A kernel clustering algorithm based on diameters

This paper analyzes an iterative kernel partitioning clustering algorithm that dynamically merges, removes and adds clusters using some characteristics, like the radii and diameters of the clusters, and distance between centers. The clustering is carried out in feature space in terms of a kernel function so that non-linearly separable clusters are identified. The preliminary experiments with seven datasets show that the proposed algorithm is able to successfully converge to the expected clustering. It is also shown that the algorithm performance is sensitive to the parameter σ of the Gaussian kernel.This work has been supported by FCT – Funda¸c˜ao para a Ciˆencia e Tecnologia within the R&D Units Project Scope: UIDB/00319/2020, UIDB/00013/2020 and UIDP/00013/2020 of CMAT-U

Bio-Guided Optimization of Cystoseira abies-marina Cosmeceuticals Extraction by Advanced Technologies

Cystoseira abies-marina (reclassified as Gongolaria abies-marina) is a brown seaweed species rich in meroterpenoids, presenting interesting antioxidant, antitumor, and anti-inflammatory activities. However, there is still a lot to uncover regarding the bioactive potential of this species, as evidenced by the lack of records of antiaging activities from Cystoseira abies-marina, making this macroalga an excellent candidate for studies of its cosmeceutical potential. Ultrasound-(UAE) and microwave-assisted extraction (MAE) are advanced sustainable technologies that are very efficient in enhancing bioactive compound extraction. Applying these extraction techniques to a new biological matrix often calls for optimizing the parameters toward the best extraction yield. Since Cystoseira abies-marina is a new matrix for both UAE and MAE techniques, the present work proposes the optimization of the extraction process, using a novel approach: instead of only focusing on increasing the yield, the goal of this work is to determine the parameters for UAE and MAE that lead to extracts with better antiaging activities. For this bio-guided approach, several Cystoseira abies-marina extracts were prepared by UAE and MAE under varying conditions of solvent, time, and algae/solvent ratios. Their antiaging activities were then determined, and all the results combined to unveil the conditions yielding extracts with higher cosmeceutical potential. Using statistical tools, it was found that, for UAE, the best conditions were ethyl acetate, 15 min, and a ratio of 1:4, which led to an extract with high yield, and causing the strong inhibition of tyrosinase and elastase. In turn, ethanol, 10 min, and a ratio of 1:4 were the best conditions for MAE, leading to the extract with the best antioxidant activity. The results show that the proposed bio-guided approach was effective in obtaining extracts with high cosmeceutical potential, unveiling the possibility of modulating an extract’s activity by changing the extraction method.FUNDING: Thanks are due to FCT—Fundação para a Ciência e a Tecnologia for supporting G.P.R.’s grant (SFRH/BD/144446/2019), through National and European Funds and co-financed by the European Social Fund through the Regional Operational Programme Centro 2020, as well as to FCT, the European Union, QREN, FEDER, and COMPETE, through funding the cE3c center (UIDB/00329/2020). This work received financial support from PT National Funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through projects UIDB/50006/2020 and UIDP/50006/2020. A.F.P. thanks FCT for funding through the Individual Call to Scientific Employment Stimulus (2020.01614.CEECIND/CP1596/CT0007).info:eu-repo/semantics/publishedVersio

Valorizing coffee silverskin based on its phytochemicals and antidiabetic potential: from lab to a pilot scale

This study investigates the possibility of valorizing coffee silverskin through the recovery of its bioactive compounds using a sustainable extraction method that could be industrially applied. For that, aqueous extracts were prepared using ultrasonic-assisted extraction (laboratorial scale) and, for comparison, a scale-up of the process was developed using the Multi-frequency Multimode Modulated technology. A concentration procedure at the pilot scale was also tested. The three types of extracts obtained were characterized regarding caffeine and chlorogenic acids contents, and the effects on intestinal glucose and fructose uptake (including sugar transporters expression) in human intestinal epithelial (Caco-2) cells were ascertained. The phytochemical contents of the extracts prepared at the laboratory and pilot scale were comparable (caffeine: 27.7 vs. 29.6 mg/g freeze-dried extract; 3-, 4-, and 5-caffeoylquinic acids: 0.19 vs. 0.31, 0.15 vs. 0.42, and 1.04 vs. 1.98 mg/g, respectively; 4- and 5- feruloylquinic acids: 0.39 vs. 0.43 and 1.05 vs. 1.32 mg/g, respectively). Slight differences were noticed according to the extracts preparation steps, but in general, all the extracts promoted significant inhibitions of [1,2-3H(N)]-deoxy-D-glucose and 14C-D-fructose uptake, which resulted mainly from a decrease on the facilitative glucose transporter 2 (GLUT2) and sodium-glucose linked transporter 1 (SGLT1) genes expression but not on the expression of the facilitative glucose transporter 5 (GLUT5) gene. Moreover, a synergistic effect of caffeine and 5-caffeoylquinic acid on sugars uptake was found. The results clearly show that the Multi-frequency Multimode Modulated technology is a viable option to be applied at an industrial level to recover bioactive components from silverskin and obtain extracts with antidiabetic potential that could be used to develop functional food products or dietary supplements.The open access publication fee of this paper was funded by the AgriFood XXI I&D&I project (NORTE-01-0145-FEDER-000041) cofinanced by European Regional Development Fund (ERDF) through the NORTE 2020 (Programa Operacional Regional do Norte 2014/2020)

Fluorescence studies on new potential antitumoral 1,3-diarylurea derivatives in the thieno[3,2-b]pyridine series encapsulated in magnetoliposomes

Magnetic nanoparticles of magnetite and of nickel core with silica shell were prepared and either covered with a lipid bilayer or entrapped in liposomes, forming magnetoliposomes. New potential antitumoral 1,3-diarylurea derivatives of thieno[3,2-b]pyridines were then encapsulated in liposomes and magnetoliposomes and their photophysical behavior was investigated.Fundação para a Ciência e a Tecnologia (FCT), FEDER, COMPETE/QREN/EU for financial support to CFUM (PEst-C/FIS/UI0607/2011) and CQ/UM (PEst-C/QUI/UI0686/2011) and to research projects PTDC/QUI/81238/2006 (FCOMP-01-0124-FEDER-007467), PTDC/QUIQUI/111060/2009 (FCOMP-01-0124-FEDER-015603)

New 1,3-diarylureas linked by C-C Suzuki coupling to the methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate moiety: synthesis and fluorescence studies in solution and in lipid membranes

New six fluorescent 1,3-diarylureas linked by C-C Suzuki coupling to the 6-position of the methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate moiety were prepared by reaction of the amino groups on the ortho or meta positions relative to the C-C bond of the Suzuki coupling products, with different para-substituted arylisocyanates (H, OMe, CN), in high to excellent yields. The fluorescence properties of the 1,3-diarylureas in solution and in lipid membranes of egg-yolk phosphatidylcholine (Egg-PC), dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylglycerol (DPPG) or dioctadecyldimethylammonium bromide (DODAB), with or without cholesterol (Ch), were studied. The six 1,3-diarylureas have reasonable fluorescence quantum yields in several solvents (between 0.02 and 0.69) and present a moderately solvent sensitive emission, but are not fluorescent in alcohols and water. The compounds bearing the arylurea moiety in the meta position relative to the C-C bond, especially with the OMe and CN substituents, present the better solvatochromic properties. Incorporation of the six compounds in lipid membranes indicates that all the compounds are deeply located in the hydrophobic region of the lipid bilayers, feeling the transition between the rigid gel phase and fluid phases.To the Foundation for the Science and Technology (FCT, Portugal) for inancial support to the NMR portuguese network (PTNMR, Bruker Avance III 400-Univ. Minho). To the FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support to the Research Centres, CQ/UM [PEst-C/QUI/UI0686/2011 (FCOMP-01-0124-FEDER-022716)] and CFUM [PEst-C/FIS/UI0607/2011 (F-COMP-01-0124-FEDER-022711)], and to the research projects PTDC/QUI/81238/2006 (FCOMP-01-0124-FEDER-007467) (photophysical studies) and PTDC/QUI-QUI/111060/2009 (F-COMP-01-0124-FEDER-015603) (organic synthesis)

Evaluation of two methods for computational HLA haplotypes inference using a real dataset

<p>Abstract</p> <p>Background</p> <p>HLA haplotype analysis has been used in population genetics and in the investigation of disease-susceptibility locus, due to its high polymorphism. Several methods for inferring haplotype genotypic data have been proposed, but it is unclear how accurate each of the methods is or which method is superior. The accuracy of two of the leading methods of computational haplotype inference – Expectation-Maximization algorithm based (implemented in Arlequin V3.0) and Bayesian algorithm based (implemented in PHASE V2.1.1) – was compared using a set of 122 HLA haplotypes (A-B-Cw-DQB1-DRB1) determined through direct counting. The accuracy was measured with the Mean Squared Error (<it>MSE</it>), Similarity Index (<it>I</it>_<it>F</it>) and Haplotype Identification Index (<it>I</it>_<it>H</it>).</p> <p>Results</p> <p>None of the methods inferred all of the known haplotypes and some differences were observed in the accuracy of the two methods in terms of both haplotype determination and haplotype frequencies estimation. Working with haplotypes composed by low polymorphic sites, present in more than one individual, increased the confidence in the assignment of haplotypes and in the estimation of the haplotype frequencies generated by both programs.</p> <p>Conclusion</p> <p>The PHASE v2.1.1 implemented method had the best overall performance both in haplotype construction and frequency calculation, although the differences between the two methods were insubstantial. To our knowledge this was the first work aiming to test statistical methods using real haplotypic data from the HLA region.</p

New potential antitumoral di(hetero)arylether derivatives in the thieno[3,2-b]pyridine series : synthesis and fluorescence studies in solution and in nanoliposomes

New fluorescent methoxylated di(hetero)arylethers in the thieno[3,2-b]pyridine series were prepared by a copper-catalyzed Ullmann-type C-O coupling of the methyl 3-amino-6-bromothieno[3,2-b]pyridine-2-carboxylate with ortho, meta and para-methoxyphenols, using N,N-dimethylglycine as the ligand and Cs2CO3 as the base. The compounds obtained were tested for their inhibitory growth activity in three human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer). The di(hetero)arylethers bearing a methoxy group in the ortho and meta positions showed very low GI50 values (1.1 - 2.5 µM) in all the three tumor cell lines. Their fluorescence properties in solution and when encapsulated in different nanoliposome formulations, composed either by egg-yolk phosphatidylcholine (Egg-PC), dipalmitoyl phosphatidylcholine (DPPC), dimyristoyl phosphatidylglycerol (DMPG), dioctadecyldimethylammonium bromide (DODAB), distearoyl phosphatidylcholine (DSPC), with or without cholesterol (Ch), or distearoyl phosphatidylethanolamine-(polyethylene glycol)2000 (DSPE-PEG), were studied. All compounds can be carried in the hydrophobic region of the liposome membrane. The liposomes with incorporated compounds are nanometric in size (diameter lower than 150 nm) and have generally low polydispersity.Fundação para a Ciência e a Tecnologia (FCT) - Bruker Avance III 400-Univ. Minho).Fundo Europeu de Desenvolvimento Regional (FEDER)Research Centres, CQ/UM - PEstC/QUI/UI0686/2011, FCOMP-01-0124-FEDER-022716)] and CFUM [PEst-C/FIS/UI0607/2011, F-COMP-01-0124-FEDER-022711)], PTDC/QUI/81238/2006, (FCOMP-01-0124-FEDER-007467) (photophysical studies), PTDC/QUI-QUI/111060/2009 (F-COMP-01-0124-FEDER-015603) (organic synthesis and biological studies)COMPETE/QREN/EU

Anti-trichomonas vaginalis activity of saponins from Ilex paraguariensis ("mate") fruits

This study evaluates the in vitro anti-trichomonads activity of a saponin enriched fraction (MSF) obtained from the fruits of Ilex paraguariensis A. St. Hil. (Aquifoliaceae). The MSF showed better anti-trichomonads activity than polysorbate and tyloxapol. A similar activity was obtained for quillaja saponins, but this fraction presented the highest cytotoxicity to mammalian cells as follows: quillaja > tyloxapol > polysorbate 80 > MSF. Neither the co-addition of MSF and metronidazole (MTZ) nor the pretreatment of the trophozoites with MSF prior to the addition of MTZ elicited a significant effect on MTZ activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Roles of non-coding RNA in sugarcane-microbe interaction

Studies have highlighted the importance of non-coding RNA regulation in plant-microbe interaction. However, the roles of sugarcane microRNAs (miRNAs) in the regulation of disease responses have not been investigated. Firstly, we screened the sRNA transcriptome of sugarcane infected with Acidovorax avenae. Conserved and novel miRNAs were identified. Additionally, small interfering RNAs (siRNAs) were aligned to differentially expressed sequences from the sugarcane transcriptome. Interestingly, many siRNAs aligned to a transcript encoding a coppertransporter gene whose expression was induced in the presence of A. avenae, while the siRNAs were repressed in the presence of A. avenae. Moreover, a long intergenic non-coding RNA was identified as a potential target or decoy of miR408. To extend the bioinformatics analysis, we carried out independent inoculations and the expression patterns of six miRNAs were validated by quantitative reverse transcription-PCR (qRT-PCR). Among these miRNAs, miR408—a copper- microRNA—was downregulated. The cleavage of a putative miR408 target, a laccase, was confirmed by a modified 50RACE (rapid amplification of cDNA ends) assay. MiR408 was also downregulated in samples infected with other pathogens, but it was upregulated in the presence of a beneficial diazotrophic bacteria. Our results suggest that regulation by miR408 is important in sugarcane sensing whether microorganisms are either pathogenic or beneficial, triggering specific miRNA-mediated regulatory mechanisms accordingly

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies $E>E_{th}=5.5\times 10^{19}$ eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at $E>E_{th}$ are heavy nuclei with charge $Z$, the proton component of the sources should lead to excesses in the same regions at energies $E/Z$. We here report the lack of anisotropies in these directions at energies above $E_{th}/Z$ (for illustrative values of $Z=6,\ 13,\ 26$). If the anisotropies above $E_{th}$ are due to nuclei with charge $Z$, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies