Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation

CD4+ T cells proliferating in response to purified double-stranded deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HLA-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ but not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and antigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results suggest the existence of a novel mechanism of down-modulation of the CD4+ T cell function generated by lack of stimulation due to the HLA-II presenting molecules being "occupied" by dsDNA.     

2,2‐Dinitro‐1,3‐Bis‐Nitrooxy‐Propane (NPN): A New Energetic Plasticizer

A new energetic plasticizer, 2,2‐dinitro‐1,3‐bis‐nitrooxy‐propane (NPN), has been characterized. Its high oxygen balance, +12.5%, and low glass transition temperature, −81.5 °C (midpoint), makes it very attractive as an energetic plasticizer in solid propellants. The ability of NPN to lower the glass transition temperature and viscosity of uncured PolyNIMMO has been studied and compared to other energetic plasticizers, such as BDNPA/F and butyl‐NENA. NPN has a similar plasticizing effect as butyl‐NENA, both on depressing the glass transition temperature and lowering the viscosity. To increase the poor thermal stability of NPN, several conventional nitrocellulose/nitroglycerine stabilizers were evaluated. Further work is however needed to find a more effective stabilizer.     

Pneumocystis carinii pneumonia in preterm infants: report of two cases successfully diagnosed by non-bronchoscopic bronchoalveolar lavage

We present two cases of Pneumocystis carinii pneumonia in apparently immunocompetent preterm infants presenting with unexplained respiratory distress associated with a predominantly interstitial process on the chest radiograph. Definite diagnosis was promptly established on the detection of cyst forms in the lung fluid obtained by non-bronchoscopic bronchoalveolar lavage, and a favourable outcome was achieved.     

Maxsim2—Real-time interactive simulations for computer-assisted teaching of pharmacokinetics and pharmacodynamics

We developed a computer program for use in undergraduate and graduate courses in pharmacology, pharmacokinetics and pharmacodynamics. This program can also be used in environmental and toxicological studies and preclinical simulation, to facilitate communication between modeling pharmacokineticists and project leaders or other decision-makers in the pharmaceutical industry. The program simulates the drug delivery and transport by means of (I) a six-compartment physiological pharmacokinetic flow model, (II) a system of traditional compartment models, or (III) a target-mediated drug disposition system. The program also can be used to simulate instantaneous equilibria between concentration and pharmacodynamic response, or as temporal delays between concentration and response. The latter is done by means of turnover models (indirect response models). Drug absorption, distribution, and elimination are represented by differential equations, which are described by organ and tissue volumes or other volumes of distribution, blood flows, clearance terms, and tissue-to-blood partition coefficients. The user can control and adjust these parameters by means of a slider in real time. By interactively changing the parameter values and simultaneously displaying the resulting concentration–time and/or response–time profiles, users can understand the major mechanisms that govern the disposition or the pharmacological response of the drug in the organism in real time. Schedule dependence is typically seen in clinical practice with a non-linear concentration–response relationship, and is difficult to communicate except via simulations. Here, we sought to illustrate the potential advantages of this approach in teaching pharmacology, pharmacokinetics, and pharmacodynamics to undergraduate pharmacy-, veterinary-, and medical students or to project teams in drug discovery/development.     

Compliant activity rather than difficulty accelerates thought probe responsiveness and inhibits deliberate mind wandering

ABSTRACT

Mind wandering is a commonly intruding cognitive state that leads to diminished performance and increased error risk during a primary task. A controversy over whether easier or more difficult tasks increase mind wandering has led to mind wandering being proposed as two different states: deliberate and spontaneous. We hypothesise that forced engagement via persistent compliant activity may both increase responsiveness and inhibit non-instrumental activities including deliberate mind wandering. Twenty-eight healthy adults interacted with 2 pairs of stimuli, each pair having one low-interactivity version and a high-interactivity version requiring compliant activity. Mind wandering was assessed by thought probes, and subjective responses were rated using visual analogue scales. Reaction times were measured using Superlab. Compliant activity decreased the prevalence of deliberate mind wandering episodes but not of overall mind wandering. Thought probe durations were accelerated significantly by compliant activity, near-significantly by thinking on-task thoughts, and additively by the combination of both. Deliberate and spontaneous mind wandering elicited equivalent thought probe durations. We conclude that compliant activity works synergistically with lack of mind wandering to accelerate the difficult task of thought probe response but not simple reaction times. These results fit with an arousal model but not the attentional resources model.     

Latex coatings containing antifeedants: Formulation,characterization, and application for protection of conifer seedlings against pine weevil feeding

Latex-based coatings for protection of tree seedlings against pest insect feeding are evaluated with respect to surface-, mechanical-, and release properties and antifeedant activity. The latex dispersion Eudragit copolymer (EC) was used to form the coatings, 2,6-di-tert-butyl-4-methylphenol (BHT) and cis-dihydropinidine (Alk) as antifeedants, and a thickener and a alkylglucoside based nonionic surfactant were used as additives to optimize the release- and mechanical properties of coatings. Coating characterization was performed with respect to surface morphology (atomic force microscopy, AFM) and surface wetting (contact angle), as well as to mechanical (tensile stress- and tensile strain at break) properties. Surface smoothness and wettability as well as elasticity increased with addition of the surfactant. The optimized coatings were found to be elastic and water resistant at 3–6 wt.% of BHT and 3 wt.% of surfactant. BHT was released into SDS/water at very low rates. Several formulations of BHT and Alk were efficient in preventing the feeding on conifer bark by a pine insect, Hylobius abietis both in laboratory (no-choice) and in field (3 months) tests.     

Antifeedants against <Emphasis Type="Italic">Hylobius abietis</Emphasis> Pine Weevils: An Active Compound In Extract of Bark of <Emphasis Type="Italic">Tilia cordata</Emphasis> Linden

Linden (Tilia cordata) bark was shown to contain an antifeedant effective against the large pine weevil, Hylobius abietis. Soxhlet extraction of inner and outer bark resulted in an extract that showed antifeedant activity in a microfeeding assay. The extract was fractionated by chromatography on silica gel using gradient elution with solvents of increasing polarity. The content of the fractions obtained was monitored by thin layer- and gas chromatography. Fractions of similar chemical composition were merged. Two of the 17 fractions showed antifeedant activity in the microfeeding assay. Nonanoic acid was identified in both of these fractions. Subsequent testing in the microfeeding assay showed that nonanoic acid possessed strong antifeedant activity against H. abietis adults.     

Soil nitrous oxide emissions under different management practices in the semiarid region of the Argentinian Pampas

The aim of this study was to analyze the influence of different crop sequences (soybean-corn and soybean?Csoybean) and tillage systems (no tillage and reduced tillage) on nitrous oxide (N₂O) soil emissions under field conditions. The experiment was carried out in Manfredi, Córdoba province, Argentina on an Entic Haplustoll and N₂O emissions were measured in the field during a year. N₂O fluxes were low during winter, but in late spring it peaked. For fallow, N-NO₃-content was the most important variable to explain N₂O emissions. For growing period water-filled pores was the main variable explaining N₂O emissions. Nitrogen fertilization of corn crop increased N₂O-N emissions, whereas no significant differences were found due to the tillage system. Measured annual N₂O-N emissions were generally lower than those calculated using the methodology proposed by the Intergovernmental Panel on Climate Change.     

High levels of glycoalkaloids in the established swedish potato variety magnum bonum

In 1986, potentially toxic levels of the glycoalkaloids α-solanine and α-chaconine were unexpectedly found in tubers of the established Swedish consumer potato variety Magnum Bonum, leading to the imposition of a conditional sales ban on such potatoes. The combined amounts of α-solanine and α-chaconine in more than 300 commercial lots of Magnum Bonum potatoes analysed as a consequence of the ban ranged from 61 to 665 mg kg^?1 fresh weight with an average of 254 mg kg^?1. Sixty-six percent of the samples exceeded a temporary maximum residue limit of 200 mg kg^?1, 8% were above 400 mg kg^?1. Peeling did not significantly remove the glycoalkaloids in tubers with a high content. The occasional glycoalkaloid elevation was initially attributed to the unusually cold and rainy conditions during the late part of the season in 1986, but subsequent investigations have failed to confirm this hypothesis. Varietal characteristics are likely to have been involved since most other common Swedish varieties seemed to have had normal glycoalkaloid levels in 1986. There were no indications of serious or widespread adverse health effects in consumers due to the high glycoalkaloid levels, although there was circumstantial evidence that a few cases of temporary gastrointestinal disturbances were caused by consumption of Magnum Bonum potatoes with glycoalkaloid concentrations in the range 310–1000 mg kg^?1.