Handling deviating control values in concentration-response curves

In cell biology, pharmacology and toxicology dose-response and concentration-response curves are frequently fitted to data with statistical methods. Such fits are used to derive quantitative measures (e.g. EC$$_{20}$$ 20 values) describing the relationship between the concentration of a compound or the strength of an intervention applied to cells and its effect on viability or function of these cells. Often, a reference, called negative control (or solvent control), is used to normalize the data. The negative control data sometimes deviate from the values measured for low (ineffective) test compound concentrations. In such cases, normalization of the data with respect to control values leads to biased estimates of the parameters of the concentration-response curve. Low quality estimates of effective concentrations can be the consequence. In a literature study, we found that this problem occurs in a large percentage of toxicological publications. We propose different strategies to tackle the problem, including complete omission of the controls. Data from a controlled simulation study indicate the best-suited problem solution for different data structure scenarios. This was further exemplified by a real concentration-response study. We provide the following recommendations how to handle deviating controls: (1) The log-logistic 4pLL model is a good default option. (2) When there are at least two concentrations in the no-effect range, low variances of the replicate measurements, and deviating controls, control values should be omitted before fitting the model. (3) When data are missing in the no-effect range, the Brain-Cousens model sometimes leads to better results than the default model.

On the Influence of Cross-Section and Reinforcement of Reinforced Concrete Constructions on the Concentration of Coarse Aggregate in Concrete with Frame Structure

Concretes with frame structure produced by using the technology of separate concreting by immersing a coarse aggregate in a low-viscosity mortar matrix due to an increased concentration of coarse aggregate have an increased E-modulus, reduced creep coefficient and cement volume in concrete compared to traditional vibrational compaction concretes. Production concrete using separate concreting technology by immersing a coarse aggregate in a mortar matrix with low-viscosity allows to obtain a frame structure of concrete with a concentration of coarse aggregate up to 0.7 when a voidness of coarse aggregate is equal 0.28. The real concentration of coarse aggregate in a concrete structure depends on the particle size of the coarse aggregate, the cross-section dimensions of the structure, and the reinforcement coefficient. The influence of geometric dimensions and the coefficient of reinforcement on the concentration of coarse aggregate in the concrete with frame structure is studied. The concentration of coarse aggregate decreases with the growth of the S/V modulus (S – area, m2, V – volume, m3) and the reinforcement coefficient, but the decrease in the E-modulus does not exceed 5%. Conclusion: regardless of the type of construction and reinforcement, the concrete of the frame structure must have a sufficiently high uniformity of deformation properties.

Nutraceutical Supplements in the Thyroid Setting: Health Benefits beyond Basic Nutrition

In recent years, there has been a growing interest in nutraceuticals, which may be considered as an efficient, preventive, and therapeutic tool in facing different pathological conditions, including thyroid diseases. Although iodine remains the major nutrient required for the functioning of the thyroid gland, other dietary components play important roles in clinical thyroidology—these include selenium, l-carnitine, myo-inositol, melatonin, and resveratrol—some of which have antioxidant properties. The main concern regarding the appropriate and effective use of nutraceuticals in prevention and treatment is due to the lack of clinical data supporting their efficacy. Another limitation is the discrepancy between the concentration claimed by the label and the real concentration. This paper provides a detailed critical review on the health benefits, beyond basic nutrition, of some popular nutraceutical supplements, with a special focus on their effects on thyroid pathophysiology and aims to distinguish between the truths and myths surrounding the clinical use of such nutraceuticals.

Methodology for Estimating the Lifelong Exposure to PM2.5 and NO2—The Application to European Population Subgroups

Health impacts of air pollutants, especially fine particles (PM2.5) and NO2, have been documented worldwide by epidemiological studies. Most of the existing studies utilised the concentration measured at the ambient stations to represent the pollutant inhaled by individuals. However, these measurement data are in fact not able to reflect the real concentration a person is exposed to since people spend most of their time indoors and are also affected by indoor sources. The authors developed a probabilistic methodology framework to simulate the lifelong exposure to PM2.5 and NO2 simultaneously for population subgroups that are characterised by a number of indicators such as age, gender and socio-economic status. The methodology framework incorporates the methods for simulating the long-term outdoor air quality, the pollutant concentration in different micro-environments, the time-activity pattern of population subgroups and the retrospective life course trajectories. This approach was applied to the population in the EU27 countries plus Norway and Switzerland and validated with the measurement data from European multi-centre study, EXPOLIS. Results show that the annual average exposure to PM2.5 and NO2 at European level kept increasing from the 1950s to a peak between the 1980s and the 1990s and showed a decrease until 2015 due to the implementation of a series of directives. It is also revealed that the exposure to both pollutants was affected by geographical location, gender and income level. The average annual exposure over the lifetime of an 80-year-old European to PM2.5 and NO2 amounted to 23.86 (95% CI: 2.95–81.86) and 13.49 (95% CI: 1.36–43.84) µg/m3. The application of this methodology provides valuable insights and novel tools for exposure modelling and environmental studies.

Model of phosphorus diffusion in silicon for highly doped solar cell emitter layer

Purpose The purpose of this paper was the development of a model enabling precise determination of phosphorus concentration profile in the emitter layer of a silicon solar cell on the basis of diffusion doping process duration and temperature. Fick’s second law, which is fundamental for describing the diffusion process, was assumed as the basis for the model. Design/methodology/approach To establish a theoretical model of the process of phosphorus diffusion in silicon, real concentration profiles measured using the secondary ion mass spectrometry (SIMS) method were used. Samples with the phosphorus dopant source applied onto monocrystalline silicon surface were placed in the heat zone of the open quartz tube furnace, where the diffusion process took place in the temperature of 880°C-940°C. The measured real concentration profiles of these samples became template profiles for the model in development. Findings The model was developed based on phenomena described in the literature, such as the influence of the electric field of dopant ionized atoms and the influence of dopant atom concentration nearing the maximum concentration on the value of diffusion coefficient. It was proposed to divide the diffusion area into low and high dopant concentration region. Originality/value A model has been established which enabled obtaining a high level of consistency between the phosphorus concentration profile developed theoretically and the real profile measured using the SIMS method. A coefficient of diffusion of phosphorus in silicon dependent on dopant concentration was calculated. Additionally, a function describing the boundary between the low and high dopant concentration regions was determined.

GEP I: A globular cluster in the center of the dwarf spheroidal galaxy Andromeda XXV?

Looking for variable stars in the M31 dwarf spheroidal satellite Andromeda XXV (And XXV), which we have observed with the LBC at the LBT, we serendipitously discovered a clustering of stars (Gep I) of 12 arcsec in diameter, near the center of And XXV. This is one of the very few clusters known to be associated with a dwarf spheroidal galaxy. The half light radius (rh) of Gep I at the distance of And XXV corresponds to 25 pc in linear extension. Radius and absolute V (MV∼ −4.9 mag) magnitude place Gep I in the region of the MV-rh plane that seems to be forbidden to ordinary globular clusters (GCs). The seeing-limited resolution of our photometry could resolve only a few bright stars in Gep I. The CMD of these sources is compatible with an old stellar population placed at a heliocentric distance of ∼750–800 kpc, thus confirming a real concentration of old stars. The ground-based CMD of Gep I is severely incomplete. Future high resolution imaging and spectroscopy of the brightest stars will permit to disentangle the puzzle on the real nature of Gep I.

New Method for Simultaneous Determination of Ascorbic and Acetylsalicylic Acids in Effervescent Tablets

The determination of the real concentration in different pharmaceutical drugs represents a very important goal of the pharmaceutical industry. The main aim of the study was to set up a simple, cheap and rapid method in order to determine both ascorbic and acetylsalicylic acid content of effervescent tablets that could be found on the pharmaceutical market, without preliminary separation or extraction. For this purpose, a very simple and reliable clock method based on two Landolt-type systems of reactions, based on potentiometric techniques, has been developed. The method has been tested on different effervescent tablets which contain ascorbic acid and acetylsalicylic acid in different mixture ratio.

Interrelation of Hierarchy of Structures at Comparison of Linear and Cross-linked Polymer Compounds

The comparison of behavior of a linear polymer compounds and cross-linked networks are carried out. It is shown, that the correspondence between rheological behavior of a linear polymer compound and macroscopic behavior of its cross-linked analog is determined by topology of structures describing a hydrogel as qualitatively new object as well as by the type of polymer – solvent interactions. In this situation swelling degree is completely described by the Katchalsky – Lifson’s theory. Moreover it is possible to predict microscopic behavior of macromolecular chains on the base of experimental studies of macroscopic specimens of the gel. Such investigations may be carried out in direct way for organogels. When the gel is charged (polyelectrolyte effect takes place) it is necessary to make some correction. The fact is due to so called effect of concentration redistribution, which occurs when surface of the gel acts as a membrane. In such situation the concentration of low-molecular salt inside gel may be quite more low then the concentration of the salt outside specimen. Thus in the solutions of ionogenic salts real behavior of the specimen is determined not average concentration of salt, but the real concentration of salt inside of the gel. Measuring this concentration experimentally it is possible to carried out investigations of charged macromolecular chains on the base of macroscopic specimens too.

Cod Fractions - Methods of Measurement and Use in Wastewater Treatment Technology

The paper presents the results of studies concerning the designation of COD fraction in raw wastewater. The research was conducted in four municipal mechanical-biological sewage treatment plants and one industrial sewage treatment plant. The following fractions of COD were determined: non-biodegradable (inert) soluble SI, biodegradable soluble fraction SS, particulate slowly degradable XS and particulate non-biodegradable XI. The methodology for determining the COD fraction was based on the ATV-A131 guidelines and Łomotowski-Szpindor methodology. The real concentration of fractions in raw wastewater and the percentage of each fraction in total COD are different from data reported in the literature.

Evaluasi Ketidakpastian Pengukuran Multi-Unsur Dalam Mineral Zirkon Dengan Metode Analisis Aktivasi Neutron

Evaluasi analisis multi-unsur yang disertai perhitungan ketidakpastian unsur pada mineral zirkon yang berasal dari Sampit, Kalimantan Tengah dan Pulau Bangka telah dilakukan dengan metode Analisis Aktivasi Neutron (AAN). Tujuan penelitian ini adalah menentukan komposisi dan nilai ketidakpastian multi-unsur dalam mineral zirkon untuk memenuhi persyaratan ISO/IEC guide 17025-2008 yang telah diterapkan pada laboratorium AAN. Analisis menggunakan spektrometri gamma dengan detektor HPGe menghasilkan 21 unsur terdeteksi yang dibagi menjadi tiga kelompok (mayor, minor, dan kelumit). Evaluasi ketidakpastian pengukuran perlu dilakukan untuk meningkatkan kualitas dan tingkat kepercayaan hasil analisis. Hasil pengujian tidak akan bermakna tanpa disertai perhitungan ketidakpastian. Oleh karena itu, dilakukan evaluasi nilai perhitungan ketidakpastian pada hasil analisis semua unsur yang terkandung dalam mineral zirkon. Hasil analisis kuantitatif tertinggi adalah zirkonium (Zr) dengan konsentrasi 38,986% dan mempunyai nilai ketidakpastian 0,33% sehingga nilai konsentrasi nyata adalah 38,986±0,33%, dalam oksida (ZrO2) mempunyai konsentrasi 52,661±0,45%. Unsur stibium (Sb) adalah unsur yang terdeteksi paling rendah dengan nilai konsentrasi dan ketidakpastian adalah 7±0,3 μg/g sedangkan dalam oksida (Sb2O3) mempunyai konsentrasi 17±0,9 μg/g. Komposisi oksida dan bahan kimia dalam mineral pasir zirkon yang lebih signifikan berasal dari Sampit dengan kandungan ZrO2+HfO2 (53-55%), F2O3 (5-6%), TiO2 (13-14%), Al2O3 (1,5-2%) dan SiO2. Unsur Si (SiO2) tidak dapat ditentukan dengan metode AAN sebab tampang lintang Si sangat kecil. The evaluation of multi-elements analysis has been carried out with calculation of element uncertainy in the zircon mineral from Sampit (Central Kalimantan) dan Bangka has been evaluated by the Neutron Activation Analysis (NAA) method. The purpose of this research is determination of composition and value of multi-elements uncertainty in the mineral of zircon to fulfil the requirements of ISO/IEC guide 17025-2008 that applied at NAA laboratory. The result of analysis using gamma spectrometry with a HPGe detector showed of 21 detected elements, divided into three groups (major, minor, and trace). Evaluation of uncertainty estimation should be done to increase quality and confidence rate of analysis results. The result of testing are not mean without calculation of uncertainty. Therefore, it was assessed the uncertainty measurement of all elements analysis in zircon mineral. The results of quantitative analysis is Zr with the highest concentration value of 38.986% and value of uncertainty is 0.331% so that value of real concentration is 38.986 ± 0.331%. In the form of oxide (ZrO2) has concentration of 52.661±0.45%. Sb element is the lowest element detected with value of concentration and uncertainty is 7±0,3 µg/g. In the form of oxide (Sb2O3) has concentration is 17±0.9 µg/g. The oxide composition and the must important of chemicals in the zircon sand mineral more significant from Sampit which quantitative composition areZrO2+HfO2 (53-55%), F2O3 (5-6%), TiO2 (13-14%), Al2O3 (1.5-2%) and SiO2. Elements ofSi(SiO2) can not be determinedbyNAAmethodbecauseSi cross-sections is verysmall.