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Prostate cancer is the second most common cancer diagnosed in men worldwide. Measuring the prostate-specific antigen (PSA) is regarded as essential during prostate cancer screening. Early diagnosis of this disease relapse after radical prostatectomy requires extremely sensitive methods. This research presents an approach to development of an ultrasensitive magnetic sandwich immunoassay, which demonstrates the limit of PSA detection in human serum of 19 pg/mL at a dynamic range exceeding 3.5 orders of concentration. Such attractive performance stems, inter alia, from the kinetic analysis of monoclonal antibodies (mAbs) against free PSA to select the mAbs exhibiting best kinetic characteristics and specificity. The analysis is carried out with a label-free multiplex spectral-correlation interferometry compatible with inexpensive single-use glass sensor chips. The high sensitivity of developed PSA immunoassay is due to electronic quantification of magnetic nanolabels functionalized by the selected mAbs and three-dimension porous filters used as an extended solid phase. The assay is promising for PSA monitoring after radical prostatectomy. The proposed versatile approach can be applied for the rational design of highly sensitive tests for detection of other analytes in many fields, including in vitro diagnostics, veterinary, food safety, etc.

Hepatitis B surface antigen (HBsAg) is the most clinically relevant serological marker of hepatitis B virus (HBV) infection. Its detection in blood is extremely important for identification of asymptomatic individuals or chronic HBV carriers, screening blood donors, and early seroconversion. Rapid point-of-care HBsAg tests are predominantly qualitative, and their analytical sensitivity does not meet the requirements of regulatory agencies. We present a highly sensitive lateral flow assay based on superparamagnetic nanoparticles for rapid quantification (within 30 min) of polyvalent HBsAg in serum. The demonstrated limit of detection (LOD) of 80 pg mL-1 in human serum is better than both the FDA recommendations for HBsAg assays (which is 0.5 ng mL-1) and the sensitivity of traditional laboratory-based methods such as enzyme linked immunosorbent assays. Along with the attractive LOD at lower concentrations and the wide linear dynamic range of more than 2.5 orders, the assay features rapidity, user-friendliness, on-site operation and effective performance in the complex biological medium. These are due to the combination of the immunochromatographic approach with a highly sensitive electronic registration of superparamagnetic nanolabels over the entire volume of a 3D test structure by their non-linear magnetization and selection of optimal antibodies by original optical label-free methods. The developed cost-efficient bioanalytical technology can be used in many socially important fields such as out-of-lab screening and diagnosis of HBV infection at a point-of-demand, especially in hard-to-reach or sparsely populated areas, as well as highly endemic regions.

The rapid elimination of systemically administered drug nanocarriers by the mononuclear phagocyte system (MPS) compromises nanomedicine delivery efficacy. To mitigate this problem, an approach to block the MPS has been introduced and implemented by intravenous pre-administering blocker nanoparticles. The required large doses of blocker nanoparticles appeared to burden the MPS, raising toxicity concerns. To alleviate the toxicity issues in MPS blockade, we propose an intrinsically biocompatible blocker, ferrihydrite - a metabolite ubiquitous in a biological organism. Ferrihydrite particles were synthesized to mimic endogenous ferritin-bound iron. Ferrihydrite surface coating with carboxymethyl-dextran was found to improve MPS blockade dramatically with a 9-fold prolongation of magnetic nanoparticle circulation in the bloodstream and a 24-fold increase in the tumor targeted delivery. The administration of high doses of ferrihydrite caused low toxicity with a rapid recovery of toxicological parameters after 3 days. We believe that ferrihydrite particles coated with carboxymethyl-dextran represent superior blocking biomaterial with enviable biocompatibility.

Express and highly sensitive immunoassays for the quantitative registration of cardiac troponin I (cTnI) are in high demand for early point-of-care differential diagnosis of acute myocardial infarction. The selection of antibodies that feature rapid and tight binding with antigens is crucial for immunoassay rate and sensitivity. A method is presented for the selection of the most promising clones for advanced immunoassays via simultaneous characterization of interaction kinetics of different monoclonal antibodies (mAb) using a direct label-free method of multiplex spectral correlation interferometry. mAb-cTnI interactions were real-time registered on an epoxy-modified microarray glass sensor chip that did not require activation. The covalent immobilization of mAb microdots on its surface provided versatility, convenience, and virtually unlimited multiplexing potential. The kinetics of tracer antibody interaction with the “cTnI—capture antibody” complex was characterized. Algorithms are shown for excluding mutual competition of the tracer/capture antibodies and selecting the optimal pairs for different assay formats. Using the selected mAbs, a lateral flow assay was developed for rapid quantitative cTnI determination based on electronic detection of functionalized magnetic nanoparticles applied as labels (detection limit—0.08 ng/mL, dynamic range > 3 orders). The method can be extended to other molecular biomarkers for high-throughput screening of mAbs and rational development of immunoassays.

An ultrasensitive lateral-flow assay is developed for rapid quantitative detection of small molecules on-site. The conceptual novelty, which transfers lateral-flow assays to the category of highly sensitive quantitative systems, is due to employment of a bifunctional ligand combined with volumetric registration of magnetic nanolabels. The ligand provides extremely high affinity for trapping the nanolabels and, simultaneously, efficiently competes with the analyzed molecules for the limited quantity of antigen-binding sites on the nanolabels. The developed assay has been demonstrated as the first express method for measuring in human serum of free thyroxine (fT4). The limit of detection is 20 fМ or 16 fg/ml at the assay time30 min with the dynamic range of 3 orders. Besides, we present the results of first characterization of kinetic parameters of interaction between free thyroxine and monoclonal antibody, as well as of competitive relationship between fT4 and fT4-biotin. The proposed universal platform can be used for ultrasensitive detection of small molecules in human in vitro diagnostics, veterinary, biosafety and counter-terrorism, food quality control, environmental monitoring, etc., as well as for search of new, previously undetectable, diagnostic markers in medicine.

Mycotoxins comprise a frequent type of toxins present in food and feed. The problem of mycotoxin contamination has been recently aggravated due to the increased complexity of the farm-to-fork chains, resulting in negative effects on human and animal health and, consequently, economics. The easy-to-use, on-site, on-demand, and rapid monitoring of mycotoxins in food/feed is highly desired. In this work, we report on an advanced mycotoxin biosensor based on an array of graphene field-effect transistors integrated on a single silicon chip. A specifically designed aptamer against Ochratoxin A (OTA) was used as a recognition element, where it was covalently attached to graphene surface via pyrenebutanoic acid, succinimidyl ester (PBASE) chemistry. Namely, an electric field stimulation was used to promote more efficient {\pi}-{\pi} stacking of PBASE to graphene. The specific G-rich aptamer strand suggest its {\pi}-{\pi} stacking on graphene in free-standing regime and reconfiguration in G-quadruplex during binding an OTA molecule. This realistic behavior of the aptamer is sensitive to the ionic strength of the analyte solution, demonstrating a 10-fold increase in sensitivity at low ionic strengths. The graphene-aptamer sensors reported here demonstrate fast assay with the lowest detection limit of 1.4 pM for OTA within a response time as low as 10 s, which is more than 30 times faster compared to any other reported aptamer-based methods for mycotoxin detection. The sensors hold comparable performance when operated in real-time within a complex matrix of wine without additional time-consuming pre-treatment.

A simple model is designed for an inductive immunosensor in which the magnetic particles are attached to the bioreceptors to form a sandwich on the surface of an inductor. The inductor consists of a coil covered on a silicon oxide wafer. The coil comprises 250 turns of a planar gold wire, which is approximately 200 nm thick and 392 mm long, placed in a circle with a diameter of 2 mm. The model is well characterised by controlling the geometrical and electrical parameters and also the permeability of the magnetic material. To evaluate the feasibility of the model for virus monitoring, a novel inductive immunosensor is designed and for the first time applied for the detection of hepatitis B surface antigen (HBsAg). At first, Fab′ segment of primary anti-HBsAg is immobilised on the coil. Then, the coil is exposed to HBsAg and the complex is introduced to a secondary antibody conjugated with magnetic particles to form an immune-sandwich. Finally, the influence of magnetic particles on the coil inductance is recorded and used as a signal for HBsAg detection. The magnetic inductive immunosensor showed specific responses toward HBsAg with the detection limit of 1 ng mL−1, linear range of 1 to 200 ng mL−1, and a sensitivity of 6 × 10−4 mL ng−1. The experimental results showed a very good agreement with simulation data indicating the compatibility of sensor sensitivity to the expected theoretical values.

The present study investigates the event-related oscillations underlying the motion-onset response (MOR) evoked by sounds moving at different velocities. EEG was recorded for stationary sounds and for three patterns of sound motion produced by changes in interaural time differences. We explored the effect of motion velocity on the MOR potential, and also on the event-related spectral perturbation (ERSP) and inter-trial phase coherence (ITC) calculated from the time-frequency decomposition of EEG signals. The phase coherence of slow oscillations increased with an increase in motion velocity similarly to the magnitude of cN1 and cP2 components of the MOR response. The delta-to-alpha inter-trial spectral power remained at the same level up to, but not including, the highest velocity, suggesting that gradual spatial changes within the sound did not induce non-coherent activity. Conversely, the abrupt sound displacement induced theta-alpha oscillations which had low phase consistency. The findings suggest that the MOR potential could be mainly generated by the phase resetting of slow oscillations, and the degree of phase coherence may be considered as a neurophysiological indicator of sound motion processing.

Thyroid stimulating hormone (TSH) is the first-line marker for initial evaluation of the thyroid gland function. We present a lateral flow immunoassay based on superparamagnetic nanolabels for rapid (25 min) quantitative determination of TSH at a point of care. The demonstrated limit of detection (LOD) of 0.017 μIU/mL in human serum is on the level of third-generation TSH laboratory tests. The wide linear dynamic range of more than 3 orders covers the whole range of clinically relevant TSH concentrations for confident quantitative diagnostics of the gland function from hyper- to hypothyroidism, and different states in-between. The attractive values of LOD and linear dynamic range are due to counting of the superparamagnetic nanolabels over the whole reaction volume by their non-linear magnetization at two frequencies of an alternating magnetic field and detecting the response at combinatorial frequencies. The developed cost-efficient and user-friendly immunoassay can be used for express in vitro diagnostics and long-term quantitative monitoring of thyroid dysfunctions, especially in distant regions, developing countries, and sparsely populated areas.

Active targeting of nanoparticles toward tumors is one of the most rapidly developing topics in nanomedicine. Typically, this strategy involves the addition of cancer-targeting biomolecules to nanoparticles, and studies on this topic have mainly focused on the localization of such formulations in tumors. Here, the analysis of the factors determining efficient nanoparticle targeting and therapy, various parameters such as types of targeting molecules, nanoparticle type, size, zeta potential, dose, and the circulation time are given. In addition, the important aspects such as how active targeting of nanoparticles alters biodistribution and how non-specific organ uptake influences tumor accumulation of the targeted nanoformulations are discussed. The analysis reveals that an increase in tumor accumulation of targeted nanoparticles is accompanied by a decrease in their uptake by the spleen. There is no association between targeting-induced changes of nanoparticle concentrations in tumors and other organs. The correlation between uptake in tumors and depletion in the spleen is significant for mice with intact immune systems in contrast to nude mice. Noticeably, modulation of splenic and tumor accumulation depends on the targeting molecules and nanoparticle type. The median survival increases with the targeting-induced nanoparticle accumulation in tumors; moreover, combinatorial targeting of nanoparticle drugs demonstrates higher treatment efficiencies. Results of the comprehensive analysis show optimal strategies to enhance the efficiency of actively targeted nanoparticle-based medicines.

The current MMN study investigates whether brain lateralization during automatic discrimination of sound stimuli moving at different velocities is consistent with one of the three models of asymmetry: the right-hemispheric dominance model, the contralateral dominance model, or the neglect model. Auditory event-related potentials (ERPs) were recorded for three patterns of sound motion produced by linear or abrupt changes of interaural time differences. The slow motion (450deg/s) was used as standard, and the fast motion (620deg/s) and the abrupt sound shift served as deviants in the oddball blocks. All stimuli had the same onset/offset spatial positions. We compared the effects of the recording side (left, right) and of the direction of sound displacement (ipsi- or contralateral with reference to the side of recording) on the ERPs and mismatch negativity (MMN). Our results indicated different patterns of asymmetry for the ERPs and MMN responses. The ERPs showed a velocity-independent right-hemispheric dominance that emerged at the descending limb of N1 wave (at around 120-160ms) and could be related to overall context of the preattentive spatial perception. The MMNs elicited in the left hemisphere (at around 230-270ms) exhibited a contralateral dominance, whereas the right-hemispheric MMNs were insensitive to the direction of sound displacement. These differences in contralaterality between MMN responses produced by the left and the right hemisphere favour the neglect model of the preattentive motion processing indexed by MMN.

The present study investigates hemispheric asymmetry of the ERPs and low-frequency oscillatory responses evoked in both hemispheres of the brain by the sound stimuli with delayed onset of motion. EEG was recorded for three patterns of sound motion produced by changes in interaural time differences. Event-related spectral perturbation (ERSP) and inter-trial phase coherence (ITC) were computed from the time-frequency decomposition of EEG signals. The participants either read books of their choice (passive listening) or indicated the sound trajectories perceived using a graphic tablet (active listening). Our goal was to find out whether the lateralization of the motion-onset response (MOR) and oscillatory responses to sound motion were more consistent with the right-hemispheric dominance, contralateral or neglect model of interhemispheric asymmetry. Apparent dominance of the right hemisphere was found only in the ERSP responses. Stronger contralaterality of the left hemisphere corresponding to the “neglect model” of asymmetry was shown by the MOR components and by the phase coherence of the delta-alpha oscillations. Velocity and attention did not change consistently the interhemispheric asymmetry of both the MOR and the oscillatory responses. Our findings demonstrate how the lateralization pattern shown by the MOR potential was interrelated with that of the motion-related single-trial measures.

A rapid lateral flow immunoassay is presented that uses carboxyl-modified superparamagnetic nanoparticles as labels that can be quantified by highly sensitive multi-channel electronic readers. The approach is generic in that it is likely to be applicable to numerous small molecules. The method permits both single- and multiplex assays at a point-of-need without sample pretreatment. It is user-friendly and offers attractive characteristics demonstrated here for detection of morphine, fentanyl and methamphetamine in urine. The competitive immunoassay uses commercially available reagents that do not require special permissions. After migration of sample, the lateral flow test strips are subjected to an alternating magnetic field at two frequencies. The response from the nanolabels is readout at a combinatorial frequency from the entire volume of a porous immunochromatographic membrane by the magnetic particle quantification technique. Even trace concentrations can be quantified within ≤20 min with the limits of detection (LOD) of 0.20 ng·mL−1, 0.36 ng·mL−1 and 1.30 ng·mL−1 for morphine, fentanyl and methamphetamine, respectively. The second variant presented here features highly sensitive quantification of haptens (LOD for fentanyl - 0.05 ng·mL−1). This is due to high-affinity trapping of magnetic nanolabels in a universal streptavidin-based test strip, which can be also used for detection of virtually any other small molecule. The third variant is of the multiplexed type and intended for rapid and simultaneous detection of the drugs of abuse in human urine with LODs equal to 0.60 ng·mL−1 and 3.0 ng·mL−1 for morphine and methamphetamine, respectively. In addition to the low LODs, the RSDs did not exceed 7%, 9%, and 11% for methamphetamine, morphine and fentanyl, respectively.

This study investigated the energy-onset and motion-onset responses (N1, P2, cN 1 and cP2 components of the auditory evoked potential) elicited by moving sound stimuli in the passive and active listening conditions. In the passive conditions the subjects were distracted from auditory information; in active conditions they lo- calized the starting and final points of the stimulus trajectory. The sound movement to the left/right from the head midline was produced by linear-changes of the interaural time delay (ITD). The onset of motion was preceded by stationary sound located near the head midline. In the active conditions, the NI component was higher and the P2 component was higher and peaked later as compared to the passive listening. The early and later parts of the motion-onset response (cN 1 and cP2) also were larger in magnitude and peaked later during active listening. Both in active and passive conditions, cNI and cP2 amplitude exhibited increase and latency showed decrease when the stimulus velocity increased. Contralateral asymmetry was found only in the mo- tion-onset responses recorded from the left hemisphere.

A dry-reagent immunomagnetic (DRIM) biosensing platform is developed for rapid high-precision quantitative analyses for in vitro diagnostics. The platform combines the advantages of immunochromatography with highly sensitive quantification of 200-nm magnetic nanoparticles (MP) from the entire volume of lateral flow membranes. The MP are registered by their non-linear magnetization at combinatorial frequencies by a portable reader that offers the detection limit of 60 zeptomoles or 0.4 ng of magnetic nanolabels and extremely wide linear dynamic range of 7 orders. The efficient combination of small MP with large reaction surface of the 3D membranes has permitted the detection in human serum of as low as 25 pg/ml total prostate specific antigen (PSA) during 30-min assay. The featured 3-fold signal increase per every order of concentration within 3.5 orders of magnitude allows precise analysis of antigen concentrations in a wide range. The system also provides the first tool for quantitative MP mapping along the lateral flow strip for easy development and optimization of assays. The DRIM detection can be used for simple, rapid and sensitive quantification of protein biomarkers for in vitro diagnostics both in laboratory and near-patient conditions, for food analysis, environmental monitoring, security, and safety applications.

A multiplex label-free biosensor is developed for diagnostics of autoimmune diseases by highly sensitive measuring in human serum both critical characteristics of autoantibody: concentration and native kinetic parameters that reflect autoantibody aggressiveness to the organism's tissues. The biosensor is based on the spectral-correlation interferometry and image processing of a microarray glass biochip, affordable to be single-used in medical applications. Simultaneous 25-min detection and activity characterization of several autoantibodies in the same serum sample have been demonstrated for anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) as models. The biosensor offers extremely high sensitivity: limits of detection in serum are 1.7 IU/mL and 6 IU/mL for anti-TPO and anti-TG, respectively. The dynamic range covers the whole range of clinically relevant concentrations of the autoantibodies up to 1000 IU/mL. The developed method of characterization of autoantibody activity by recording the kinetics of their binding with free native antigens is based on autoantibody polyvalency. The measurements in clinical serum samples have shown that the native kinetic parameters are independent of concentration. The proposed biosensor and method of native kinetic registration can be used to develop new criteria for comprehensive diagnostics of autoimmune diseases, based not only on traditional measurements of concentration but also on quantitative evaluation of autoantibody aggressiveness. The developed method can be adapted to other label-free sensors such as those based on the surface plasmon resonance, optical waveguides, etc.

A comprehensive study of the interactions between lectins and glycoproteins possessing different glycosylation profiles in the composition of nanoparticles was carried out in order to find specifically interacting protein pairs for the creation of novel classes of multifunctional nanoagets that based on protein-assisted selfassembly. We obtained information about specific interactions of certain lectins with selected glycoproteins as well as about the ability of certain monosaccharides to competitively inhibit binding of glycoproteins with lectins. These protein-mediated interactions may be involved in the formulation of self-assembled nanoparticles for therapy and diagnostics of various diseases.

Human subjects demonstrate a perceptual priority for rising level sounds compared with falling level sounds. The aim of the present study was to investigate whether or not the perceptual preference for rising intensity can be found in the preattentive processing indexed by mismatch negativity (MMN). Reversed oddball stimulation was used to produce MMNs and to test the behavioral discrimination of rising, falling and constant level sounds. Three types of stimuli served as standards or deviants in different blocks: constant level sounds and two kinds of rising/falling sounds with gradual or stepwise change of intensity. The MMN amplitudes were calculated by subtracting ERPs to identical stimuli presented as standard in one block and deviant in another block. Both rising and falling level deviants elicited MMNs which peaked after 250 ms and did not overlap with N1 waves. MMN was elicited by level changes even when the deviants were not discriminated behaviorally. Most importantly, we found dissociation between earlier and later stages of auditory processing: the MMN responses to the level changes were mostly affected by the direction of deviance (increment or decrement) in the sequence, whereas behavioral performance depended on the direction of the level change within the stimuli (rising or falling).

Nanoparticles with biocomputing capabilities could potentially be used to create sophisticated robotic devices with a variety of biomedical applications, including intelligent sensors and theranostic agents. DNA/RNA-based computing techniques have already been developed that can offer a complete set of Boolean logic functions and have been used, for example, to analyse cells and deliver molecular payloads. However, the computing potential of particle-based systems remains relatively unexplored. Here, we show that almost any type of nanoparticle or microparticle can be transformed into autonomous biocomputing structures that are capable of implementing a functionally complete set of Boolean logic gates (YES, NOT, AND and OR) and binding to a target as result of a computation. The logic-gating functionality is incorporated into self-assembled particle/biomolecule interfaces (demonstrated here with proteins) and the logic gating is achieved through input-induced disassembly of the structures. To illustrate the capabilities of the approach, we show that the structures can be used for logic-gated cell targeting and advanced immunoassays.

Precise quantification of interactions between nanoparticles and living cells is among the imperative tasks for research in nanobiotechnology, nanotoxicology and biomedicine. To meet the challenge, a rapid method called MPQ-cytometry is developed, which measures the integral non-linear response produced by magnetically labeled nanoparticles in a cell sample with an original magnetic particle quantification (MPQ) technique. MPQ-cytometry provides a sensitivity limit 0.33 ng of nanoparticles and is devoid of a background signal present in many label-based assays. Each measurement takes only a few seconds, and no complicated sample preparation or data processing is required. The capabilities of the method have been demonstrated by quantification of interactions of iron oxide nanoparticles with eukaryotic cells. The total amount of targeted nanoparticles that specifically recognized the HER2/neu oncomarker on the human cancer cell surface was successfully measured, the specificity of interaction permitting the detection of HER2/neu positive cells in a cell mixture. Moreover, it has been shown that MPQ-cytometry analysis of a HER2/neu-specific iron oxide nanoparticle interaction with six cell lines of different tissue origins quantitatively reflects the HER2/neu status of the cells. High correlation of MPQ-cytometry data with those obtained by three other commonly used in molecular and cell biology methods supports consideration of this method as a prospective alternative for both quantifying cell-bound nanoparticles and estimating the expression level of cell surface antigens. The proposed method does not require expensive sophisticated equipment or highly skilled personnel and it can be easily applied for rapid diagnostics, especially under field conditions.

The spectral dynamics of the EEG rhythmicity during active and passive discrimination of stationary and moving sound stimuli presented according to the oddball paradigm were investigated. Standard stimuli represented stationary midline sounds. Deviant stimuli simulated smooth and stepwise sound source motion (to the left/right from head midline) produced by linear and stepwise changes of interaural time delay. Significant changes of the brain oscillations were found in the frequency range of 3-30 Hz. The dynamics of the moving deviant stimuli (smooth vs. stepwise) had greater impact on theta-rhythm power in active listening conditions: a stronger theta-power increase was evoked by the stepwise sound motion as compared to smooth motion. Significant increase in theta-power was also observed with rightward sound displacement as compared to leftward displacements. Active deviant discrimination reduced alpha-power (8-11 Hz) mostly during smooth deviant motion. The power increase of lower alpha-oscillations (12-15 Hz) was stronger with step- wise motion than with smooth motion of deviants. The interhemispheric asymmetry of beta-power decrease in active conditions (as compared to passive) was found in the whole beta-range. The sup- pression of beta-power was stronger at the right hemisphere than at the midline or left hemisphere and showed no dependence on spatial properties of the deviant stimuli. This asymmetry may be related to selective attention to task-relevant sounds and with preparation to motor response. Generally, active auditory discrimination resulted in stronger deviant-related changes of the wide-ranged EEG spectral power than passive discrimination with attentional tuning to task-irrelevant stimuli.

The present study investigates the hemispheric asymmetry of auditory event-related potentials (ERPs) and mismatch negativity (MMN) during passive discrimination of the moving sound stimuli presented according to the oddball paradigm. The sound movement to the left/right from the head midline was produced by linear changes of the interaural time delay (ITD). It was found that the right-hemispheric N1 and P2 responses were more prominent than the left-hemispheric ones, especially in the fronto-lateral region. On the contrary, N250 and MMN responses demonstrated contralateral dominance in the fronto-lateral and fronto-medial regions. Direction of sound motion had no significant effect on the ERP or MMN topography. The right-hemispheric asymmetry of N1 increased with sound velocity. Maximal asymmetry of P2 was obtained with short stimulus trajectories. The contralateral bias of N250 and MMN increased with the spatial difference between standard and deviant stimuli. The results showed different type of hemispheric asymmetry for the early and late ERP components which could reflect the activity of distinct neural populations involved in the sensory and cognitive processing of the auditory input.

The current study investigates auditory event-related potentials (ERPs) and mismatch negativity (MMN) during active and passive discrimination of stationary and moving sound stimuli presented according to the oddball paradigm. Standard stimuli represented stationary midline sounds. Deviant stimuli simulated sound source location shifts (to the left/right from head midline) produced by linear or stepwise changes of interaural time delay (ITD). The event-related responses were evaluated by peak amplitudes of N1 waves and mean amplitudes of MMN, P3a, P3b and reorienting negativity (RON) components. The N1 amplitude was larger in active than in passive conditions, and was unaffected by spatial dynamic changes of the deviant stimuli. The deviant motion pattern (smooth or stepwise) affected only MMN and RON obtained in passive listening conditions. Abrupt deviant displacement elicited larger MMN and RON components than smooth motion. Drawing listeners' attention to the deviant stimuli resulted in suppression of MMN/RON sensitivity to auditory motion pattern.

The parallel psychophysical and MMN study focused at the sensitivity of human hearing system to variations in velocity of sound image movement. The motion of sound stimuli with various velocities in the 450 deg/s to 732 deg/s range in increments of 6 deg/s to the left or to the right from the head midline was simulated by introducing linear changes of interaural delay into dichotic stimuli. The psychophysical experiments were designed according to the 2-alternative forced choice paradigm. The subjects were presented by pairs of moving stimuli and were asked to decide which moved faster. The stimuli created for the present study ensured that the subjects performed the discrimination task without relying on associated cues of sound displacement or duration. The psychophysical measures were compared with electrophysiological indexes of sound processing (auditory evoked responses (ERPs) and mismatch negativity (MMN)). Significant MMN was elicited by the difference of 170 deg/s between the reference and test velocity, which corresponded to the relative velocity increase of 38%. At the same time, the difference thresholds for velocity were much higher and exceeded 50%. The results suggest that MMN magnitude depended on the velocity difference between standard and deviant stimuli and was more sensitive to velocity difference than psychophysical measure.

A 3-channel biosensor based on spectral correlation interferometry (SCI) has been adapted for direct optical detection of antigens by measuring changes in thickness of a biolayer on functionalized glass slips employed as affordable single-use sensor chips. The instrument is insensitive to the bulk refractive index of a solution under test and provides signals in metrological units (pm or nm). Using real-time monitoring with the SCI, protocols for fabrication of sensor chips with different functional (epoxylated, carboxylated, and biotinylated) surfaces for antibody immobilization have been developed and optimized to minimize chip-to-chip variations and achieve better limit of detection (LOD), shorter assay time, and longer shelf life. The optimized coupling surfaces have been compared for detection of human serum albumin (HSA) used as a model agent of medical significance. The dynamic ranges for measuring the HSA concentration were 0.07-20, 0.12-30, and 0.25-10 μg/ml, and the assay durations were less than 20, 15, and 30 min for the epoxylated, carboxylated, and biotinylated chips, respectively. The advantages of each type of sensor chip have been shown, namely, the carboxylated chips feature the shortest assay time, the epoxylated ones demonstrate the best LOD, and the biotinylated chips exhibit the longest shelf life in an unprotected environment. The developed protocols of antibody immobilization can be used in different biosensors and assay techniques including those based on fluorescent, magnetic or plasmonic labels, etc. The SCI is well compatible with various partially transparent layers used in biosensing and with microarrays for multi-analyte detection.

The magnitude of spatial distance between sound stimuli is critically important for their preattentive discrimination, yet the effect of stimulus context on auditory motion processing is not clear. This study investigated the effects of acoustical change and stimulus context on preattentive spatial change detection. Auditory event-related potentials (ERPs) were recorded for stationary midline noises and two patterns of sound motion produced by linear or abrupt changes of interaural time differences. Each of the three types of stimuli was used as standard or deviant in different blocks. Context effects on mismatch negativity (MMN) elicited by stationary and moving sound stimuli were investigated by reversing the role of standard and deviant stimuli, while the acoustical stimulus parameters were kept the same. That is, MMN amplitudes were calculated by subtracting ERPs to identical stimuli presented as standard in one block and deviant in another block. In contrast, effects of acoustical change on MMN amplitudes were calculated by subtracting ERPs of standards and deviants presented within the same block. Preattentive discrimination of moving and stationary sounds indexed by MMN was strongly dependent on the stimulus context. Higher MMNs were produced in oddball configurations where deviance represented increments of the sound velocity, as compared to configurations with velocity decrements. The effect of standard-deviant reversal was more pronounced with the abrupt sound displacement than with gradual sound motion.

In patients with epileptic lesions in the hippocampus as well as in the temporal lobe and hippocampus simultaneously, studies were made on the perception of sound signals imitating sound source movement. It was established that hippocampal lesion results in disturbance of estimation of sound spatial characteristics which manifests in a change accuracy of localization and shortening of subjective sound image movement trajectory. Maximum disturbances of localization function are observed during lesions of hippocampus and temporal lobe. Possible neurophysiological mechanism underling observed disturbances are considered.

Auditory evoked response and mismatch negativity potential have been studied using the reversed odd-ball paradigm of standard and deviant stimulus presentation. In the experiments, three types of spatial sound stimuli (stationary and moving either gradually or abruptly from the head midline) were presented in three configurations. Each configuration employed one stimulus type as standard and the other two types as deviants. It was demonstrated that the configuration reversals influenced significantly the evoked response and mismatch negativity. The results obtained are discussed as the possible evidence of the categorical perception of auditory motion revealed at the earlier stages of sound processing in the hearing system.

The review presents the data concerning auditory event-related potentials and their "mismatch negativity" component under conditions of stationary and moving sound source localization. Both free-field and dichotic experimental conditions are considered. The interhemispheric asymmetry of the brain responses elicited by the sound sources of various spatial properties is also discussed.

The peptide from C-terminal domain of MCP-1 (Ingramon) has been shown to inhibit monocyte migration and possess anti-inflammatory activity in animal models of inflammation and post-angioplasty restenosis. Here, we investigate the effect of Ingramon treatment on blood levels of acute-phase reactants and chemokines in patients after coronary stenting and the mechanisms of Ingramon anti-inflammatory activity. Eighty-seven patients with ischemic heart disease (IHD) who faced the necessity of coronary angiography (CA) were enrolled. In 67 patients, one-stage coronary stenting was performed; 33 of them were treated with Ingramon in addition to standard therapy. Twenty patients underwent CA only. High-sensitivity C-reactive protein (hsCRP) and fibrinogen blood levels were detected routinely. The chemokine concentration in plasma was measured by enzyme-linked immunosorbent assay (ELISA) or cytometric bead array-based immunoassay. Intracellular Ca2+ levels and cell surface integrin exposure were assayed by flow cytometry. MCP-1 dimerization was studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). MCP-1–heparin binding was assessed with a biosensor and ELISA. Ingramon treatment was accompanied by less pronounced elevation of hsCRP and fibrinogen levels and decreased MCP-1 concentration in plasma in patients after coronary stenting. Ingramon had no effect on MCP-1 interaction with cell receptors or MCP-1 dimerization, but inhibited MCP-1 binding to heparin. The anti-inflammatory activity of the peptide may be mediated by an impaired chemokine interaction with glycosaminoglycans.

Results of endovascular treatment of cerebral aneurysms in acute period of hemorrhage complicated by the development of vasospasm in 80 patients were analyzed. The results of treatment of patients with vasospasm were worse. The appearance of vasospasm did not depend of the severity of the patient's state, so all the patients independent on their state need prophylactic measures against this complication. Based on the analysis a strategy of embolization of aneurysms in acute period of hemorrhage complicated by the development of vasospasm was worked out.

Analysis of experimental data about the quantitative and qualitative chemical make-up of air in the orbital station Mir and International space station (ISS) showed a permanent presence of silicon. The main source of silicon contaminants seems to be a variety of polymethyl siloxane liquids and siloxane coating of electronics. The article describes the volatile silicon contaminants detected in space stations air. To control concentrations of silicon, the existing air purification system needs to be augmented with carbons having the micropore entrance larger than diameters of silicon-containing molecules. It is also important to elaborate the technology of polymethyl siloxane liquids synthesis so as to reduce the amount of volatile admixtures emission and to observe rigorously the pre-flight off-gassing requirements with special concern about silicon coatings.

An analysis of results of surgical treatment of 79 patients aged from 41 to 72 years with hypertensive intracerebral hematomas of supratentorial localization has shown that results of surgical treatment depended on the severity of the patients' state, the degree of impairment of consciousness, volume and localization of hematoma, ventricular hemorrhage and in less degree on the terms of operation and the degree of displacement of the median structures of the brain. The endoscopic techniques proved to be preferential in hematomas of the lateral and mixed localizations with the volume not more than 60 cm3. The developed method using a cannula allowed abandon open operations in most patients with the lateral and mixed hematomas. The postoperative lethality became less by 9.9%.

The paper deals with the ability of human olfaction to identify odours associated with thermal destruction of polymers. The investigations confirmed the ability of early detection of equipment overheating and subjective odour evaluation using the 5-point intensity scale and calculating the relation of odour intensity to the maximum admissible concentration of volatile chemical contaminants aboard piloted space vehicles. Emission of gases by polymers in electrical equipment starts with heating temperature rise to 100 degrees C. A new odour smelled by only some of humans due to individual perception signifies typically that emitted gases are below MAC for space vehicle. Odour sensed by everyone though not irritating signifies, as a rule, of chemical contamination above MAC but not contingency. Symptoms of irritation by products of thermal destruction of polymers signify contingency and require the use of personal protection equipment.

The purpose of this study was to evaluate dynamics of B-waves' amplitudes (BWA) of blood flow velocity (BFV) in patients with cerebrovascular diseases during endovascular operations. We examined 12 patients with neurovascular pathology during neuroendovascular interventions. Patients were divided into two groups: 1st group (6 cases)--without intraoperative neurological complications, 2nd group (6 cases)--with complications. Bilateral monitoring of BFV in middle cerebral arteries was carried out applying Multi Dop X. To estimate BWA Fourier analysis was used. In the 1st group preoperative BWA on the affected side was 3.9 +/- 0.6 cm/s. Intraoperative (during an access to pathologic formation and its embolisation) BWA increased up to 7.7 +/- 1.1 cm/s (p0.05). Postoperative BWA decreased to 4.2 +/- 0.8 cm/s. In the 2nd group the preoperative BWA on the affected side was 9.6 +/- 1.1 cm/s (p0.05), thus higher than in the 1st group. Intraoperatively we observed further increase of BWA up to 12.1 +/- 2.6 cm/s, accompanied by occurrence or increase of neurological symptoms. Postoperative BWA decreased to 10.4 +/- 2.9 cm/s, whereas we didn't observe regression of neurological symptoms.

The literature data indicating a significant impairment of the basic parameters of male reproductive function in the last decades are analyzed and summarized. This impairment is expressed in the reduction of spermatogenic activity, increased incidence of genital malformations and testicular tumors. The listed changes are reviewed in comparative aspect and include examples of some species of wild animals. The data on the factors responsible for occurrence of pathological changes in male reproductive system are analyzed.

The work presents experimental data on certain changes in electrical responses of the auditory system's midbrain centre in a contraphasic binaural presentation of sound impulse series. Neuronal cortical activity is selective in respect to dynamic interaural changes of signals' phasic spectre which may serve as a basis for the mechanisms of localising a moving source of sound. Human auditory evoked potentials reveal a manifestation of memorizing the auditory image movement direction as shown by appearance of stimuli deviant from standard mismatch negativity.

Based on the multiyear experience of hygienic control of the orbital stations, there are three causes of contingent air pollution: leakage of service system pipeline with chemical working bodies, spills of reagents used in biochemical and technological experiments, and air pollution by products of thermal oxidative degradation of nonmetallic materials. The authors describe their experience in successful elimination and prevention of hazardous consequences of fire aboard the space stations. Analysis of air pollution dynamics after actual fire events in the space station modules showed that it approximates a two-chamber air flow model with two phases of pollutant equilibration: first a rapid fall of concentration in the module on fire till air in the modules gets completely mixed, and then slow elimination of harmful pollutant from air. Identified were markers,--propylene and methylmetacrilate,--reacting to first signs of fire. Carbonic acid nitriles were recognized as toxic products of destruction. The positive effect of intermodular ventilation on dilution of toxic products of thermal oxidative destruction of materials was demonstrated. Satisfactory agreement of calculated and factual pollutant concentrations on board Mir permitted conclusion on applicability of the theoretical model to prediction of levels of air pollution due to contingency.

The EPs of the inferior colliculus and auditory cortex in anaesthetized guinea pigs and the long latency auditory EPs in alert humans were studied. The stimuli consisted of binaurally presented pairs of clicks used as a masker, and the probe, with a variable time delay between them. The greatest relative differences between out-of-phase and in-phase probe responses were observed at the beginning of the recovery course. They averaged as 1.6, 1.5 and 1.4 for the responses of the inferior colliculus, auditory cortex and long latency potentials, resp., at the stimuli intensities of 50-65 dB SPL, and then decreased to zero during the time course of the probe response recovery. Correlation of this parameter with the stimulus intensity was positive.

Problems concerning regularities and mechanisms of the environmental factor influence on human reproductive system are discussed. It is indicated that the response of reproductive system to external challenges is based on the evolutionary formed links between the structures responsible for reproductive organ function (epiphysis, hypothalamus, pituitary), the nature of environmental factors and the regularities of their changes depending on the season and geographical location. Damaging external challenges caused by biosphere pollution by waste products of human economic activity and extreme ecological conditions are realized both by direct influence on target tissues (ionizing radiation) and indirectly through neuroendocrine mechanisms regulating reproductive organs function. Factors and regularities of the development of diseases and pathological conditions of human reproductive system, caused by external challenge including the injurious industrial factor influence were analyzed.

The subject of inquiry was perception of moving sound along the vertical at various angular velocities. The sound was switched around by 13 sequential dynamics installed on a 180 degrees arc. Threshold values for discriminating angular velocities at 150, 167, 188, 214, 250, 300, 375, and 500 degrees/s were measured with the minimal borderlines method. Six test-subjects with normal hearing participated in the experiment. Acceleration of sound movement in the range from 167 up to 500 degrees/s leads to essentially linear increases in absolute threshold values and monotonous increases in relative threshold values.

242 cases of brain arterio-venous malformations (AVM) are analysed clinically and anatomically. Their pathology, histological, ultrastructural and immunohistochemical characteristics, therapeutic pathomorphosis are described. The concept is suggested according to which AVM is a collective term including true developmental defects, dysembryogenetic tumors and outcomes of various pathologic processes (trauma, brain circulation and compensatory-adaptive disturbances, etc.). The necessity of therapeutic methods corrections in agreement with the disease pathogenesis is outlined.

Lateralization of moving fused auditory images (FAIs) was studied under dichotic stimulation, with FAI movement from the right and left ears to midline. The movement was produced by the gradual change of interaural time delay (from +/- 630 to 0 microseconds) in a binaurally presented click train in which a constant interaural intensity difference (IID) between +/- 13 dB was also imposed. The task of the subjects was to show with her/his finger the point on the head surface where the FAI trajectory's ending or starting points were perceived. With IID change within +/- 13 dB, the FAI movement trajectory shifted toward the ear receiving the more intense stimulus. The length of the movement trajectory shortened with IID increase. Functions relating the value of perceived lateral position (Y) of the movement trajectory's ending and starting points to IID value (X) were nearly linear: Y = AX + B. These functions differed in their characteristics whether the movement was to the right versus to the left of midline. They also differed from analogous functions for stationary FAI. At IID = 0 the FAI movement trajectory's endpoint was shifted from midline in the direction of movement. Equivalence ratio for IID and ITD were estimated to be 51 and 29 microseconds/dB respectively for the trajectory's starting and ending points. The IID factor could be several times as effective in moving FAI lateralization as the ITD factor.

The paper analyzes the outcomes of surgical treatment made in 431 patients in 1971-1994. Multimodality treatment for this abnormality was used, which reduced postoperative mortality.