic algorithms to maximize the RE complexity based on don’t care based obfuscation and methodical gate selection. Thus, the goal of protecting the design IP from malicious end-users is achieved. It also makes it significantly harder for rogue elements in the supply chain to use, copy or replicate the same design with a different logic. We analyze the reverse engineering complexity by applying our obfuscation algorithm on ISCAS-85 benchmarks. Our experimental results indicate that significant reverse engineering complexity can be achieved at minimal design overhead (average area overhead for the proposed layout obfuscation methods is 5.51% and average delay overhead is about 7.732%). We discuss the strengths and limitations of our approach and suggest directions that may lead to improved logic encryption algorithms in the future. References: [1] R. Chakraborty and S. Bhunia, “HARPOON: An Obfuscation-Based SoC Design Methodology for Hardware Protection,” IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems, vol. 28, no. 10, pp. 1493–1502, 2009. [2] J. A. Roy, F. Koushanfar, and I. L. Markov, “EPIC: Ending Piracy of Integrated Circuits,” in 2008 Design, Automation and Test in Europe, 2008, pp. 1069–1074. [3] J. Rajendran, M. Sam, O. Sinanoglu, and R. Karri, “Security Analysis of Integrated Circuit Camouflaging,” ACM Conference on Computer Communications and Security, 2013. [4] Bao Liu, Wang, B., "Embedded reconfigurable logic for ASIC design obfuscation against supply chain attacks,"Design, Automation and Test in Europe Conference and Exhibition (DATE), 2014 , vol., no., pp.1,6, 24-28 March 2014.

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.

Specification and Runtime Verification of Java Card Programs

COSTA, Umberto Souza da; MOREIRA, Anamaria Martins; MUSICANTE, Martin A. Specification and Runtime Verification of Java Card Programs. Electronic Notes in Theoretical Computer Science. [S.l:s.n], 2009.

High diversity of skin-associated bacterial communities of marine fishes is promoted by their high variability among body parts, individuals and species

Animal-associated microbiotas form complex communities, which are suspected to play crucial functions for their host fitness. However, the biodiversity of these communities, including their differences between host species and individuals, has been scarcely studied, especially in case of skin-associated communities. In addition, the intraindividual variability (i.e. between body parts) has never been assessed to date. The objective of this study was to characterize skin bacterial communities of two teleostean fish species, namely the European seabass (Dicentrarchus labrax) and gilthead seabream (Sparus aurata), using a high-throughput DNA sequencing method. In order to focus on intrinsic factors of host-associated bacterial community variability, individuals of the two species were raised in controlled conditions. Bacterial diversity was assessed using a set of four complementary indices, describing the taxonomic and phylogenetic facets of biodiversity and their respective composition (based on presence/absence data) and structure (based on species relative abundances) components. Variability of bacterial diversity was quantified at the interspecific, interindividual and intraindividual scales. We demonstrated that fish surfaces host highly diverse bacterial communities, whose composition was very different from that of surrounding bacterioplankton. This high total biodiversity of skin-associated communities was supported by the important variability, between host species, individuals and the different body parts (dorsal, anal, pectoral and caudal fins).

English syllable confusion and imitation in Korean bilingual and monolingual children and adults

In the present study, Korean-English bilingual (KEB) and Korean monolingual (KM) children, between the ages of 8 and 13 years, and KEB adults, ages 18 and older, were examined with one speech perception task, called the Nonsense Syllable Confusion Matrix (NSCM) task (Allen, 2005), and two production tasks, called the Nonsense Syllable Imitation Task (NSIT) and the Nonword Repetition Task (NRT; Dollaghan & Campbell, 1998). The present study examined (a) which English sounds on the NSCM task were identified less well, presumably due to interference from Korean phonology, in bilinguals learning English as a second language (L2) and in monolinguals learning English as a foreign language (FL); (b) which English phonemes on the NSIT were more challenging for bilinguals and monolinguals to produce; (c) whether perception on the NSCM task is related to production on the NSIT, or phonological awareness, as measured by the NRT; and (d) whether perception and production differ in three age-language status groups (i.e., KEB children, KEB adults, and KM children) and in three proficiency subgroups of KEB children (i.e., English-dominant, ED; balanced, BAL; and Korean-dominant, KD). In order to determine English proficiency in each group, language samples were extensively and rigorously analyzed, using software, called Systematic Analysis of Language Transcripts (SALT). Length of samples in complete and intelligible utterances, number of different and total words (NDW and NTW, respectively), speech rate in words per minute (WPM), and number of grammatical errors, mazes, and abandoned utterances were measured and compared among the three initial groups and the three proficiency subgroups. Results of the language sample analysis (LSA) showed significant group differences only between the KEBs and the KM children, but not between the KEB children and adults. Nonetheless, compared to normative means (from a sample length- and age-matched database provided by SALT), the KEB adult group and the KD subgroup produced English at significantly slower speech rates than expected for monolingual, English-speaking counterparts. Two existing models of bilingual speech perception and production—the Speech Learning Model or SLM (Flege, 1987, 1992) and the Perceptual Assimilation Model or PAM (Best, McRoberts, & Sithole, 1988; Best, McRoberts, & Goodell, 2001)—were considered to see if they could account for the perceptual and production patterns evident in the present study. The selected English sounds for stimuli in the NSCM task and the NSIT were 10 consonants, /p, b, k, g, f, θ, s, z, ʧ, ʤ/, and 3 vowels /I, ɛ, æ/, which were used to create 30 nonsense syllables in a consonant-vowel structure. Based on phonetic or phonemic differences between the two languages, English sounds were categorized either as familiar sounds—namely, English sounds that are similar, but not identical, to L1 Korean, including /p, k, s, ʧ, ɛ/—or unfamiliar sounds—namely, English sounds that are new to L1, including /b, g, f, θ, z, ʤ, I, æ/. The results of the NSCM task showed that (a) consonants were perceived correctly more often than vowels, (b) familiar sounds were perceived correctly more often than unfamiliar ones, and (c) familiar consonants were perceived correctly more often than unfamiliar ones across the three age-language status groups and across the three proficiency subgroups; and (d) the KEB children perceived correctly more often than the KEB adults, the KEB children and adults perceived correctly more often than the KM children, and the ED and BAL subgroups perceived correctly more often than the KD subgroup. The results of the NSIT showed (a) consonants were produced more accurately than vowels, and (b) familiar sounds were produced more accurately than unfamiliar ones, across the three age-language status groups. Also, (c) familiar consonants were produced more accurately than unfamiliar ones in the KEB and KM child groups, and (d) unfamiliar vowels were produced more accurately than a familiar one in the KEB child group, but the reverse was true in the KEB adult and KM child groups. The KEB children produced sounds correctly significantly more often than the KM children and the KEB adults, though the percent correct differences were smaller than for perception. Production differences were not found among the three proficiency subgroups. Perception on the NSCM task was compared to production on the NSIT and NRT. Weak positive correlations were found between perception and production (NSIT) for unfamiliar consonants and sounds, whereas a weak negative correlation was found for unfamiliar vowels. Several correlations were significant for perceptual performance on the NSCM task and overall production performance on the NRT: for unfamiliar consonants, unfamiliar vowels, unfamiliar sounds, consonants, vowels, and overall performance on the NSCM task. Nonetheless, no significant correlation was found between production on the NSIT and NRT. Evidently these are two very different production tasks, where immediate imitation of single syllables on the NSIT results in high performance for all groups. Findings of the present study suggest that (a) perception and production of L2 consonants differ from those of vowels; (b) perception and production of L2 sounds involve an interaction of sound type and familiarity; (c) a weak relation exists between perception and production performance for unfamiliar sounds; and (d) L2 experience generally predicts perceptual and production performance. The present study yields several conclusions. The first is that familiarity of sounds is an important influence on L2 learning, as claimed by both SLM and PAM. In the present study, familiar sounds were perceived and produced correctly more often than unfamiliar ones in most cases, in keeping with PAM, though experienced L2 learners (i.e., the KEB children) produced unfamiliar vowels better than familiar ones, in keeping with SLM. Nonetheless, the second conclusion is that neither SLM nor PAM consistently and thoroughly explains the results of the present study. This is because both theories assume that the influence of L1 on the perception of L2 consonants and vowels works in the same way as for production of them. The third and fourth conclusions are two proposed arguments: that perception and production of consonants are different than for vowels, and that sound type interacts with familiarity and L2 experience. These two arguments can best explain the current findings. These findings may help us to develop educational curricula for bilingual individuals listening to and articulating English. Further, the extensive analysis of spontaneous speech in the present study should contribute to the specification of parameters for normal language development and function in Korean-English bilingual children and adults.

Biological Inspiration for Artificial Immune Systems

Artificial immune systems (AISs) to date have generally been inspired by naive biological metaphors. This has limited the effectiveness of these systems. In this position paper two ways in which AISs could be made more biologically realistic are discussed. We propose that AISs should draw their inspiration from organisms which possess only innate immune systems, and that AISs should employ systemic models of the immune system to structure their overall design. An outline of plant and invertebrate immune systems is presented, and a number of contemporary systemic models are reviewed. The implications for interdisciplinary research that more biologically-realistic AISs could have is also discussed.

NFL-lipid nanocapsules for brain neural stem cell targeting in vitro and in vivo

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