Current directions in DNA gel particles

A general understanding of interactions between DNA andoppositely charged compounds forms the basis for developing novelDNA-based materials, including gel particles. The association strength,which is altered by varying the chemical structure of the cationiccosolute, determines the spatial homogeneity of the gelation process,creating DNA reservoir devices and DNA matrix devices that can bedesigned to release either single- (ssDNA) or double-stranded(dsDNA) DNA. This paper reviews the preparation of DNA gelparticles using surfactants, proteins and polysaccharides. Particlemorphology, swelling/dissolution behaviour, degree of DNAentrapment and DNA release responses as a function of the nature ofthe cationic agent used are discussed. Current directions in thehaemocompatible and cytotoxic characterization of these DNA gelparticles have been also included.

Effects of math anxiety on student success in higher education

This study examines whether math anxiety and negative attitudes toward mathematics have an effect on university students" academic achievement in a methodological course forming part of their degree. A total of 193 students were presented with a math anxiety test and some questions about their enjoyment, self-confidence and motivation regarding mathematics, and their responses were assessed in relation to the grades they had obtained during continuous assessment on a course entitled"Research Design". Results showed that low performance on the course was related to math anxiety and negative attitudes toward mathematics. We suggest that these factors may affect students" performance and should therefore be taken into account in attempts to improve students" learning processes in methodological courses of this kind.

A semi-grand canonical Monte Carlo simulation model for ion binding to ionizable surfaces: proton binding of carboxylated latex particles as a case study

In this paper, we present a computer simulation study of the ion binding process at an ionizable surface using a semi-grand canonical Monte Carlo method that models the surface as a discrete distribution of charged and neutral functional groups in equilibrium with explicit ions modelled in the context of the primitive model. The parameters of the simulation model were tuned and checked by comparison with experimental titrations of carboxylated latex particles in the presence of different ionic strengths of monovalent ions. The titration of these particles was analysed by calculating the degree of dissociation of the latex functional groups vs. pH curves at different background salt concentrations. As the charge of the titrated surface changes during the simulation, a procedure to keep the electroneutrality of the system is required. Here, two approaches are used with the choice depending on the ion selected to maintain electroneutrality: counterion or coion procedures. We compare and discuss the difference between the procedures. The simulations also provided a microscopic description of the electrostatic double layer (EDL) structure as a function of p H and ionic strength. The results allow us to quantify the effect of the size of the background salt ions and of the surface functional groups on the degree of dissociation. The non-homogeneous structure of the EDL was revealed by plotting the counterion density profiles around charged and neutral surface functional groups.

Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms.

PURPOSE: In this study, we investigated the mechanisms by which temozolomide enhances radiation response in glioblastoma cells. EXPERIMENTAL DESIGN: Using a panel of four primary human glioblastoma cell lines with heterogeneous O(6)-methylguanine-DNA methyltransferase (MGMT) protein expression, normal human astrocytes, and U87 xenografts, we investigated (a) the relationship of MGMT status with efficacy of temozolomide-based chemoradiation using a panel of in vitro and in vivo assays; (b) underlying mechanisms by which temozolomide enhances radiation effect in glioblastoma cells; and (c) strategies to overcome resistance to radiation + temozolomide. RESULTS: Temozolomide enhances radiation response most effectively in glioblastomas without detectable MGMT expression. On concurrent radiation + temozolomide administration in MGMT-negative glioblastomas, there seems to be decreased double-strand DNA (dsDNA) repair capacity and enhanced dsDNA damage compared either with radiation alone or with sequentially administered temozolomide. Our data suggest that O(6)-benzylguanine can enhance the antitumor effects of concurrent radiation + temozolomide in MGMT-positive cells by enhancing apoptosis and the degree of dsDNA damage. O(6)-Benzylguanine was most effective when administered concurrently with radiation + temozolomide and had less of an effect when administered with temozolomide in the absence of radiation or when administered sequentially with radiation. Our in vivo data using U87 xenografts confirmed our in vitro findings. CONCLUSIONS: The present study shows that temozolomide enhances radiation response most effectively in MGMT-negative glioblastomas by increasing the degree of radiation-induced double-strand DNA damage. In MGMT-positive glioblastomas, depletion of MGMT by the addition of O(6)-benzylguanine significantly enhances the antitumor effect of concurrent radiation + temozolomide. These are among the first data showing mechanisms of synergy between radiation and temozolomide and the effect of MGMT.

High prevalence of major cardiovascular risk factors in first-degree relatives of individuals with familial premature coronary artery disease : the GENECARD project

Rapport de synthèse La prévalence de l'hypertension artérielle, d'une dyslipidémie, d'une obésité et d'un tabagisme est élevée chez les patients qui souffrent d' une maladie coronarienne familiale précoce (MC-FP). L? e but de cette étude fut d'investiguer la prévalence de ces facteurs de risque cardiovasculaires au sein des membres d'une famille dont un patient est affecté d'une MC-FP. Nous avons étudié 108 familles différentes dont au minimum 2 frères/soeurs ont survécu à une maladie coronarienne précoce. Cette dernière fut définie par la survenue d'un événement coronarien avant l'âge de 51 ans pour les hommes et 56 ans pour les femmes. Au total, nous avons identifié 222 patients atteints de MC-FP chez qui 158 frères/soeurs, 197 enfants et 94 époux/épouses ne souffraient pas de maladie coronarienne. Ces parents proches furent comparés à un collectif d'individus "contrôles" issus de la population générale. Les frères/soeurs non affectés avaient une prévalence plus élevée d'hypertension artérielle (49% versus 24%, p<0.001), d'hypercholestérolémie (47% versus 34%, p=0.002), d'obésité abdominale (35% versus 24%, p=0.006) et de tabagisme (39% versus 24%, p=0.001) par rapport aux individus issus de la population générale. Parmi les enfants, une prévalence plus élevée d'hypertension artérielle fut identifiée chez les femmes, et une prévalence plus élevée d'hypercholestérolémie et d'obésité abdominale dans les deux sexes par rapport aux contrôles de la population générale. Aucune différence parmi les facteurs de risque cardiovasculaire n'a été observée entre les époux/ épouses et les contrôles. Les frères/soeurs affectés et non affectés par la MC-FP ont également été comparés entre eux. La prévalence des facteurs de risque était similaire dans les 2 groupes, sauf pour le tabagisme, qui avait une prévalence plus élevée chez les frères/sueurs affectés (76% versus 39%, p=0.008). La prévalence de l'hypertension artérielle, de l'obésité, et de la dyslipidémie est également élevée chez les parents de premier degré de patients atteints de MC-FP, mais pas chez leurs époux/épouses. Ces personnes-là requièrent donc une attention médicale particulière en raison d'une vulnérabilité familiale et/ou génétique augmentée aux anomalies métaboliques athérogènes. Dans ces familles, le tabagisme pourrait être le facteur déclenchant de la MC-FP.

Double-blind comparison of indapamide with a placebo in hypertensive patients treated by practicing physicians.

The antihypertensive effect of indapamide (2.5 mg/day) was compared to that obtained with a placebo in a controlled trial carried out by 11 physicians in their private practice. Thirty-one patients with uncomplicated essential hypertension were included. After a run-in period of 3 weeks without any treatment, either indapamide (n = 16) or a placebo (n = 15) were administered for 8 weeks in double-blind fashion. Blood pressure decreased in both groups. In patients treated with indapamide, systolic pressure was significantly lower than in those given the placebo at 3 out of the 4 follow-up visits; diastolic pressure, however, was significantly lower only at the end of the trial. Both the active drug and the placebo were well tolerated. No significant change in body weight, plasma potassium and uric acid occurred during the study in either group of patients. It appears therefore that indapamide, at a dose which apparently has no major diuretic effect, may be useful for practitioners in managing patients with mild to moderate hypertension.

Double-Antiprism Central Configurations of the 3n-Body Problem

Abstract In this paper we study numerically a new type of central configurations of the 3n-body problem with equal masses which consist of three n-gons contained in three planes z = 0 and z = ±β = 0. The n-gon on z = 0 is scaled by a factor α and it is rotated by an angle of π/n with respect to the ones on z = ±β. In this kind of configurations, the masses on the planes z = 0 and z = β are at the vertices of an antiprism with bases of different size. The same occurs with the masses on z = 0 and z = −β. We call this kind of central configurations double-antiprism central configurations. We will show the existence of central configurations of this type.

Remaining rod activity mediates visual behavior in adult Rpe65-/- mice.

Purpose: C57/Bl6, Cpfl1-/- (Cone photoreceptors function loss 1; pure rod function), Gnat1alpha-/- (rod alpha-transducin; pure cone function) and Rpe65-/-;Rho-/- double knock-out mice were studied in order to distinguish the respective contributions of the different photoreceptor (PR) systems that enable light perception and mediate a visual reflex in adult Rpe65-/- mice using a simple behavioural procedure. Methods: Visual function was estimated using a rotating automatized optomotor drum covered with vertical black and white stripes at spatial frequencies of 0.025 to 0.5 cycles per degree (cpd) in both photopic and scotopic conditions. To evaluate the contribution as well as the light intensity threshold of each PR system, we tested the mouse strains with different luminances. Results: Stripe rotation elicits head movements in wild-type (WT) animals in photopic and scotopic conditions depending on the spatial frequency, whereas Cpfl1-/- mice show a reduced activity in the photopic condition and Gnat1alpha-/- mice an almost absent response in the scotopic condition. Interestingly, a robust visual response is obtained with Rpe65-/- knockout mice at 0.075 cpd and 0.1 cpd in the photopic condition. The residual rod function in the Rpe65-/- animals was demonstrated by testing Rpe65-/-;Rho-/- mice that present no response in photopic conditions. Conclusions: The optomotor test is a simple method to estimate the visual function, and to evaluate the respective contributions of rod and cone systems. Using this test, we demonstrate that in Rpe65-/- mice, devoid of functional cones and of detectable 11-cis-retinal protein, rods mimic in part the cone function by mediating vision in photopic conditions.

Effects of salbutamol on the contractile properties of human skeletal muscle before and after fatigue.

AIM: The study examined the effects of an oral acute administration of the beta2-agonist salbutamol (Sal) (6 mg) vs. placebo on muscle strength and fatigability in 12 non-asthmatic recreational male athletes in a randomized double-blind protocol. METHODS: Contractile properties of the right quadriceps muscle were measured during electrical stimulations, i.e. twitch, 1-s pulse trains at 20 (P(20) ) and 80 Hz (P(80) ) and during maximal voluntary isometric contraction (MVIC) before (PRE) and after (POST) a fatigue-producing protocol set by an electromyostimulation (30 contractions, frequency: 75 Hz, on-off ratio: 6.25-20s). In addition, the level of muscle voluntary activation was measured. RESULTS: In PRE and POST conditions, the peak torque (PT) of twitch, P(80) and MVIC were not modified by the treatment. The PT in POST P(20) was slightly, although not significantly, less affected by fatigue in Sal compared with placebo condition. Moreover, twitch half-relaxation time at PRE was smaller under Sal than under placebo (P < 0.05). No significant changes in the degree of voluntary activation were observed with Sal treatment in PRE or POST condition. CONCLUSION: Although these findings did not exclude completely an effect of Sal on peripheral factors of human skeletal muscle, oral acute administration of the beta2-agonist Sal seems to be without any relevant ergogenic effect on muscle contractility and fatigability in non-asthmatic recreational male athletes.

Wishes or Constraints? Mothers' Labour Force Participation and its Motivation in Switzerland

The aim of this article is to estimate the impact of various factors related to role conflict theory and preference theory on the reduction of women's labour force participation after their transition to parenthood. Objective and subjective dimensions of women's labour force participation are assessed. The empirical test is based on a survey of couples with children in Switzerland. Results show that compared to structural factors associated with role conflict reduction, preferences have little impact on mothers' labour force participation, but explain a good deal of their frustration if the factual situation does not correspond to their wishes. Structural factors, such as occupation, economic resources, childcare, and an urban environment, support mothers' labour force participation, whereas active networks and a home centred lifestyle preference help them to cope with frustrations.

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1 beta monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment.Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4 x 4-weekly doses of canakinumab (50 + 50 + 25 + 25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks.Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses >= 50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p <= 0.0083), and the percentage of patients experiencing >= 1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing >= 1 flare for canakinumab doses >= 50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28-0.36, p <= 0.05). The incidence of adverse events was similar across treatment groups.Conclusions Single canakinumab doses >= 50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.