Antibody-antigen interactions: What is the required time to equilibrium?

The use of antibodies is widespread in many areas including in-vivo and in-vitro diagnostics, quantitative analysis in research laboratories and as therapeutic substances. Since the methods for generation of antibodies has improved and regularly results in high-affinity interactions, the standard assays used for quantification of the interaction properties should be revisited because they do not necessarily produce accurate results. Here we show that in several cases, the affinity determination of strongly binding antibodies will be inherently difficult when using standard procedures, due to impractically long incubation times. Real-time kinetic analysis is often the only realistic alternative for affinity determination

Selective Photocatalytic Reduction of CO2-to-CO in Water using a Polymeric Carbon Nitride Quantum Dot/Fe-Porphyrin Hybrid Assembly

Visible light-driven conversion of CO2 into more value-added products is a promising technology not only for diminution of CO2 emission but also for solar energy storage in the form of chemical energy. However, photocatalytic materials that can efficiently and selectively reduce CO2-to-CO in a fully aqueous solution typically involve precious metals that limit their suitability for large scale applications. Herein, a novel photocatalytic assembly is reported, consisting of polymeric carbon nitride quantum dots (CNQDs) as the visible light absorber and a Fe-porphyrin complex (Fe-p-TMA) as the catalyst for CO2-to-CO conversion. Both components were carefully selected to allow for excellent solubility in water as well as improved electronic communication through complementary electrostatic and π-π interactions. This CNQD ⋅ [Fe-p-TMA] hybrid assembly, at the optimized molar ratio, can produce CO with a turnover number (TON) exceeding 105 and selectivity ∼96 % after 10 hours of visible light irradiation (400–700 nm). It is postulated that the enhanced CO2-to-CO transformation performance is due to the convenience of a more direct charge transfer (CT) pathway between the CNQDs and [Fe-p-TMA] motif

Evaluating Complementary Therapies for Canine Osteoarthritis—Part II: A Homeopathic Combination Preparation (Zeel®)

A homeopathic combination preparation (HCP) for canine osteoarthritic pain was evaluated in a randomized, double-controlled and double-blinded clinical trial. Forty-four dogs with osteoarthritis (OA) that were randomly allocated into one of three groups completed the study. All dogs were fed test products or placebo for 8 weeks. The dogs were evaluated at the clinic four times, with 4-week intervals. Six different variables were assessed: veterinary-assessed mobility, two force plate variables, an owner-evaluated chronic pain index and pain and locomotion visual analogue scales (VASs). Intake of extra non-steroidal anti-inflammatory drugs was also evaluated. A Chi-squared test and a Mann–Whitney test were used to determine significant improvement between groups. When changed into dichotomous responses of ‘improved’ or ‘not improved’ three out of the six variables showed a significant difference (P = 0.016, P = 0.008, P = 0.039) in improved dogs per group, between the HCP group and the placebo group. The odds ratios were over one for the same variables. As extent of improvement in the variables from start to end of treatment, the HCP product was significantly more improved in four (P = 0.015, P = 0.028, P = 0.049, P = 0.020) of the six variables, compared with the placebo. Our results indicated that the HCP Zeel® was beneficial in alleviating chronic orthopedic pain in dogs although it was not as effective as carprofen

A Secure Semi-Field System for the Study of Aedes aegypti

Novel vector control strategies require validation in the field before they can be widely accepted. Semi-field system (SFS) containment facilities are an intermediate step between laboratory and field trials that offer a safe, controlled environment that replicates field conditions. We developed a SFS laboratory and cage complex that simulates an urban house and yard, which is the primary habitat for Aedes aegypti, the mosquito vector of dengue in Cairns Australia. The SFS consists of a Quarantine Insectary Level-2 (QIC-2) laboratory, containing 3 constant temperature rooms, that is connected to two QIS-2 cages for housing released mosquitoes. Each cage contains the understory of a “Queenslander” timber house and associated yard. An automated air conditioning system keeps temperature and humidity to within 1°C and 5% RH of ambient conditions, respectively. Survival of released A. aegypti was high, especially for females. We are currently using the SFS to investigate the invasion of strains of Wolbachia within populations of A. aegypti

Electrical generation and absorption of phonons in carbon nanotubes

The interplay between discrete vibrational and electronic degrees of freedom directly influences the chemical and physical properties of molecular systems. This coupling is typically studied through optical methods such as fluorescence, absorption, and Raman spectroscopy. Molecular electronic devices provide new opportunities for exploring vibration-electronic interactions at the single molecule level. For example, electrons injected from a scanning tunneling microscope tip into a metal can excite vibrational excitations of a molecule in the gap between tip and metal. Here we show how current directly injected into a freely suspended individual single-wall carbon nanotube can be used to excite, detect, and control a specific vibrational mode of the molecule. Electrons inelastically tunneling into the nanotube cause a non-equilibrium occupation of the radial breathing mode, leading to both stimulated emission and absorption of phonons by successive electron tunneling events. We exploit this effect to measure a phonon lifetime on the order of 10 nanoseconds, corresponding to a quality factor well over 10000 for this nanomechanical oscillator.Comment: 17 pages, 4 figure

Phylogeography of Japanese encephalitis virus:genotype is associated with climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

Synthesis of α1-microglobulin in cultured rat hepatocytes is stimulated by interleukin-6, leukemia inhibitory factor, dexamethasone and retinoic acid

AbstractThe secretion or α1-microglobulin by primary cultures of rat hepatocytes was found to increase upon the addition of interleukin-6 or leukemia inhibitory factor, two mediators of acute phase response. This stimulatory effect was further enhanced by dexamethasone. α1-Microglobulin is synthesized as a precursor also containing bikunin, and the precursor protein is cleaved shortly berore secretion. Our results therefore suggest that both α1-microglobulin and bikunin are acute phase reactants in rat hepatocytes. Furthermore, we found that retinoic acid, previously shown to be involved in the regulation of cell differentiation and development, also stimulated α1-microglobulin synthesis. Only free, uncomplexed α1-microglobulin (28,000 Da) was detected in the hopatocyte media, suggesting that the complex between α1-microglobulin and α1-inhibitor 3, found in rat serum, is formed outside the hepatocyte

Effect of nitrous oxide on cisatracurium infusion demands: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Recent studies have questioned our previous understanding on the effect of nitrous oxide on muscle relaxants, since nitrous oxide has been shown to potentiate the action of bolus doses of mivacurium, rocuronium and vecuronium. This study was aimed to investigate the possible effect of nitrous oxide on the infusion requirements of cisatracurium.</p> <p>Methods</p> <p>70 ASA physical status I-III patients aged 18-75 years were enrolled in this randomized trial. The patients were undergoing elective surgery requiring general anesthesia with a duration of at least 90 minutes. Patients were randomized to receive propofol and remifentanil by target controlled infusion in combination with either a mixture of oxygen and nitrous oxide (Nitrous oxide/TIVA group) or oxygen in air (Air/TIVA group). A 0.1 mg/kg initial bolus of cisatracurium was administered before tracheal intubation, followed by a closed-loop computer controlled infusion of cisatracurium to produce and maintain a 90% neuromuscular block. Cumulative dose requirements of cisatracurium during the 90-min study period after bolus administration were measured and the asymptotic steady state rate of infusion to produce a constant 90% block was determined by applying nonlinear curve fitting to the data on the cumulative dose requirement during the study period.</p> <p>Results</p> <p>Controller performance, i.e. the ability of the controller to maintain neuromuscular block constant at the setpoint and patient characteristics were similar in both groups. The administration of nitrous oxide did not affect cisatracurium infusion requirements. The mean steady-state rates of infusion were 0.072 +/- 0.018 and 0.066 +/- 0.017 mg * kg-1 * h-1 in Air/TIVA and Nitrous oxide/TIVA groups, respectively.</p> <p>Conclusions</p> <p>Nitrous oxide does not affect the infusion requirements of cisatracurium.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT01152905; European Clinical Trials Database at <url>http://eudract.emea.eu.int/2006-006037-41</url>.</p

Randomised phase II trial of irinotecan plus cisplatin vs irinotecan, cisplatin plus etoposide repeated every 3 weeks in patients with extensive-disease small-cell lung cancer

Patients with previously untreated extensive-disease small-cell lung cancer were treated with irinotecan 60 mg m−2 on days 1 and 8 and cisplatin 60 mg m−2 on day 1 with (n=55) or without (n=54) etoposide 50 mg m−2 on days 1–3 with granulocyte colony-stimulating factor support repeated every 3 weeks for four cycles. The triplet regimen was too toxic to be considered for further studies