Evolutionary Generalized Radial Basis Function neural networks for improving prediction accuracy in gene classification using feature selection

Radial Basis Function Neural Networks (RBFNNs) have been successfully employed in several function approximation and pattern recognition problems. The use of different RBFs in RBFNN has been reported in the literature and here the study centres on the use of the Generalized Radial Basis Function Neural Networks (GRBFNNs). An interesting property of the GRBF is that it can continuously and smoothly reproduce different RBFs by changing a real parameter τ. In addition, the mixed use of different RBF shapes in only one RBFNN is allowed. Generalized Radial Basis Function (GRBF) is based on Generalized Gaussian Distribution (GGD), which adds a shape parameter, τ, to standard Gaussian Distribution. Moreover, this paper describes a hybrid approach, Hybrid Algorithm (HA), which combines evolutionary and gradient-based learning methods to estimate the architecture, weights and node topology of GRBFNN classifiers. The feasibility and benefits of the approach are demonstrated by means of six gene microarray classification problems taken from bioinformatic and biomedical domains. Three filters were applied: Fast Correlation-Based Filter (FCBF), Best Incremental Ranked Subset (BIRS), and Best Agglomerative Ranked Subset (BARS); this was done in order to identify salient expression genes from among the thousands of genes in microarray data that can directly contribute to determining the class membership of each pattern. After different gene subsets were obtained, the proposed methodology was performed using the selected gene subsets as new input variables. The results confirm that the GRBFNN classifier leads to a promising improvement in accuracy.     

Strong accumulators from collision-resistant hashing

Accumulator schemes were introduced in order to represent a large set of values as one short value called the accumulator. These schemes allow one to generate membership proofs, that is, short witnesses that a certain value belongs to the set. In universal accumulator schemes, efficient proofs of non-membership can also be created. Li et?al. (Proceedings of applied cryptography and network security—ACNS ’07, LNCS, vol 4521, 2007), building on the work of Camenisch and Lysyanskaya (Advances in cryptology—proceedings of Crypto ’02, LNCS, vol 2442. Springer, Berlin, pp 61–76, 2002), proposed an efficient accumulator scheme, which relies on a trusted accumulator manager. Specifically, a manager that correctly performs accumulator updates. In this work, we introduce the notion of strong universal accumulator schemes, which are similar in functionality to universal accumulator schemes, but do not assume the accumulator manager is trusted. We also formalize the security requirements for such schemes. We then give a simple construction of a strong universal accumulator scheme, which is provably secure under the assumption that collision-resistant hash functions exist. The weaker requirement on the accumulator manager comes at a price; our scheme is less efficient than known universal accumulator schemes—the size of (non)membership witnesses is logarithmic in the size of the accumulated set in contrast to constant in the scheme of Camenisch and Lysyanskaya. Finally, we show how to use strong universal accumulators to solve a problem of practical relevance, the so-called e-Invoice Factoring Problem.     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

The GAUGAA Motif Is Responsible for the Binding between circSMARCA5 and SRSF1 and Related Downstream Effects on Glioblastoma Multiforme Cell Migration and Angiogenic Potential

Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential.     

Confocal Blood Flow Videomicroscopy of Thrombus Formation over Human Arteries and Local Targeting of P2X7

Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy.     

Silicon Nitride Derived from an Organometallic Polymeric Precursor: Preparation and Characterization

Partially crystalline Si₃N₄, with nanosized crystals and a specific surface area greater than 200 m²/g, is obtained by pyrolysis of a commercially available vinylic polysilane in a stream of anhydrous NH₃ to 1000°C. This polymer does not contain N initially. Crystallization to high-purity α-Si₃N₄ proceeds with additional heating above 1400°C under N₂. The changes in crystallinity, powder morphology, infrared spectra, and elemental compositions, for samples annealed from 1000° to 1600°C under N₂, are consistent with an amorphous-to-crystalline transformation. Although macroscopic consolidation and local densification occur at 1400°C, volatilization and accompanying weight loss limit bulk densification. The effect of temperature on specific surface area is examined and related to the sintering process. These results are applicable to pyrolysis, decomposition, and crystallization studies of ceramics synthesized by polymeric precursor routes.     

Design of fluidized bed photoreactors: Optical properties of photocatalytic composites of titania CVD-coated onto quartz sand

Volumetric optical properties (spectral absorption, scattering and extinction coefficients) of differently expanded narrow-path fluidized beds (FB) of a photocatalyst obtained by plasma-CVD deposition of titania onto quartz sand, relevant for photoreactor design purposes, are determined by using an unidirectional and unidimensional (1DD) model for the solution of the radiative transfer equation (RTE). Two simplified approaches are used: a Kubelka-Munk (KM) type of solution, by which the RTE is transformed into a pair of ordinary differential equations, and a discrete ordinate method (DOM) by which the complete RTE is transformed into an algebraic system that can be solved computationally. The second approach was validated by introducing the obtained optical parameters into a more elaborated bi-directional and two-dimensional (2DD) DOM model. Despite its simplicity, the KM method was able to yield fair order-of-magnitude estimates of the spectral optical properties of these FB.     

Styrene-butadiene branched star-shaped asphalt modifiers: Synthesis and mechanical characterization

Abstract

The synthesis and the corresponding characterization of styrene-butadiene (SB), branched, star-shaped copolymers was investigated as part of a research project on asphalt modification using polymers with precise molecular structures. The method of anionic polymerization was followed to prepare samples of block copolymers of SB, a synthesis method that controls chain-architecture, molecular weight distribution, monomer distribution, and the average molecular weight. The research studies are the synthesis of block copolymers including linear, three- and four-arms constructs, depending on the coupling agent used. The techniques of nuclear magnetic resonance (1NMR), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and rheology were carried out to characterize the copolymers. From the results of the 1NMR, DSC, and GPC analyses, all star-shaped copolymers investigated showed a similar block copolymer composition. Furthermore, the rheological behavior of one of the synthesized star-shaped copolymers was nearly the same as a four-branched commercial copolymer. Rheologically, the four-arm block copolymer sample had the largest storage modulus (G′) among the branched copolymers synthetized, indicating that such architecture produces a highly structured material. In regard to polymer-modified asphalt formulations, the three-branched copolymer architecture yielded better elastic behavior than the four-branch version. In summary, the findings of this investigation provide new insight about a polymer system that may offer advantages in industrial asphalt paving applications.     

Resolution proof transformation for compression and interpolation

Verification methods based on SAT, SMT, and theorem proving often rely on proofs of unsatisfiability as a powerful tool to extract information in order to reduce the overall effort. For example a proof may be traversed to identify a minimal reason that led to unsatisfiability, for computing abstractions, or for deriving Craig interpolants. In this paper we focus on two important aspects that concern efficient handling of proofs of unsatisfiability: compression and manipulation. First of all, since the proof size can be very large in general (exponential in the size of the input problem), it is indeed beneficial to adopt techniques to compress it for further processing. Secondly, proofs can be manipulated as a flexible preprocessing step in preparation for interpolant computation. Both these techniques are implemented in a framework that makes use of local rewriting rules to transform the proofs. We show that a careful use of the rules, combined with existing algorithms, can result in an effective simplification of the original proofs. We have evaluated several heuristics on a wide range of unsatisfiable problems deriving from SAT and SMT test cases.     

The annual cycle of Flehmen in black-tailed deer (Odocoileus hemionus columbianus)

Flehmen is a stereotyped response of ungulates and other mammals to urine. In black-tailed deer, Flehmen occurs typically in males (rarely in females), and its frequency shows an annual cycle. Flehmen in response to female urine was most frequent in November, and to male urine in January. The response minimum to both types of urine occurred in May. Fifty-five to 100% of initial responses to female urine resulted in Flehmen. The deer responded more often to female urine, and the difference between the responses to female and male urine increased from May to November. A male's own urine released Flehmen more often than did urine of other males. The response intensity varied with the spatial orientation of the male to the urinating female, and responses were usually limited to distances of 15 m or less.