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Fitting range of the BAHA Cordelle.

The performance of the most powerful Bone-Anchored Hearing Aid (BAHA) currently available, the BAHA Cordelle, was evaluated in 25 patients with severe to profound mixed hearing loss. Patients showed bone conduction thresholds at 500, 1000 and 2000 Hz, ranged between 30 and 70 dB HL, and an additional air-bone gap of about at least 30 dB. With the BAHA Cordelle, free-field thresholds improve relative to bone-conduction thresholds with 1.5, 5.0, 17.8, and 4.3 dB at 500, 1000, 2000, and 4000 Hz, respectively, with substantial inter-individual variability. The differences in unaided air conduction thresholds and aided free-field thresholds amount to 45.3, 45.8, 47.5, and 43.5 dB at 500, 1000, 2000, and 4000 Hz, respectively. Speech perception, measured both with monosyllables of the consonant-vowel-consonant type and with bisyllables, showed highly similar results. The fitting range of a (linear) hearing aid is determined by its gain characteristics. Requiring aided speech reception thresholds at or better than 65 dB SPL results in an upper limit of the fitting range of the BAHA Cordelle for bone-conduction thresholds of 51, 56, 67, and 58 dB HL at 500, 1000, 2000, and 4000 Hz, respectively. The dynamic range provided by the BAHA Cordelle was estimated from loudness growth functions at 500, 1500, and 3000 Hz employing 7-point categorical scaling. On average, aided loudness growth functions exhibit normal slopes but they level off at input levels of about 80, 70, 65 dB SPL for 500, 1500, and 3000 Hz stimuli, respectively. Measurements with a skull simulator demonstrated that the levelling-off reflects saturation of the output of the Cordelle. The relatively low saturation levels of the device suggest that increasing maximum output levels may be a worthwhile consideration for candidates with more profound sensorineural loss.

Acoustic Stimulation↗

Forward-viewing CMUT arrays for medical imaging.

This paper reports the design and testing of forward-viewing annular arrays fabricated using capacitive micromachined ultrasonic transducer (CMUT) technology. Recent research studies have shown that CMUTs have broad frequency bandwidth and high-transduction efficiency. One- and two-dimensional CMUT arrays of various sizes already have been fabricated, and their viability for medical imaging applications has been demonstrated. We fabricated 64-element, forward-viewing annular arrays using the standard CMUT fabrication process and carried out experiments to measure the operating frequency, bandwidth, and transmit/receive efficiency of the array elements. The annular array elements, designed for imaging applications in the 20 MHz range, had a resonance frequency of 13.5 MHz in air. The immersion pulse-echo data collected from a plane reflector showed that the devices operate in the 5-26 MHz range with a fractional bandwidth of 135%. The output pressure at the surface of the transducer was measured to be 24 kPa/V. These values translate into a dynamic range of 131.5 dB for 1-V excitation in 1-Hz bandwidth with a commercial low noise receiving circuitry. The designed, forward-viewing annular CMUT array is suitable for mounting on the front surface of a cylindrical catheter probe and can provide Doppler information for measurement of blood flow and guiding information for navigation through blood vessels in intravascular ultrasound imaging.

Electric Capacitance↗

Physiology of the aged Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli.

1. Presbycusis, age-related hearing loss, is an ever increasing problem in our aging society. It involves changes in both the peripheral and central portions of the auditory system. The inferior colliculus (IC) has been shown to display age-related changes including decreased gamma-aminobutryic acid (GABA) levels, decreased glutamate decarboxylase levels, and decreased binding by GABAB receptors, as well as rearrangement of axon terminals in aging Fischer 344 (F344) rats. Age-related physiological changes have also been noted in the ICs of C57 and CBA mice. 2. Given the age-related alterations in the inhibitory neurotransmitter system, we hypothesized that aged F344 rats would show alterations in the physiological response properties of their IC neurons due to an imbalance in the relative levels of inhibition and excitation affecting the neuronal firing. 3. In vivo extracellular single-unit recordings were made from 297 IC neurons in ketamine/xylazine-anesthetized aged (24 mo) F344 rats. Locations of recorded units were determined from the electrode track marks and horseradish peroxidase marks. Results were compared with those obtained from young adult (3 mo) animals. 4. Average threshold increased from 25.4 dB SPL in young rats to 56.1 dB SPL in aged rats. 5. Although there was a reduction in the percentage of units recorded at either extreme of the frequency range in aged animals, the characteristic frequency (CF) range and mean did not differ between the two groups. 6. For the IC as a whole, no differences were noted in spontaneous activity, first spike latency, dynamic range, percentage of units with nonmonotonic contralateral CF tone rate/intensity functions (RIFs), or percentage of units sensitive to change in CF tone presentation rate. 7. In aged rats, a higher percentage of units was poorly responsive to auditory stimulation. 8. In the aged rat, there was a 12% reduction in the maximum discharge rate, a 12% increase in the percentage of units classified as onset in their temporal response pattern, and an 18% increase in the breadth of the isointensity functions at 30 dB above threshold. 9. Age-related changes in the central nucleus of the IC (CIC) frequently differed from those observed in the external cortex of the IC (ECIC). The percentage of units classified as having nonmonotonic contralateral tone RIFs decreased with age in the CIC but increased with age in the ECIC, and the percentage of units classified as onset in their temporal response pattern increased with age in the CIC but did not change with age in the ECIC. 10. The results of this study support the hypothesis that there is an age-related shift to higher intensities in the working range of most CIC units along with a small, selective deficit in inhibitory processing. When considered in conjunction with the mouse aging studies conducted by other researchers and with the results of a similar study of single units in the visual system (lateral geniculate nucleus) of young and aged rhesus monkeys, these results suggest that compensatory mechanisms are highly active in sensory systems as animals age. Despite deficits that lead to reduced input to the IC and neurochemical changes affecting neurotransmitter levels, IC neurons in aged rats are able to respond to most simple auditory stimuli in a fashion quite similar to that observed in young rats.

Age Factors↗

Automated platelet counts: accuracy, precision, and range.

The automation of platelet counting is essential in laboratories performing a large number of procedures with high precision. Maintaining this precision and establishing accuracy require an understanding of the special problems of counting platelets, including: (1) the large dynamic range of the measurement, (2) the variable size and aggregability of platelets, and (3) the specific requirements of a quality-control method. In evaluating these problems, we designed experiments that measured the linearity and precision of two types of platelet counters, light scattering and electronic aperture impedance, and that evaluated the suitability of commercially available reference materials. The results show that the instrumentation is excellent and the reference materials are good; such that, given a well-planned quality-control method as presented here, the automated platelet count gives a rapid result with precision and accuracy.

Calibration↗

DNA digest analysis with capillary electrophoresis.

DNA digest analysis with polymer-filled capillaries in capillary electrophoresis is described. The samples analyzed consisted of commercially available standards including a 100 base pair ladder with repeating units up to 2000 base pairs. Three DNA digests covered the most common small fragment ranges: up to 600 base pairs, up to 1500 base pairs and from 100 to 2500 base pairs. All samples were separated by traditional slab gel electrophoresis at various agarose concentrations and by automated capillary electrophoresis. The capillary electrophoretic separations were achieved with noncross-linked polyacrylamide from 6% monomer solutions. The acrylamide was polymerized inside the capillary, which was coated with a methacryloxysilane to insure binding of the polyacrylamide to the capillary wall. With 6% columns, excellent separations were observed up to 600 base pairs with base line resolution for fragments differing in less than 10 base pairs. Resolution power for fragments between 600 and 2200 decreased to about 300 base pairs. Compared to slab gels, capillary electrophoresis achieved better resolution in the low fragment range, whereas with the reported column composition, slab gels were superior above 600 base pairs. Fast access to the analysis of a specific sample, automation, and a larger dynamic range for sample load are further benefits of a DNA digest analysis by capillary electrophoresis.

Autoanalysis↗

Response of the charophyte Nitellopsis obtusa to heavy metals at the cellular, cell membrane, and enzyme levels.

The responses of the freshwater macroalga Nitellopsis obtusa to heavy metal (HM) salts of Hg, Cd, Co, Cu, Cr, and Ni were assessed at different levels: whole-cell mortality (96-h LC(50)), in vivo cell membrane (45-min depolarization of resting potential, EC(50)), and enzyme in plasma membrane preparations (K+, Mg2+-specific H+-ATPase inhibition, IC(50)). To measure ATPase activity, a novel procedure for isolation of plasma membrane-enriched vesicles from charophyte cells was developed. The short-term ATPase inhibition assay (IC(50) from 6.0 x 10(-7) to 4.6 x 10(-4) M) was slightly more sensitive than the cell mortality test (LC(50) from 1.1 x 10(-6) to 2.6 x 10(-3) M), and the electrophysiological test with the end point of 45-min depolarization of resting potential was characterized by less sensitivity for HMs (EC(50) from 1.1 x 10(-4) to 2.2 x 10(-2) M). The variability of IC(50) values assessed for HMs in the ATPase assays was close to that of LC(50) values in the mortality tests (CVs from 33.5 to 83.5 and from 12.4% to 57.7%, respectively), whereas the EC(50) values in the electrophysiological tests were characterized by CVs generally below 30%. All three end points identified two separate HM groups according to their toxicity to N. obtusa: Co, Ni, and Cr comprised a group of less toxic metals, whereas Hg, Cu, and Cd comprised a group of more toxic metals. However, the adverse effects within each group were discriminated differently. For example, the maximum difference between the highest and lowest LC(50) for the group of less toxic metals in the long-term mortality test was approximately 60% of the response range, whereas the corresponding difference in IC(50) values in the ATPase assay was 30%. In contrast, the LC(50) values of the more toxic metals occupied only 10% of the response range, whereas the IC(50) values were spread over 70%. Further investigation should be done of the underlying mechanism or mechanisms responsible for the observed differences in the dynamic range of a particular end point of the groups of toxicants of varying strength.

Cell Membrane↗

A refractive tilting-plate technique for measurement of dynamic contact angles.

The contact angle is a critical parameter in liquid interface dynamics ranging from liquid spreading on a solid surface on earth to liquid motion in partially filled containers in space. A refractive tilting-plate technique employing a scanning laser beam is developed to conduct an experimental study of a moving contact line, with the intention of making accurate measurements of the contact angle. The technique shows promise as an accurate and potentially fully automated means to determine the velocity dependence of the contact angle at the intersection of the interface between two transparent fluids with a transparent solid surface. Ray tracing calculations are included to reinforce the measurement concept. The principal experiments were conducted at speeds ranging from 0.05 to 1.00 mm/s, both advancing and receding, using an immiscible liquid pair (nonane/formamide) in contact with glass. The contact angle was found to depend for practical purposes only on the sign of the velocity and not on its magnitude for the range of velocities studied. Other observations revealed a bimodal behavior of the contact line that depends on which liquid first contacts the glass, with resulting drift in the dynamic contact angle with time.

Journal Article↗

Optimization of post-column chemiluminescent detection for low-molecular-mass conjugates of acridinium esters.

In this study, various factors are examined that affect the post-column chemiluminescence detection of low-molecular-mass compounds labelled with acridinium esters, using 9-phenyl acridinium ester (PAE) as the initial model. Reaction conditions examined included the effect of hydroxide or hydrogen peroxide concentration, ionic strength and surfactant content on the degree and length of light production by the acridinium ester label. Based on these results, a system was developed for the post-column detection of acridinium ester conjugates in HPLC. The final post-column reactor had optimum conditions similar to those for a benchtop luminometer but gave light production over slightly longer periods of time and had a broader range of reagent concentrations that gave a maximum response. The detection limit of this system for PAE was 7 x 10(-19) mol per injection, with linear and dynamic ranges that extended up to 3 x 10(-15) and 3 x 10(-13) mol, respectively. Some preliminary work was conducted examining the use of this system in chromatography-based competitive binding immunoassays with a thyroxine-acridinium ester conjugate being used as the label. The estimated limit of detection was 2.5 x 10(-17) mol (or roughly 10(-12) M for a 25 microliters sample) based on the retained fraction of the conjugate.

Acridines↗

Electrophysiological study of spinothalamic inputs to ventrolateral and adjacent thalamic nuclei of the cat.

1. Extracellular and intracellular methods were used to record from fibers and neurons in the ventral lateral (VL) and adjacent nuclei of the cat thalamus. The receptive fields of the recorded units were analyzed and the units tested for inputs from the medial lemniscus (ML) and spinothalamic tract (STT) by electrical stimulation of the dorsal columns (DC) and ventrolateral funiculus (VLF) at the C2-3 spinal level. 2. Thirty-eight STT fibers were isolated in the thalamus. Their conduction velocities ranged from 15 to 75 m/s (mode 36 m/s). Adequate stimuli were found for 23 of these fibers. Seventeen were low-threshold (LT), 3 were wide-dynamic-range (WDR), and 3 were high-threshold (HT) units. 3. Five STT fibers were intra-axonally injected. Three were sufficiently well filled for analysis of their terminal fields. An intermediate-velocity STT fiber (conduction velocity 38 m/s) had a 4.3-microns axon and a single large terminal field in the central lateral nucleus (CL). The other two STT fibers were smaller, with diameters of 2.5 and 2.3 microns, conduction velocities of 15 and 19 m/s, and terminal fields made up of a few small boutons at the borders of the ventral posterior lateral nucleus (VPL). 4. Of 319 neurons isolated, 14 out of 129 (10.8%) in VL, 14 out of 76 (18.4%) in the VPL or ventral posterior medial (VPM) nucleus, 27 out of 64 (42.2%) in the CL nucleus, and 5 out of 50 (10%) in the reticular nucleus (R) responded at latencies less than 50 ms to VLF stimuli. A train of three pulses was more effective in driving VLF-responding neurons in all these nuclei than a single pulse. VLF-responding cells were widely dispersed in VL, concentrated in a focus in CL, and distributed around the borders of VPL. Most of those in VL and a small number in CL could be antidromically activated by stimulation of motor cortex. 5. Latencies of presynaptic responses (STT fibers) to VLF stimulation were short and varied from 0.8 to 3.9 ms (mode 1.6 ms). Despite this, very few fast-responding neurons were found. These were six VPL neurons (2.5 to 4 ms), one VL neuron (3 ms), and four CL neurons (3-4 ms). The initial spike latencies of the majority of thalamic neurons responding to VLF stimulation appeared in two peaks, one between 6 and 8 ms and the other at 10-15 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Development and evaluation of a time-resolved immunofluorimetric assay for thyrotropin.

The assay described in this article is based on microtitre plate technology; it employs an europium label. The streptavidin-biotin system has been used and all components are commercially available. The lower detection limit of the assay is below 0.003 mU/l; the standards are made up in newborn calf serum. Correlation with a commercially available immunoluminometric assay (Berilux--Behringwerke) was excellent (r = 0.92, n = 201 data pairs, range covered 0-10 mU/l). The regression line using a double logarithmic transformation was: (log y) = 0.91 (log x)-0.08. The assay precision at the clinical limits of decision--i.e. between hyper- and euthyroidism (0.2 mU/l) and eu- and hypothyroidism (4 mU/l)--was acceptable. The median coefficient of variation was 1.93% in the range 0.02-1 mU/l and 2.11% in the range 1.0-3.5 mU/l, with both values being determined from precision profiles using 214 and 188 data pairs respectively. Inter-assay coefficients of variation determined in over 30 consecutive assays were under 6% in the range 1.3-20 mU/l. From 201 sera measured in both assays, 194 sera gave clinically identical values; 8 sera gave clinically discrepant values. The assay has a large dynamic range covering a concentration range of above 5 decades, with the count ratio between the 100 mU/l standard and the zero standard being in excess of 4150:1. A high dose hook effect was first seen in excess of 500 mU/l. The maximum signal was achieved around 150 mU/l, which registered around 8 x 10(6) counts per second, a figure more than 8000 times higher than that in the zero standard.

Antibodies, Monoclonal↗

A technique to evaluate the performance of computerized ECG analysis systems.

No objective method to test computerized ECG systems has been available. Until now, tests have been conducted separately for instrumentation and algorithms. Hence, to facilitate objective verification and testing of modern computerized ECG equipment, a dedicated high resolution, low noise instrument (an "electronic test patient") has been developed. The purpose of this communication is to describe this new instrument and its electrocardiographic database. The instrument is designed not to cause any disturbances to the original ECG signals in the frequency range from 0 to 1 kHz. The input channels accommodating standard 12-lead and 3-lead Frank systems are sampled simultaneously at 10 kHz each with 90 dB dynamic range. The overall RMS noise figure of the instrument is 1 microV. The integral part of the instrument is a high resolution, high bandwidth minidatabase consisting of selected A-type and B-type verified electrocardiograms such as infarctions, ventricular hypertrophies, atrial fibrillations, etc. The minidatabase was collected with the aid of a computerized ECG system, which has a program for searching for specific electrocardiographic diagnosis. Each database record consists of simultaneous electrocardiographic signals of all standard leads and Frank leads, and a validated diagnostic report. A system under test is typically connected via its patient cable to the analog output of the instrument. The testing is performed with reference to the validated ECG from the database. In that way, our minidatabase is compatible with any electrocardiographic system. The only similar database assembled for testing purposes is that of the CSE group.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Systems↗

Determination of the immunomodulator laquinimod in human plasma by liquid chromatography/tandem mass spectrometry; development, validation and application of two methods in clinical pharmacokinetic profiling.

Laquinimod (ABR-215062) is a synthetic compound currently undergoing clinical development for oral treatment of multiple sclerosis. The present paper describes the development, validation and clinical application of two rapid and sensitive methods for the determination of ABR-215062 in human plasma. Both methods use liquid chromatography/tandem mass spectrometry (LC/MS/MS) with electrospray ionization in positive mode and a stable isotope (13C6)-labeled ABR-215062 as internal standard for calibration. The selected reaction monitoring was based on the transitions m/z 357.1 --> 236.1 for ABR-215062, and either m/z 363.2 --> 236.1 or 365.2 --> 238.1 for 13C6-ABR-215062. Method 1, aimed and validated for low level determinations (0.4-100 nmol/L) of ABR-215062, utilizes solid-phase extraction followed by isocratic elution. Method 2, aimed and validated for wide range determinations (0.75-15000 nmol/L) of ABR-215062, utilizes protein precipitation followed by fast gradient elution. The methods were validated with respect to selectivity, lower limit of quantification (LLOQ), dynamic range, precision, accuracy, extraction recovery and ruggedness. Furthermore, the stability of low level ABR-215062 in plasma was investigated. The methods were also applied in clinical trials. The LLOQs were 0.4 and 0.75 nmol/L for methods 1 and 2, respectively. The intra- and inter-day precision for the methods were 1.6-3.5% and 2.1-5.7%. The extraction recoveries were 90-97% for both methods. ABR-215062 was stable in plasma for at least 3 months when stored at -20 degrees C. In conclusion, our developed methods were found to be selective, sensitive, robust and suitable for applications in clinical pharmacokinetic profiling.

Chromatography, High Pressure Liquid↗

FIA-fluorimetric determination of the pesticide 3-indolyl acetic acid.

The paper presents the determination of the pesticide 3-indolyl acetic acid based on its native fluorescence; the method has been optimised either in a flow injection analysis (FIA) assembly or in batch. Maximum fluorescence intensity was observed at basic pH solutions at lambda(exc) = 280 nm and lambda(em) = 364 nm. The influence of different empirical parameters as pH, surfactants presence, solvent polarity, solved oxygen amount, and temperature was studied; highest outputs only required the pH in aqueous solutions to be adjusted over the range 9.5-10.5. Different calibration ranges were obtained by working with three different sensitivity scales of the fluorimeter either in flow injection analysis or batch. With the high sensitivity scale and FIA, the linear dynamic range was from 0.005 to 0.6 mg L(-1) 3-indolyl acetic acid; with an relative standard deviation (RSD) of 4.9% inter-day reproducibility. A large series of potential interferents was studied and finally, the method was applied to several water samples.

Buffers↗

Enhancing micro-scale membrane extraction by implementing a barrier film.

Hollow fiber based microextraction techniques have shown much promise in the extraction and preconcentration of analytes. Typically, a solvent held in the membrane is used as an extractant (or an acceptor). However, the acceptor also permeates out during long extractions and vigorous agitation. The stabilization of the acceptor is important for high enrichment and good reproducibility. Coating the membrane with a low permeability barrier film can provide diffusional resistance to reduce the outflow of the acceptor. Several compounds were evaluated as potential barrier films. They were found to protect the organic acceptor and significantly enhance extraction performance. In a study with six polycyclic aromatic hydrocarbons (PAHs), enrichment factors ranged between 494 and 4555 were obtained and the detection limits were at low ppb to ppt levels. Good reproducibility with RSDs between 1.60 and 7.65%, and large linear dynamic ranges with good linearity (R2 between 0.9870 and 0.9997) were also achieved.

Chemical Fractionation↗

Validation of a liquid chromatography-mass spectrometry multi-residue method for the simultaneous determination of sulfonamides, tetracyclines, and pyrimethamine in milk.

A multiresidue method suitable for confirmation and determination of six sulfonamides (SAs), three tetracyclines (TCs), and pyrimethamine (PYR) in cow milk was validated. Milk samples were extracted using copolymer Oasis HLB solid-phase extraction (SPE) and analyzed by liquid chromatography-electrospray mass spectrometry with positive ion mode. Estimated method detection limits (MDL) and method quantitation limits (MQL) ranged from 0.48 to 2.64 and 0.61 to 8.64ng/mL, respectively. These values are far lower than the maximum residue limits (MRLs) established by several control authorities. Excellent linear dynamic range was observed from the method quantitation limits to 300ng/mL with correlation coefficients better than 0.9900 for all compounds. The method was accurate with recoveries ranging from 72.01 to 97.39%. Good intra-precision and intermediate precision were obtained with RSD better than 11.08%. The method is fairly robust with sample pH being the only critical control point.

Animals↗

Pitch estimation of a deeply inserted cochlear implant electrode.

In this short communication, we evaluate the place-pitch relation of a newly designed, deeply inserted, cochlear implant electrode. The insertion depths ranged from 471 degrees to 662 degrees. Pitch perception was measured in eight subjects with monopolar stimulation on each electrode contact at intensities of 50% and 80% of the dynamic range. We observed a monotonic reduction of pitch estimate with insertion depth. For about half of the subjects, a flattening of the pitch estimate at the basal end of the electrode was seen, while for the other half, pitch continued to decrease monotonically up to the most apical part of the array. We conclude that deeper insertion could increase pitch range for at least some cochlear implant recipients, and could hence potentially increase group performance.

Adult↗

[Effect of intermittent photostimulation of varying frequency on the formation of trace processes and spectral components in the human EEG].

The EEG of occipital areas was recorded in adult healthy male subjects on presentation of haphazardly alternating intermittent light stimuli with frequencies varying from 15 to 5 Hz and from 15 to 25 Hz every 5 sec. Two groups were distinguished in respect to a greater or lesser domineering of the main frequency band of the range. Dynamic spectral analysis revealed obvious shifts of the EEG spectral composition in respect to the background under the effect of the stimulation, an enhancement of different bands of the range in light flickering, and the suppression of the EEG trace responses to the time in the EEG range coinciding in frequency with the frequency range of the photostimulation. The above changes were mainly characteristic of the 2nd group of subjects and mostly of the left hemisphere of the brain.

Adult↗

Dynamics imaging of lipid phases and lipid-marker interactions in model biomembranes.

Biomembranes are complex systems that regulate numerous biological processes. Lipid phases that constitute these membranes influence their properties and transport characteristics. Here, we demonstrate the potential of short-range dynamics imaging (excited-state lifetime, rotational diffusion, and order parameter) as a sensitive probe of lipid phases in giant unilamellar vesicles (GUVs). Liquid-disordered and gel phases were labeled with Bodipy-PC at room temperature. Two-photon fluorescence lifetime imaging microscopy of single-phase GUVs reveals more heterogeneity in fluorescence lifetimes of Bodipy in the gel phase (DPPC: 3.8+/-0.6 ns) as compared with the fluid phase (DOPC: 5.2+/-0.2 ns). The phase-specificity of excited-state lifetime of Bodipy-PC is attributed to the stacking of ordered lipid molecules that possibly enhances homo-FRET. Fluorescence polarization anisotropy imaging also reveals distinctive molecular order that is phase specific. The results are compared with DiI-C12-labeled fluid GUVs to investigate the sensitivity of our fluorescence dynamics assay to different lipid-marker interactions. Our results provide a molecular perspective of lipid phase dynamics and the nature of their microenvironments that will ultimately help our understanding of the structure-function relationship of biomembranes in vivo. Furthermore, these ultrafast excited-state dynamics will be used for molecular dynamics simulation of lipid-lipid, lipid-marker and lipid-protein interactions.

Anisotropy↗