Counter-ion effect on surfactant-DNA gel particles as controlled DNA delivery systems

The ability to entrap drugs within vehicles and subsequently release them has led to new treatments for a number of diseases. Based on an associative phase separation and interfacial diffusion approach, we developed a way to prepare DNA gel particles without adding any kind of cross-linker or organic solvent. Among the various agents studied, cationic surfactants offered particularly efficient control for encapsulation and DNA release from these DNA gel particles. The driving force for this strong association is the electrostatic interaction between the two components, as induced by the entropic increase due to the release of the respective counter-ions. However, little is known about the influence of the respective counter-ions on this surfactant-DNA interaction. Here we examined the effect of different counter-ions on the formation and properties of the DNA gel particles by mixing DNA (either single- (ssDNA) or double-stranded (dsDNA)) with the single chain surfactant dodecyltrimethylammonium (DTA). In particular, we used as counter-ions of this surfactant the hydrogen sulfate and trifluoromethane sulfonate anions and the two halides, chloride and bromide. Effects on the morphology of the particles obtained, the encapsulation of DNA and its release, as well as the haemocompatibility of these particles, are presented, using the counter-ion structure and the DNA conformation as controlling parameters. Analysis of the data indicates that the degree of counter-ion dissociation from the surfactant micelles and the polar/hydrophobic character of the counter-ion are important parameters in the final properties of the particles. The stronger interaction with amphiphiles for ssDNA than for dsDNA suggests the important role of hydrophobic interactions in DNA.

Influence of ohmic heating on the flow field in thin-layer electrodeposition

In thin-layer electrodeposition the dissipated electrical energy leads to a substantial heating of the ion solution. We measured the resulting temperature field by means of an infrared camera. The properties of the temperature field correspond closely with the development of the concentration field. In particular, we find that the thermal gradients at the electrodes act similar to a weak additional driving force to the convection rolls driven by concentration gradients.

Mineral inventory of continuously erupting basaltic andesites at Arenal volcano, Costa Rica: implications for interpreting monotonous, crystal-rich, mafic arc stratigraphies

Except for the first 2 years since July 29, 1968, Arenal volcano has continuously erupted compositionally monotonous and phenocryst-rich (similar to35%) basaltic andesites composed of plagioclase (plag), orthopyroxene (opx), clinopyroxene (cpx), spinel olivine. Detailed textural and compositional analyses of phenocrysts, mineral inclusions, and microlites reveal comparable complexities in any given sample and identify mineral components that require a minimum of four crystallization environments. We suggest three distinct crystallization environments crystallized low Mg# (<78) silicate phases from andesitic magma but at different physical conditions, such as variable pressure of crystallization and water conditions. The dominant environment, i.e., the one which accounts for the majority of minerals and overprinted all other assemblages near rims of phenocrysts, cocrystallized clinopyroxene (Mg# similar to71-78), orthopyroxene (Mg# similar to71-78), titanomagnetite and plagioclase (An(60) to An(85)). The second environment cocrystallized clinopyroxene (Mg# 71-78), olivine (<Fo(78)), titanomagnetite, and very high An (similar to90) plagioclase, while the third cocrystallized clinopyroxene (Mg# 71-78) with high (>7) Al/Ti and high (>4 wt.%) Al2O3, titanomagnetite with considerable Al2O3 (10-18 wt.%) and possibly olivine but appears to lack plagioclase. A fourth crystallization environment is characterized by clinopyroxene (e.g., Mg#=similar to78-85; Cr2O3=0.15-0.7 wt.%), Al-, Cr-rich spinel olivine (similar toFo(80)), and in some circumstances high-An (>80) plagioclase. This assemblage seems to record mafic inputs into the Arenal system and crystallization at high to low pressures. Single crystals cannot be completely classified as xenocrysts, antecrysts (cognate crystals), or phenocrysts, because they often contain different parts each representing a different crystallization environment and thus belong to different categories. Bulk compositions are mostly too mafic to have crystallized the bulk of ferromagnesian minerals and thus likely do not represent liquid compositions. On the other hand, they are the cumulative products of multiple mixing events assembling melts and minerals from a variety of sources. The driving force for this multistage mixing evolution to generate erupting basaltic andesites is thought to be the ascent of mafic magma from lower crustal levels to subvolcanic depths which at the same time may also go through compositional modification by fractionation and assimilation of country rocks. Thus, mafic magmas become basaltic andesite through mixing, fractionation and assimilation by the time they arrive at subvolcanic depths. We infer new increments of basaltic andesite are supplied nearly continuously to the subvolcanic reservoir concurrently to the current eruption and that these new increments are blended into the residing, subvolcanic magma. Thus, the compositional monotony is mostly the product of repetitious production of very similar basaltic andesite. Furthermore, we propose that this quasi-constant supply of small increments of magma is the fundamental cause for small-scale, decade-long continuous volcanic activity; that is, the current eruption of Arenal is flux-controlled by inputs of mantle magmas. (C) 2004 Elsevier B.V. All rights reserved.

ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1.

Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine protease activating ENaC at the cell surface, fully restored basal AFC and the stimulation by beta(2)-agonists. Finally, acute volume-overload increased alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium and water transport and in mouse lung fluid balance.

Hypoxia-induced inhibition of epithelial Na(+) channels in the lung. Role of Nedd4-2 and the ubiquitin-proteasome pathway.

Transepithelial sodium transport via alveolar epithelial Na(+) channels (ENaC) and Na(+),K(+)-ATPase constitutes the driving force for removal of alveolar edema fluid. Alveolar hypoxia associated with pulmonary edema may impair ENaC activity and alveolar Na(+) absorption through a decrease of ENaC subunit expression at the apical membrane of alveolar epithelial cells (AECs). Here, we investigated the mechanism(s) involved in this process in vivo in the β-Liddle mouse strain mice carrying a truncation of β-ENaC C-terminus abolishing the interaction between β-ENaC and the ubiquitin protein-ligase Nedd4-2 that targets the channel for endocytosis and degradation and in vitro in rat AECs. Hypoxia (8% O2 for 24 h) reduced amiloride-sensitive alveolar fluid clearance by 69% in wild-type mice but had no effect in homozygous mutated β-Liddle littermates. In vitro, acute exposure of AECs to hypoxia (0.5-3% O2 for 1-6 h) rapidly decreased transepithelial Na(+) transport as assessed by equivalent short-circuit current Ieq and the amiloride-sensitive component of Na(+) current across the apical membrane, reflecting ENaC activity. Hypoxia induced a decrease of ENaC subunit expression in the apical membrane of AECs with no change in intracellular expression and induced a 2-fold increase in α-ENaC polyubiquitination. Hypoxic inhibition of amiloride-sensitive Ieq was fully prevented by preincubation with the proteasome inhibitors MG132 and lactacystin or with the antioxidant N-acetyl-cysteine. Our data strongly suggest that Nedd4-2-mediated ubiquitination of ENaC leading to endocytosis and degradation of apical Na(+) channels is a key feature of hypoxia-induced inhibition of transepithelial alveolar Na(+) transport.

Programming of marginal zone B-cell fate by basic Kruppel-like factor (BKLF/KLF3).

Splenic marginal zone (MZ) B cells are a lineage distinct from follicular and peritoneal B1 B cells. They are located next to the marginal sinus where blood is released. Here they pick up antigens and shuttle the load onto follicular dendritic cells inside the follicle. On activation, MZ B cells rapidly differentiate into plasmablasts secreting antibodies, thereby mediating humoral immune responses against blood-borne type 2 T-independent antigens. As Krüppel-like factors are implicated in cell differentiation/function in various tissues, we studied the function of basic Krüppel-like factor (BKLF/KLF3) in B cells. Whereas B-cell development in the bone marrow of KLF3-transgenic mice was unaffected, MZ B-cell numbers in spleen were increased considerably. As revealed in chimeric mice, this occurred cell autonomously, increasing both MZ and peritoneal B1 B-cell subsets. Comparing KLF3-transgenic and nontransgenic follicular B cells by RNA-microarray revealed that KLF3 regulates a subset of genes that was similarly up-regulated/down-regulated on normal MZ B-cell differentiation. Indeed, KLF3 expression overcame the lack of MZ B cells caused by different genetic alterations, such as CD19-deficiency or blockade of B-cell activating factor-receptor signaling, indicating that KLF3 may complement alternative nuclear factor-κB signaling. Thus, KLF3 is a driving force toward MZ B-cell maturation.

Zinc adsorption in highly weathered soils

The objective of this work was to assess the effects of pH and ionic strength upon zinc adsorption, in three highly weathered variable charge soils. Adsorption isotherms were elaborated from batch adsorption experiments, with increasing Zn concentrations (0-80 mg L-1), and adsorption envelopes were constructed through soil samples reactions with 0.01, 0.1 and 1 mol L-1 Ca(NO3)2 solutions containing 5 mg L-1 of Zn, with an increasing pH value from 3 to 8. Driving force of reaction was quantified by Gibbs free energy and separation factor. Isotherms were C-, H- and L-type and experimental results were fitted to nonlinear Langmuir model. Maximum adsorption ranged from 59-810 mg kg-1, and Zn affinity was greater in subsoil (0.13-0.81 L kg-1) than in the topsoil samples (0.01-0.34 L kg-1). Zinc adsorption was favorable and spontaneous, and showed sharply increase (20-90%) in the 4-6 pH range. No effect of ionic strength was observed at pH values below 5, because specific adsorption mechanisms predominated in the 3-5 pH range. Above pH 5, and in subsoil samples, Zn was adsorbed by electrostatic mechanisms, since ionic strength effect was observed. Despite depth and ionic strength effects, Zn adsorption depends mainly on the pH.

Mitochondrial fatty acid oxidation in obesity

Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders.

Entropic stochastic resonance

We present a novel scheme for the appearance of stochastic resonance when the dynamics of a Brownian particle takes place in a confined medium. The presence of uneven boundaries, giving rise to an entropic contribution to the potential, may upon application of a periodic driving force result in an increase of the spectral amplification at an optimum value of the ambient noise level. The entropic stochastic resonance, characteristic of small-scale systems, may constitute a useful mechanism for the manipulation and control of single molecules and nanodevices.

Structural macro factors and the affine term structure of interest rates

This work consists of three essays investigating the ability of structural macroeconomic models to price zero coupon U.S. government bonds. 1. A small scale 3 factor DSGE model implying constant term premium is able to provide reasonable a fit for the term structure only at the expense of the persistence parameters of the structural shocks. The test of the structural model against one that has constant but unrestricted prices of risk parameters shows that the exogenous prices of risk-model is only weakly preferred. We provide an MLE based variance-covariance matrix of the Metropolis Proposal Density that improves convergence speeds in MCMC chains. 2. Affine in observable macro-variables, prices of risk specification is excessively flexible and provides term-structure fit without significantly altering the structural parameters. The exogenous component of the SDF is separating the macro part of the model from the term structure and the good term structure fit has as a driving force an extremely volatile SDF and an implied average short rate that is inexplicable. We conclude that the no arbitrage restrictions do not suffice to temper the SDF, thus there is need for more restrictions. We introduce a penalty-function methodology that proves useful in showing that affine prices of risk specifications are able to reconcile stable macro-dynamics with good term structure fit and a plausible SDF. 3. The level factor is reproduced most importantly by the preference shock to which it is strongly and positively related but technology and monetary shocks, with negative loadings, are also contributing to its replication. The slope factor is only related to the monetary policy shocks and it is poorly explained. We find that there are gains in in- and out-of-sample forecast of consumption and inflation if term structure information is used in a time varying hybrid prices of risk setting. In-sample yield forecast are better in models with non-stationary shocks for the period 1982-1988. After this period, time varying market price of risk models provide better in-sample forecasts. For the period 2005-2008, out of sample forecast of consumption and inflation are better if term structure information is incorporated in the DSGE model but yields are better forecasted by a pure macro DSGE model.

IAMG - Asociación Internacional para las Geociencias Matemáticas

We introduce the International Association for Mathematical Geosciences (IAMG) from its origins to the present and summarize the means by which is fulfilling its mission. The IAMG was set up in Prague in 1968 with the intention of “promoting throughout the world the advancement of mathematics, statistics and informatics in the Geosciences”. It is a non-profit organisation that includes among its members researchers, teachers, professionals and students dedicated to mathematical and statistical Applications in all branches of the earth sciences. The IAMG publishes three major journals and a newsletter and organises a yearly conference, whist at the same time supporting many others. It bestows 4 biannual prizes that recognise outstanding achievements in its field, organises a distinguished lecturer series, and encourages Young researchers by providing Student research and travel funds and promoting Student societies. The IAMG celebrated its 40tn anniversary in Oslo, Norway, in 2008 and continues to be a venue for a vast array of researchers in this broad field by providing a common driving force for their activities

Self-similar community structure in a network of human interactions

We propose a procedure for analyzing and characterizing complex networks. We apply this to the social network as constructed from email communications within a medium sized university with about 1700 employees. Email networks provide an accurate and nonintrusive description of the flow of information within human organizations. Our results reveal the self-organization of the network into a state where the distribution of community sizes is self-similar. This suggests that a universal mechanism, responsible for emergence of scaling in other self-organized complex systems, as, for instance, river networks, could also be the underlying driving force in the formation and evolution of social networks.

Offering planning with support of roadmapping in project business

Tämän tutkielman tavoitteena on tutkia kuinka roadmapping-tekniikkaa voidaan käyttää tarjonnan suunnittelun tukena uusien tuotteiden valmistamisen yhteydessä. Työ koostuu teoreettisesta ja käytännönläheisestä osasta. Teoreettinen runko on luotu selventämään kuinka tämän hetkisen tutkimus- ja kehitys projektit lopulta muodostavat tulevaisuuden tarjoaman. Menestyksekkään tuotetarjoaman luominen vaatii, sekä uusien teknologioiden kehittämistä, että markkinoilla olevien asiakkaiden tarpeiden ymmärtämistä. Asiakassuuntaisten tuotteiden kehittäminen vaatii toimintaympäristöstä ja asiakasrajapinnasta tulevien signaalien tunnistamista ja niiden ohjaamista tuote- ja teknologia platformeille. Strategia luodaan tukemaan päätöksentekoa prosessin eri vaiheissa. Yrityskohtainen osio koostuu analyysistä, joka on tehty teetetyn kyselyn ja haas-tattelujen pohjalta. Osana analyysia ovat Major project-yksikön tämänhetkinen tarjonnansuunnitteluprosessi, strategian soveltaminen, informaation kerääminen ja priorisointi, portfolionhallinta ja roadmap-tekniikan käyttö. Ratkaisussa on esitet-ty tarjonnan suunnitteluprosessi ja siihen liittyvät kriittiset komponentit. Roadmapping-tekniikkaaon luotu yhdistämään toimintaympäristö, tuotteet ja teknologia toisiinsa. Toimintaympäristö ja tuotteet on yhdistetty myös linked-grids-tekniikan avulla.

Strategisten investointienhallinta ryhmäpäätöksenteon tukisysteemien avulla

Tutkielman tavoitteena on kehittää prosessi yrityksen strategisten investointien hal-lintaan siten, että yrityksen strateginen arkkitehtuuri mukailee dynaamisten mark-kinoiden jatkuvasti muuttuvia kriittisiä menestystekijöitä. Tutkielma tarjoaa ratkai-sun strategisten investointien kohtaamaan epävarmuuteen, kompleksisuuteen ja si-säisiin konflikteihin luomalla dynaamisiin kyvykkyyksiin perustuvan prosessin, joka toteutetaan ryhmäpäätöksenteon tukisysteemien avulla asiantuntijatietoa hyö-dyntäen. Yrityksen strateginen arkkitehtuuri on mahdollista mallintaa skenaariopohjaisen strategiakartan eli kyvykkyyskartan avulla. Kyvykkyyskarttaan sisällytetyt QFD- ja AHP-mallit mahdollistavat strategisten investointien arvottamisen markkinoiden kriittisten menestystekijöiden suhteen. Dynaamisiin kyvykkyyksiin perustuvat lead user- ja skenaariosuunnitteluvaiheet mahdollistavat puolestaan joustavan investoin-tistrategian luonnin. Tutkielma osoittaa dynaamisia kyvykkyyksiä ja ryhmäpäätök-senteon tukisysteemejä hyödyntävän strategisten investointien hallintaprosessin tarjoavan ratkaisun strategisien investointipäätösten kohtaamiin haasteisiin.Ky-vykkyyskarttaan pohjautuvan strategisen arkkitehtuurin optimointimallin katsottiin olevan realistinen ja uskottava ja korostavan investointien strategisia vaikutuksia.

GPS-paikkatiedonliittäminen matkapuhelinpalveluihin

2000-luvun vaihteessa paikkatietoa hyödyntävistä matkapuhelinpalveluista odotettiin muodostuvan eräs merkittävimmistä kilpailuvalteista eri matkapuhelinoperaattoreiden välillä. Kiinnostusta paikkatietoa hyödyntäviin palveluihin lisäsi kaupallisten sovellusten lisäksi Yhdysvaltojen liittovaltioiden liikenneministeriön säätämä laki, joka velvoittaa paikantamaan yleiseen hätänumeroon soitetut puhelut. Erityisesti laite- ja verkkotoimittajat odottivat tämänluovan heille uusia markkinoita. Markkinoille tuli useita kilpailevia menetelmiä, joilla matkapuhelimia voitiin paikantaa. Suurin osa näistä menetelmistä hyödynsi GSM-verkon signalointia paikannuksen tekemiseen. Samaan aikaan kohonnut matkapuhelinten suorituskyky mahdollisti GPS-vastaanottimien integroinnin matkapuhelimiin ja ensimmäiset tällaiset matkapuhelimet ilmestyivät markkinoille. Matkapuhelinten paikantamiseen liittyvä standardointi on melko hajanaista. ETSI on standardoinut joukon erilaisia menetelmiä, joilla matkapuhelin paikkatieto voidaan selvittää. Nämä standardit eivät kuitenkaan määrittele sitä, kuinka paikkatieto siirretään sitä hyödyntävien palveluiden käyttöön. Paikkatiedonsiirtämiseen ja esittämiseen liittyvässä standardoinnissa eri laite- ja ohjelmistovalmistajat ovat tehneet liittoutumia keskenään ja esitelleet keskenään kilpailevia standardeja ja suosituksia. Tälläkään osa-alueella mikään liittoutuma ei ole saavuttanut määräävää markkina-asemaa. Tässä työssä suunniteltiin ja toteutettiin järjestelmä, jonka avulla voidaan paikantaa sellaisia GSM-päätelaitteita, joihin on integroitu GPS-vastaanotin. Toteutettu järjestelmä liitettiin uudeksi paikannusmenetelmäksi solupaikannuksen rinnalle Sonera Pointer paikannusjärjestelmään. Työn aikana testattiin joukko markkinoilla olleita GSM-puhelimia, joihin oli integroitu GPS-vastaanotin. Matkapuhelinten testauksessa erityinen huomio kiinnittyi siihen, kuinka GPS-paikkatieto saadaan siirrettyä matkapuhelimesta verkossa sijaitsevien sovellusten käyttöön. Toteutetun järjestelmän suunnittelussa täkein lähtökohta oli järjestelmän joustavuus. Standardien hajanaisuus ja osittainen puuttuminen aiheuttivat sen, että järjestelmästä oli tehtävä mahdollisimman helposti laajennettava. Toinen merkittävä suunnitteluun vaikuttanut tekijä oli operaattoririippumattomuus, koska Sonera Pointer järjestelmää oli tarkoitus myydä myös muille matkapuhelinoperaattoreille.