Affibody molecules: Engineered proteins for therapeutic, diagnostic and biotechnological applications

AbstractAffibody molecules are a class of engineered affinity proteins with proven potential for therapeutic, diagnostic and biotechnological applications. Affibody molecules are small (6.5kDa) single domain proteins that can be isolated for high affinity and specificity to any given protein target. Fifteen years after its discovery, the Affibody technology is gaining use in many groups as a tool for creating molecular specificity wherever a small, engineering compatible tool is warranted. Here we summarize recent results using this technology, propose an Affibody nomenclature and give an overview of different HER2-specific Affibody molecules. Cumulative evidence suggests that the three helical scaffold domain used as basis for these molecules is highly suited to create a molecular affinity handle for vastly different applications

Elemental bio-imaging of thorium, uranium, and plutonium in tissues from occupationally exposed former nuclear workers

Internal exposure from naturally occurring radionuclides (including the inhaled long-lived actinides 232Th and 238U) is a component of the ubiquitous background radiation dose (National Council on Radiation Protection and Measurements. Ionizing radiation exposure of the population of the United States; NCRP Report No. 160; NCRP: Bethesda, MD, 2009). It is of interest to compare the concentration distribution of these natural ?-emitters in the lungs and respiratory lymph nodes with those resulting from occupational exposure, including exposure to anthropogenic plutonium and depleted and enriched uranium. This study examines the application of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantifying and visualizing the mass distribution of uranium and thorium isotopes from both occupational and natural background exposure in human respiratory tissues and, for the first time, extends this application to the direct imaging of plutonium isotopes. Sections of lymphatic and lung tissues taken from deceased former nuclear workers with a known history of occupational exposure to specific actinide elements (uranium, plutonium, or americium) were analyzed by LA-ICPMS. Using a previously developed LA-ICPMS protocol for elemental bio-imaging of trace elements in human tissue and a new software tool, we generated images of thorium (232Th), uranium (235U and 238U), and plutonium (239Pu and 240Pu) mass distributions in sections of tissue. We used a laboratory-produced matrix-matched standard to quantify the 232Th, 235U, and 238U concentrations. The plutonium isotopes 239Pu and 240Pu were detected by LA-ICPMS in 65 ?m diameter localized regions of both a paratracheal lymph node and a sample of lung tissue from a person who was occupationally exposed to refractory plutonium (plutonium dioxide). The average (overall) 239Pu concentration in the lymph node was 39.2 ng/g, measured by high purity germanium (HPGe) ?-spectrometry (Lynch, T. P.; Tolmachev, S. Y.; James, A. C. Radiat. Prot. Dosim. 2009, 134, 94?101). Localized mass concentrations of thorium (232Th) and uranium (238U) in lymph node tissue from a person not occupationally exposed to these elements (chronic natural background inhalation exposure) ranged up to 400 and 375 ng/g, respectively. In lung samples of occupationally nonexposed to thorium and uranium workers, 232Th and 238U concentrations ranged up to 200 and 170 ng/g, respectively. In a person occupationally exposed to air-oxidized uranium metal (Adley, F. E.; Gill, W. E.; Scott, R. H. Study of atmospheric contaminiation in the melt plant buiding. HW-23352(Rev.); United States Atomic Energy Commission: Oakridge, TN, 1952, p 1?97), the maximum 235U and 238U isotopic mass concentrations in a lymph node, measured at higher resolution (with a 30 ?m laser spot diameter), were 70 and 8500 ng/g, respectively. The ratio of these simultaneously measured mass concentrations signifies natural uranium. The current technique was not sufficiently sensitive, even with a 65 ?m laser spot diameter, to detect 241Am (at an overall tissue concentration of 0.024 ng/g, i.e., 3 Bq/g). © 2010 American Chemical Society

ПРИНЦИП ВЗАИМНОСТИ ДЛЯ НЕЛИНЕЙНОЙ АНИЗОТРОПНОЙ СРЕДЫ БЕЗ ГИСТЕРЕЗИСА: ТЕОРИЯ И ПРАКТИКА ПРИМЕНЕНИЯ

The construction of the correct vector material equations for nonlinear anisotropic soft magnetic materials remains one of the main reserves for increasing the accuracy of mathematical models in solving magnetostatic problems in the field formulation. The aim of the work is to establish asymptotic expressions for the reciprocity principle, which is a fundamental property of reversible magnetization processes of nonlinear anisotropic media, and to use the obtained results to optimize the computational process when constructing the vector magnetization characteristic and differential permeability tensor. The potentiality property of the magnetic flux density vector B in H-space is used. The main result of the paper is an illustration, using concrete examples, of an alternative method for calculating vector magnetization characteristics for one of the orthogonal families. In order to eliminate the instrumental error and ensure maximum accuracy and reliability of the obtained results, the exact characteristics for the components of the vector magnetization characteristic obtained by differentiating a special analytical expression for the potential were used as initial ones. The principle of reciprocity, by virtue of its universal nature, makes a significant contribution to the theory of nonlinear anisotropic media in the hysteresis-free approximation. Asymptotic expressions for the reciprocity principle are obtained for the first time. The performed computational experiments on the construction of vector characteristics based on the known magnetization characteristics in one of the directions confirm almost complete coincidence with the exact values obtained analytically. The use of asymptotic expressions for the reciprocity principle not only greatly simplifies computational processes for determining the orthogonal magnetization characteristics, but also implements the calculation of differential permeability tensors for arbitrary field values. The proposed method can be implemented in applications for calculating the magnetic field in devices with nonlinear anisotropic magnetically soft materials, primarily with cold rolled sheet electrical steels, which are most used in electrical engineering.Рассмотрены теоретические и практические аспекты построения векторных материальных уравнений нелинейных анизотропных сред. Показано, что используемые методы учета магнитных свойств даже в безгистерезисном приближении не всегда удовлетворяют требованиям полноты и математической строгости. Подтверждена эффективность энергетического подхода к построению векторных характеристик магнитного состояния таких сред. Особое внимание уделено принципу взаимности как фундаментальному свойству обратимых процессов намагничивания. Установлены новые асимптотические выражения для принципа взаимности и на численных примерах показана их эффективность при построении векторной модели магнитной среды без использования энергетического потенциала.

ПРИНЦИП ВЗАИМНОСТИ ДЛЯ НЕЛИНЕЙНОЙ АНИЗОТРОПНОЙ СРЕДЫ БЕЗ ГИСТЕРЕЗИСА: ТЕОРИЯ И ПРАКТИКА ПРИМЕНЕНИЯ

The construction of the correct vector material equations for nonlinear anisotropic soft magnetic materials remains one of the main reserves for increasing the accuracy of mathematical models in solving magnetostatic problems in the field formulation. The aim of the work is to establish asymptotic expressions for the reciprocity principle, which is a fundamental property of reversible magnetization processes of nonlinear anisotropic media, and to use the obtained results to optimize the computational process when constructing the vector magnetization characteristic and differential permeability tensor. The potentiality property of the magnetic flux density vector B in H-space is used. The main result of the paper is an illustration, using concrete examples, of an alternative method for calculating vector magnetization characteristics for one of the orthogonal families. In order to eliminate the instrumental error and ensure maximum accuracy and reliability of the obtained results, the exact characteristics for the components of the vector magnetization characteristic obtained by differentiating a special analytical expression for the potential were used as initial ones. The principle of reciprocity, by virtue of its universal nature, makes a significant contribution to the theory of nonlinear anisotropic media in the hysteresis-free approximation. Asymptotic expressions for the reciprocity principle are obtained for the first time. The performed computational experiments on the construction of vector characteristics based on the known magnetization characteristics in one of the directions confirm almost complete coincidence with the exact values obtained analytically. The use of asymptotic expressions for the reciprocity principle not only greatly simplifies computational processes for determining the orthogonal magnetization characteristics, but also implements the calculation of differential permeability tensors for arbitrary field values. The proposed method can be implemented in applications for calculating the magnetic field in devices with nonlinear anisotropic magnetically soft materials, primarily with cold rolled sheet electrical steels, which are most used in electrical engineering.Рассмотрены теоретические и практические аспекты построения векторных материальных уравнений нелинейных анизотропных сред. Показано, что используемые методы учета магнитных свойств даже в безгистерезисном приближении не всегда удовлетворяют требованиям полноты и математической строгости. Подтверждена эффективность энергетического подхода к построению векторных характеристик магнитного состояния таких сред. Особое внимание уделено принципу взаимности как фундаментальному свойству обратимых процессов намагничивания. Установлены новые асимптотические выражения для принципа взаимности и на численных примерах показана их эффективность при построении векторной модели магнитной среды без использования энергетического потенциала.

Synthesis and reactivity of 5-polyfluoroalkyl-5-deazaalloxazines

Reaction of 6-arylamino-1,3-dialkyluracils with anhydrides of polyfluorocarboxylic acids in the presence of pyridine and subsequent cyclization with concentrated H2SO4 gave the corresponding 1,3-dialkyl-5-(polyfluoroalkyl)pyrimido[4,5-b]quinoline-2,4(1H,3H)-diones (5-polyfluoroalkyl-5-deazaalloxazines). The reactivity of these compounds towards nucleophilic reagents, such as sodium cyanoborohydride, acetophenone, nitromethane, potassium cyanide, indole and p-thiocresol, as well as Suzuki and Sonogashira couplings are described. The nucleophilic addition takes place at the 5-position of the 5-deazaalloxazine system and is in many cases irreversible to give 5,10-dihydropyrimido[4,5-b]quinoline-2,4(1H,3H)-dione derivatives in good to excellent yields.© 2013 The Royal Society of Chemistry

influence of specific intermolecular interactions on the thermal and dielectric properties of bulk polymers atomistic molecular dynamics simulations of nylon 6

Specific intermolecular interactions, in particular H-bonding, have a strong influence on the structural, thermal and relaxation characteristics of polymers. We report here the results of molecular dynamics simulations of Nylon 6 which provides an excellent example for the investigation of such an influence. To demonstrate the effect of proper accounting for H-bonding on bulk polymer properties, the AMBER99sb force field is used with two different parametrization approaches leading to two different sets of partial atomic charges. The simulations allowed the study of the thermal and dielectric properties in a wide range of temperatures and cooling rates. The feasibility of the use of the three methods for the estimation of the glass transition temperature not only from the temperature dependence of structural characteristics such as density, but also by using the electrostatic energy and dielectric constant is demonstrated. The values of glass transition temperatures obtained at different cooling rates are practically the same for the three methods. By proper accounting for partial charges in the simulations, a reasonable agreement between the results of our simulations and experimental data for the density, thermal expansion coefficient, static dielectric constant and activation energy of γ and β relaxations is obtained demonstrating the validity of the modeling approach reported

All-optical dc nanotesla magnetometry using silicon vacancy fine structure in isotopically purified silicon carbide

We uncover the fine structure of a silicon vacancy in isotopically purified silicon carbide (4H-$^{28}$SiC) and find extra terms in the spin Hamiltonian, originated from the trigonal pyramidal symmetry of this spin-3/2 color center. These terms give rise to additional spin transitions, which are otherwise forbidden, and lead to a level anticrossing in an external magnetic field. We observe a sharp variation of the photoluminescence intensity in the vicinity of this level anticrossing, which can be used for a purely all-optical sensing of the magnetic field. We achieve dc magnetic field sensitivity of 87 nT Hz$^{-1/2}$ within a volume of $3 \times 10^{-7}$ mm$^{3}$ at room temperature and demonstrate that this contactless method is robust at high temperatures up to at least 500 K. As our approach does not require application of radiofrequency fields, it is scalable to much larger volumes. For an optimized light-trapping waveguide of 3 mm$^{3}$ the projection noise limit is below 100 fT Hz$^{-1/2}$.Comment: 12 pages, 6 figures; additional experimental data and an extended theoretical analysis are added in the second versio