Hyers-Ulam-Rassias Stability of Functional Differential Systems with Point and Distributed Delays

This paper investigates stability and asymptotic properties of the error with respect to its nominal version of a nonlinear time-varying perturbed functional differential system subject to point, finite-distributed, and Volterra-type distributed delays associated with linear dynamics together with a class of nonlinear delayed dynamics. The boundedness of the error and its asymptotic convergence to zero are investigated with the results being obtained based on the Hyers-Ulam-Rassias analysis.

On contractive cyclic fuzzy maps in metric spaces and some related results on fuzzy best proximity points and fuzzy fixed points

This paper investigates some properties of cyclic fuzzy maps in metric spaces. The convergence of distances as well as that of sequences being generated as iterates defined by a class of contractive cyclic fuzzy mapping to fuzzy best proximity points of (non-necessarily intersecting adjacent subsets) of the cyclic disposal is studied. An extension is given for the case when the images of the points of a class of contractive cyclic fuzzy mappings restricted to a particular subset of the cyclic disposal are allowed to lie either in the same subset or in its next adjacent one.

Involvement of ANXA5 and ILKAP in Susceptibility to Malignant Melanoma

Single nucleotide-polymorphisms (SNPs) are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM) have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588) located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12-1.48; p-value= 4x10(-4)). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocytes.

Pharmacogenetics of MicroRNAs and MicroRNAs Biogenesis Machinery in Pediatric Acute Lymphoblastic Leukemia

Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.

Evaluation of Fentanyl Disposition and Effects in Newborn Piglets as an Experimental Model for Human Neonates

Background: Fentanyl is widely used off-label in NICU. Our aim was to investigate its cerebral, cardiovascular and pulmonary effects as well as pharmacokinetics in an experimental model for neonates. Methods: Fentanyl (5 mu g/kg bolus immediately followed by a 90 minute infusion of 3 mu g/kg/h) was administered to six mechanically ventilated newborn piglets. Cardiovascular, ventilation, pulmonary and oxygenation indexes as well as brain activity were monitored from T = 0 up to the end of experiments (T = 225-300 min). Also plasma samples for quantification of fentanyl were drawn. Results: A "reliable degree of sedation" was observed up to T = 210-240 min, consistent with the selected dosing regimen and the observed fentanyl plasma levels. Unlike cardiovascular parameters, which were unmodified except for an increasing trend in heart rate, some of the ventilation and oxygenation indexes as well as brain activity were significantly altered. The pulmonary and brain effects of fentanyl were mostly recovered from T = 210 min to the end of experiment. Conclusion: The newborn piglet was shown to be a suitable experimental model for studying fentanyl disposition as well as respiratory and cardiovascular effects in human neonates. Therefore, it could be extremely useful for further investigating the drug behaviour under pathophysiological conditions.

Synthesis and stereochemical assignments of diastereomeric Ni(II) complexes of glycine Schiff base with (R)-2-(N-{2-[N-alkyl-N-(1-phenylethyl)-amino]acetyl}amino) benzophenone; a case of configurationally stable stereogenic nitrogen

A family of chiral ligands derived from alpha-phenylethylamine and 2-aminobenzophenone were prepared by alkylation of the nitrogen atom. Upon reaction with glycine and a Ni(II) salt, these ligands were transformed into diastereomeric complexes, as a result of the configurational stability of the stereogenic nitrogen atom. Different diastereomeric ratios were observed depending on the substituent R introduced in the starting ligand, and stereochemical assignments were based on X-ray analysis, along with NMR studies and optical rotation measurements.

Temperature-and pH-Sensitive Nanohydrogels of Poly(N-Isopropylacrylamide) for Food Packaging Applications: Modelling the Swelling-Collapse Behaviour

Temperature-sensitive poly(N-isopropylacrylamide) (PNIPA) nanohydrogels were synthesized by nanoemulsion polymerization in water-in-oil systems. Several cross-linking degrees and the incorporation of acrylic acid as comonomer at different concentrations were tested to produce nanohydrogels with a wide range of properties. The physicochemical properties of PNIPA nanohydrogels, and their relationship with the swelling-collapse behaviour, were studied to evaluate the suitability of PNIPA nanoparticles as smart delivery systems (for active packaging). The swelling-collapse transition was analyzed by the change in the optical properties of PNIPA nanohydrogels using ultraviolet-visible spectroscopy. The thermodynamic parameters associated with the nanohydrogels collapse were calculated using a mathematical approach based on the van't Hoff analysis, assuming a two-state equilibrium (swollen to collapsed). A mathematical model is proposed to predict both the thermally induced collapse, and the collapse induced by the simultaneous action of two factors (temperature and pH, or temperature and organic solvent concentration). Finally, van't Hoff analysis was compared with differential scanning calorimetry. The results obtained allow us to solve the problem of determining the molecular weight of the structural repeating unit in cross-linked NIPA polymers, which, as we show, can be estimated from the ratio of the molar heat capacity (obtained from the van't Hoff analysis) to the specific heat capacity (obtained from calorimetric measurements).

Biotic vs. Abiotic Control of Decomposition: A Comparison of the Effects of Simulated Extinctions and Changes in Temperature

The loss of species is known to have significant effects on ecosystem functioning, but only recently has it been recognized that species loss might rival the effects of other forms of environmental change on ecosystem processes. There is a need for experimental studies that explicitly manipulate species richness and environmental factors concurrently to determine their relative impacts on key ecosystem processes such as plant litter decomposition. It is crucial to understand what factors affect the rate of plant litter decomposition and the relative magnitude of such effects because the rate at which plant litter is lost and transformed to other forms of organic and inorganic carbon determines the capacity for carbon storage in ecosystems and the rate at which greenhouse gasses such as carbon dioxide are outgassed. Here we compared how an increase in water temperature of 5 degrees C and loss of detritivorous invertebrate and plant litter species affect decomposition rates in a laboratory experiment simulating stream conditions. Like some prior studies, we found that species identity, rather than species richness per se, is a key driver of decomposition, but additionally we showed that the loss of particular species can equal or exceed temperature change in its impact on decomposition. Our results indicate that the loss of particular species can be as important a driver of decomposition as substantial temperature change, but also that predicting the relative consequences of species loss and other forms of environmental change on decomposition requires knowledge of assemblages and their constituent species' ecology and ecophysiology

Association between CASP8-652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study

The common 2652 6N del variant in the CASP8 promoter (rs3834129) has been described as a putative low-penetrance risk factor for different cancer types. In particular, some studies suggested that the deleted allele (del) was inversely associated with CRC risk while other analyses failed to confirm this. Hence, to better understand the role of this variant in the risk of developing CRC, we performed a multi-centric case-control study. In the study, the variant 2652 6N del was genotyped in a total of 6,733 CRC cases and 7,576 controls recruited by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (COlorectal cancer GENeTics). Our analysis indicated that rs3834129 was not associated with CRC risk in the full data set. However, the del allele was under-represented in one set of cases with a family history of CRC (per allele model OR = 0.79, 95% CI = 0.69-0.90) suggesting this allele might be a protective factor versus familial CRC. Since this multi-centric case-control study was performed on a very large sample size, it provided robust clarification of the effect of rs3834129 on the risk of developing CRC in Caucasians.

Sylphella puccoon gen. n., sp n. and two additional new species of aquatic oligochaetes (Lumbriculidae, Clitellata) from poorly-known lotic habitats in North Carolina (USA)

Three new species of Lumbriculidae were collected from floodplain seeps and small streams in southeastern North America. Some of these habitats are naturally acidic. Sylphella puccoon gen. n., sp. n. has prosoporous male ducts in X-XI, and spermathecae in XII-XIII. Muscular, spherical atrial ampullae and acuminate penial sheaths distinguish this monotypic new genus from other lumbriculid genera having similar arrangements of reproductive organs. Cookidrilus pocosinus sp. n. resembles its two subterranean, Palearctic congeners in the arrangement of reproductive organs, but is easily distinguished by the position of the spermathecal pores in front of the chaetae in X-XIII. Stylodrilus coreyi sp. n. differs from congeners having simple-pointed chaetae and elongate atria primarily by the structure of the male duct and the large clusters of prostate cells. Streams and wetlands of Southeastern USA have a remarkably high diversity of endemic lumbriculids, and these poorly-known invertebrates should be considered in conservation efforts.

Physico-chemical interactions between compartment-forming lipids and other prebiotically relevant biomolecules

Lipids are essential constituents of contemporary living cells, serving as structural molecules that are necessary to form membranous compartments. Amphiphilic lipid-like molecules may also have contributed to prebiotic chemical evolution by promoting the synthesis, aggregation and cooperative encapsulation of other biomolecules. The resulting compartments would allow systems of molecules to be maintained that represent microscopic experiments in a natural version of combinatorial chemistry. Here we address these possibilities and describe recent results related to interactions between amphiphiles and other biomolecules during early evolution toward the first living cells.

Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.

Approximate Solutions by Truncated Taylor Series Expansions of Nonlinear Differential Equations and Related Shadowing Property with Applications

This paper investigates the errors of the solutions as well as the shadowing property of a class of nonlinear differential equations which possess unique solutions on a certain interval for any admissible initial condition. The class of differential equations is assumed to be approximated by well-posed truncated Taylor series expansions up to a certain order obtained about certain, in general nonperiodic, sampling points t(i) is an element of [t(0), t(J)] for i = 0, 1, . . . , J of the solution. Two examples are provided.

Convergence Properties and Fixed Points of Two General Iterative Schemes with Composed Maps in Banach Spaces with Applications to Guaranteed Global Stability

This paper investigates the boundedness and convergence properties of two general iterative processes which involve sequences of self-mappings on either complete metric or Banach spaces. The sequences of self-mappings considered in the first iterative scheme are constructed by linear combinations of a set of self-mappings, each of them being a weighted version of a certain primary self-mapping on the same space. The sequences of self-mappings of the second iterative scheme are powers of an iteration-dependent scaled version of the primary self-mapping. Some applications are also given to the important problem of global stability of a class of extended nonlinear polytopic-type parameterizations of certain dynamic systems.

Analysis of the Response Speed of Musculature of the Knee in Professional Male and Female Volleyball Players

The aim of this study was to evaluate the normalized response speed (Vrn) of the knee musculature (flexor and extensor) in high competitive level volleyball players using tensiomyography (TMG) and to analyze the muscular response of the vastus medialis (VM), rectus femoris (RF), vastus lateralis (VL), and biceps femoris (BF) in accordance with the specific position they play in their teams. One hundred and sixty-six players (83 women and 83 men) were evaluated. They belonged to eight teams in the Spanish women's superleague and eight in the Spanish men's superleague. The use of Vrn allows avoiding possible sample imbalances due to anatomical and functional differences and demands. We found differences between Vrn in each of the muscles responsible for extension (VM, RF, and VL) and flexion (BF) regardless of the sex. Normalized response speed differences seem to be larger in setters, liberos and outside players compared to middle blockers and larger in males when compared to females. These results of Vrn might respond to the differences in the physical and technical demands of each specific position, showing an improved balance response of the knee extensor and flexor musculature in male professional volleyball players.