Functionalized azamacrocyclic compounds as Ca2+ sensitive contrast agents for MR imaging

The ability to non-invasively observe changes in Ca2+ concentration is important for neuroscience. We have therefore developed a series of gadolinium chelate complexes based on DO3A (Scheme 1), which is hypothesized to change relaxivity in magnetic resonance experiments dynamically with Ca2+ concentration. Different lengths of the phosphonate side chains are expected to lead to different binding constants of the phosphonate - gadolinium bonds. The latter property can be exploited for fine-tuning the sensitivity of the agent to calcium ion concentration

Azamacrocyclic Ca2+ Sensitive Contrast Agents for MR Imaging

As calcium plays an important role in regulating a great variety of neuronal processes, many efforts are already made to generate gadolinium complexes that can act as a calcium-sensors in MRI.1 We developed a series of the DO3A-based macrocyclic and bismacrocyclic gadolinium chelates, bearing phosphonate groups as an additional coordination sites. These complexes are hypothesized to change the MRI contrast dynamically with Ca2+ concentration. Different lengths of the phosphonate side chains are exploited for fine-tuning the sensitivity of the agent to calcium ion concentration

Smart MRI Agents Sensing Extracellular Calcium Fluctuations

Functional Magnetic Resonance Imaging (fMRI) is currently the main tool used for the study of function and dysfunction of the human brain. The current mainstay of fMRI, the so-called Blood-Oxygen-Level-Dependent (BOLD) contrast, capitalizes on the detection of changes in cerebral blood flow, volume and oxygenation, but cannot directly report neural activity, as it suffers from poor spatiotemporal resolution and specificity compared to the actual neural events. An alternative methodology could be that relying on the responsive, ‘smart’ contrast agents whose relaxivity depends on the concentration of substances directly related to neuronal activity. Ca2+ is an excellent marker closely linked to brain activation and is preferred target for various imaging methods. We report two Gd3+ chelates linked to a modified EGTA moiety that have a relaxivity response to extracellular Ca2+ fluctuations in the brain. The proton relaxivity of both Gd3+ complexes is sensitive to the variation of Ca2+ concentration. They are selective to Ca2+ with respect to the main competitor cation Mg2+. Upon interaction with Ca2+, the complexes exhibit high and reversible relaxivity changes; the relaxivity response of one complex upon addition of Ca2+ exceeds 80. Moreover, the relaxivity changes remain remarkable (>50) even in the medium mimicking the brain extracellular fluid, exhibiting a ~10 relaxivity change in the physiologically relevant Ca2+ concentration range (changes induced during the neural activity). These agents have great potential to be applied as functional MR markers and be used for the visualization of the neural processes. They can substantially increase the specificity and spatial resolution of the MR-detected signals and open new perspectives in fMRI

Применение современных информационных технологий при прогнозировании расхода воздуха для помещений здания

A special attention has been paid lately to creation of the required microclimate in buildings being used for various purposes. In order to create normal air environment in buildings it is necessary to develop forecasting models with the purpose of periodic regulation of air consumption which is supplied to the buildings according to parameters of external climate and character of the work to be carried out in these rooms.The paper considers possibilities to apply modern information technologies for forecasting air consumption. The proposed model allows to create a qualitative air regime in the rooms with due account of power saving.В последнее время уделяется особое внимание созданию требуемого микроклимата в зданиях различного назначения. Для создания нормальной воздушной среды в зданиях необходимо разработать прогнозные модели с целью периодического регулирования расхода воздуха, подаваемого в помещения, в зависимости от параметров наружного климата и характера выполняемой работы в этих помещениях.Рассматриваются возможности применения современных информационных технологий для прогнозирования расхода воздуха. Предложенная методика позволяет создать в помещениях качественный воздушный режим с учетом энергосбережения

WHAT CAN WE EXPECT USING ACE INHIBITOR RAMIPRIL IN PERSONS WITH HIGH CARDIOVASCULAR RISK AND EARLY DISORDERS OF CARBOHYDRATE METABOLISM? LESSONS OF DREAM TRIAL

Primary prevention of diabetes in persons with high cardiovascular risk is an actual problem. Results of DREAM trial are discussed. Influence of ACE inhibitor, ramipril, on risk of diabetes onset in patients with pre-diabetes and low cardiovascular risk is focused. Metabolic effects of other groups of antihypertensive drugs and their ability to prevent diabetes onset are compared. Ramipril three years therapy resulted in normalization in glucose level but did not have effect on frequency of diabetes onset. Change in life-style and regular usage of ACE inhibitor, ramipril, can contribute in normalization of glycemia level in patients with combination of pre-diabetes and arterial hypertension

Guaranteed Solution and its Finding in the Integer Programming Problems

Abstract In the work the definitions of the guaranteed solution and guaranteed suboptimal solution are given for the multiconstraint integer programming problem. A method is developed for finding these solitions. This method is based on the sequental changing of the right hand side of the system of constraints by the dichotomia ous principle

Electrogenic reduction of the primary electron donor P700+ in photosystem I by redox dyes

AbstractThe kinetics of reduction of the photo-oxidized primary electron donor P700+ by redox dyes N,N,N′,N′-tetramethyl-p-phenylendiamine, 2,6-dichlorophenol-indophenol and phenazine methosulfate was studied in proteoliposomes containing Photosystem I complexes from cyanobacteria Synechocystis sp. PCC 6803 using direct electrometrical technique. In the presence of high concentrations of redox dyes, the fast generation of a membrane potential related to electron transfer between P700 and the terminal iron-sulfur clusters FA/FB was followed by a new electrogenic phase in the millisecond time domain, which contributes approximately 20% to the overall photoelectric response. This phase is ascribed to the vectorial transfer of an electron from the redox dye to the protein-embedded chlorophyll of P700+. Since the contribution of this electrogenic phase in the presence of artificial redox dyes is approximately equal to that of the phase observed earlier in the presence of cytochrome c6, it is likely that electrogenic reduction of P700+ in vivo occurs due to vectorial electron transfer within RC molecule rather than within the cytochrome c6-P700 complex