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PubMed2005

Electrospray interfacing of polymer microfluidics to MALDI-MS.

The off-line coupling of polymer microfluidics to MALDI-MS is presented using electrospray deposition. Using polycarbonate microfluidic chips with integrated hydrophobic membrane electrospray tips, peptides and proteins are deposited onto a stainless steel target followed by MALDI-MS analysis. Microchip electrospray deposition is found to yield excellent spatial control and homogeneity of deposited peptide spots, and significantly improved MALDI-MS spectral reproducibility compared to traditional target preparation methods. A detection limit of 3.5 fmol is demonstrated for angiotensin. Furthermore, multiple electrospray tips on a single chip provide the ability to simultaneously elute parallel sample streams onto a MALDI target for high-throughput multiplexed analysis. Using a three-element electrospray tip array with 150 microm spacing, the simultaneous deposition of bradykinin, fibrinopeptide, and angiotensin is achieved with no cross talk between deposited samples. In addition, in-line proteolytic digestion of intact proteins is successfully achieved during the electrospray process by binding trypsin within the electrospray membrane, eliminating the need for on-probe digestion prior to MALDI-MS. The technology offers promise for a range of microfluidic platforms designed for high-throughput multiplexed proteomic analyses in which simultaneous on-chip separations require an effective interface to MS.

Microfluidic Analytical Techniques↗

PubMed2000

The reliability of balance tests performed on the kinesthetic ability trainer (KAT 2000).

The Kinesthetic Ability Trainer (KAT 2000) is a balance platform designed for training and functional testing of the neuromuscular control system. Forty healthy and sports-active persons were tested and 1 month later retested to investigate the reliability of the KAT 2000 testing "one-leg static balance" and "two-leg dynamic balance". A significant improvement at retesting on the same day was seen in both tests; furthermore the dynamic test result improved significantly with retesting 1 month later. The data obtained made it possible to calculate the 95% confidence limits for an unchanged test result for a single person and a group of persons. The results show a clear learning effect when the persons are retested, especially in the dynamic test. The KAT 2000 can be used as a tool for testing groups of persons both in short- and long-term studies, but it cannot be used for testing single persons due to the great variance in the test results. Further investigations involving injured persons are needed to determine the range of improvement after intervention.

Adolescent↗

PubMed2005

Evaluation of an Interactive Case-based Online Network (ICON) in a problem based learning environment.

PURPOSE: This study sought to assess the introduction of a web-based innovation in medical education that complements traditional problem-based learning curricula. Utilizing the case method as its fundamental educational approach, the Interactive Case-based Online Network (ICON) allows students to interact with each other, faculty and a virtual patient in difficult neurological cases. Given the paucity of available metrics to benchmark online systems, we complement user perceptions with data on system utilization. METHODS: We describe a case study of distinct, small group tutorials over 2 years as part of the Human Nervous System and Behavior (HNSB) course at the Harvard Medical School. Participating students and faculty were interviewed following completion of the course and their utilization of the system was recorded and examined. RESULTS: Students each spent 3.2+/-1.3 h (mean+/-SD) through 8.6+/-2.8 accessions per week using ICON outside of required tutorial time. Faculty each spent 4.8+/-3.4 h through 16.6+/-8.9 accessions per week on ICON. Students identified real-time engagement, stronger relationships with faculty, increased accountability to the tutorial group and self-selected pace as the most beneficial characteristics of the ICON-based tutorial in comparison to traditional problem based learning (PBL) tutorials. Faculty identified enhanced collaboration with students and more realistic student experiences as the most beneficial characteristics. Both students and faculty reported that limitations of ICON included increased time investment for faculty and increased reliance on good faculty mentorship. CONCLUSION: This is the first study of the ICON learning system in undergraduate medical education, a platform designed to facilitate collaboration outside of the classroom. Data on user perceptions and system utilization suggest that both faculty and students chose to adopt this online learning system as a means for collaboration. The study also outlines future avenues for research in assessing novel online technologies.

Computers↗

PubMedDate not supplied

Control and regulatory mechanisms associated with thermogenesis in flying insects and birds.

Most insects and birds are able to fly. The chitin made exoskeleton of insects poses them several constraints, and this is one the reasons they are in general small sized animals. On the other hand, because birds possess an endoskeleton made of bones they may grow much larger when compared to insects. The two taxa are quite different with regards to their general "design" platform, in particular with respect to their respiratory and circulatory systems. However, because they fly, they may share in common several traits, namely those associated with the control and regulatory mechanisms governing thermogenesis. High core temperatures are essential for animal flight irrespective of the taxa they belong to. Birds and insects have thus evolved mechanisms which allowed them to control and regulate high rates of heat fluxes. This article discusses possible convergent thermogenic control and regulatory mechanisms associated with flight in insects and birds.

Adipose Tissue, Brown↗

PubMed2006

Rotating platform knees: an emerging clinical standard: in opposition.

As surgeons, we share the common goals of making total knee arthroplasty as reliable, as reproducible, and as durable as we can. For that reason, we are almost compelled to investigate the rotating platform knee because of the contentions that it might improve patellar tracking, decrease lateral release rates, improve flexion, or perhaps give better wear characteristics over the long term. But when we take a step back and carefully examine the scientific data from 20 years of clinical experience with the rotating platform knee, the data speak for itself. To date, there are no demonstrated clinical advantages in regard to wear, survivorship, kinematics, range of motion, or patellar function. The rotating platform design then is really just another knee design, clinically indistinguishable from many well-functioning, fixed-bearing total knee designs.

Arthroplasty, Replacement, Knee↗

PubMed2004

Passive tactile sensibility in edentulous subjects treated with dental implants: a pilot study.

STATEMENT OF PROBLEM: Edentulous patients treated with implant-supported prostheses have shown increased passive tactile sensibility compared with those using conventional complete dentures. This is thought to be due to the close mechanical coupling between the implant and bone via the osseointegrated interface, yet the phenomenon has received little attention. PURPOSE: The purpose of this study was to measure passive tactile sensibility in a group of edentulous subjects treated with dental implants, and to relate the measured sensibility to a range of factors thought to be of possible relevance, namely, patient age, gender, time since implant placement, implant length, and implant separation. MATERIAL AND METHODS: Twenty edentulous subjects successfully treated with 2 or more Nobel Biocare dental implants in the anterior mandible were studied. The inclusion criteria were : (1) age of less than 50 years, (2) a period of at least 12 months since implant placement, (3) implant length of at least 10 mm and of standard diameter (excluding narrow and wide platform designs), and (4) implant separation of at least 18 mm. Using a computer-controlled custom-made device, pushing forces (2.1, 2.4, 2.7, and 3.0 N/s) were applied directly and perpendicular to the long axes of the implant abutments until the subjects felt the first sensation of pressure. The magnitude of these forces was measured with an integral transducer. The applied force had a ramped staircase pattern, and force application rates were varied between 2.1 and 3.0 N/s. Multilevel modeling was used to analyze the collected data (alpha=.05). RESULTS: The threshold values of passive tactile sensibility ranged between 3.1 and 15.7 N (mean 10.9; SD 3.9). Analysis failed to show any significant association between passive tactile sensibility and the variables studied. CONCLUSION: Within the limitations of this study, which included a small sample size, no relationship was found between passive tactile sensibility associated with long-standing implants and any of the variables studied (age, gender, time since implant placement, implant length, and implant separation).

Age Factors↗

PubMed1998

A method for in-situ tight-seal recordings from single taste bud cells of mice.

In order to investigate taste transduction mechanisms, we developed a method to irrigate the receptor and basolateral membranes of mouse taste bud cells with different solutions under tight-seal recording conditions. A peeled tongue epithelium with taste bud cells was mounted on a recording platform designed to separate irrigating solutions for each membrane. The mucosal surface (receptor membrane side) of the peeled epithelium facing an inner chamber was always irrigated with deionized water or stimulating solutions, and the serosal surface (basolateral membrane side) was irrigated with a physiological saline solution. A recording electrode was placed on the basolateral membrane of a taste bud cell under an upright-microscope with a x 40-water-immersed objective. Investigated taste bud cells generated action potentials, and 1 M glucose, 200 mM NaCl, and 10 mM quinine elicited inward current. Irrigation with deionized water for more than 1 h had no effect. The resistance of the peeled tongue epithelium was 1570 +/- 343 omega cm2. These results show that the peeled tongue epithelium protects basolateral membranes from deionized water or stimulating solutions as the tongue epithelium does in situ and that this method is suitable to investigate the role of each membrane in taste transduction.

Action Potentials↗

PubMedDate not supplied

Wear of fixed bearing and rotating platform mobile bearing knees subjected to high levels of internal and external tibial rotation.

In order to extend the lifetime of total knee replacements (TKR) in vivo, reduction of the volumetric wear rate of ultra high molecular weight polyethylene (UHMWPE) bearings remains an important goal. The volume of wear debris generated in fixed bearing total knee devices increases significantly when subjected to higher levels of internal-external rotation and anterior-posterior displacement. Six PFC Sigma fixed bearing TKR were compared with six LCS rotating platform mobile bearing knees using a physiological knee simulator with high rotation kinematic inputs. The rotating platform polyethylene inserts exhibited a mean wear rate which was one-third of that of the fixed bearing inserts despite having increased femoral contact areas and additional tibial wear surfaces. The rotating platform design decouples knee motions, by allowing unidirectional motion at the tray-insert articulation, which reduces rotation at the femoral-insert counterface. This translation of complex knee motions into more unidirectional motions results in molecular orientation of the UHMWPE and reduced volumetric wear.

Journal Article↗

PubMed1991

The influence of cadence and power output on the biomechanics of force application during steady-rate cycling in competitive and recreational cyclists.

The intent of this study was two-fold. The first aim was to investigate how cyclists orient forces applied by the feet to the pedals in response to varying power output and cadence demands, and the second was to assess whether competitive riders responded differently from recreational riders to such variations. One group consisted of US Cycling Federation category II licensed competitive cyclists (n = 7) and the second group consisted of recreational cyclists with no competitive experience (n = 38). The subjects rode an instrumented stationary 10-speed geared bicycle mounted on a platform designed to provide rolling and inertial resistance for six pedal rate/power output conditions for a minimum of 2 min for each ride. The pedalling rates were 60, 80 and 100 rev min-1 and the power outputs 100 and 235 W. All rides were presented in random order. The forces applied to the pedals, the pedal angle with respect to the crank and the crank angle were recorded for the final 30 s of each ride. From these data, a number of variables were computed including peak normal and tangential forces, crank torque, angular impulse, proportion of resultant force perpendicular to the crank, and pedal angle. Both the competitive and recreational groups responded similarly to increases in cadence and power output. There was a decrease in the peak normal forces, whereas the tangential component remained almost constant as cadence was increased. Regardless of cadence, the riders responded to increased power output demands by increasing the amount of positive angular impulse. All the riders had a reduced index of effectiveness as cadence increased. This was found to be the result of the large effect of the forces during recovery on this calculation. There were no significant differences between the two groups in each of these variables over all conditions. It was concluded that the lack of difference between the groups was a combined consequence of the limited degrees of freedom associated with the bicycle and that the relatively low power output for the competitive riders was insufficient to discriminate or highlight superior riding technique.

Adolescent↗

PubMed2026

SpacerScope: binary-vectorized, genome-wide off-target profiling for RNA-guided nucleases without prior candidate-site bias.

The precision of CRISPR/Cas systems is fundamental to their application in plant and animal biotechnology. However, comprehensive sequence-based off-target candidate discovery remains a computational bottleneck, particularly in large and complex genomes. Here we developed SpacerScope, an off-target candidate discovery framework that enables unbiased, genome-wide discovery by leveraging binary vectorization, bitwise filtering, and right-end-anchored alignment. Benchmarking against human CIRCLE-seq data demonstrated that SpacerScope recovered 100% of validated off-target sites (6142/6142), matching the sensitivity of exhaustive algorithms. Crucially, SpacerScope achieved this maximum candidate recovery while substantially reducing computational overhead. In large-genome evaluations, SpacerScope maintained low peak memory usage of 2.20 GiB and achieved substantial runtime improvements over indel-aware comparator tools, including more than 50-fold speedup relative to Cas-OFFinder 3 (544 s versus 29 185 s). Furthermore, comparative analyses in polyploid species, such as the octoploid strawberry, revealed that SpacerScope identified larger sequence-compatible candidate burdens than standard web-based design platforms. Our results establish SpacerScope as a high-speed framework for sequence-based genome-wide off-target candidate discovery across diverse and highly repetitive genomic landscapes. The source code and program was publicly available at https://github.com/charlesqu666/SpacerScope. Short Abstract CRISPR/Cas sequence-based off-target candidate discovery remains computationally challenging in large, repetitive, and polyploid genomes. Existing tools either miss indel-containing candidate sites or incur prohibitive runtime and memory costs. We developed SpacerScope, a binary-vectorized framework that enables unbiased, genome-wide off-target candidate discovery without pre-selected candidate sites. By integrating bitwise filtering with right-end-anchored alignment, SpacerScope recovered 100% of validated off-target sites in human CIRCLE-seq data while using only 2.20 GiB of memory and achieving more than 10-fold speedup over indel-aware alternatives. Evaluation in plant genomes, including rice and octoploid strawberry, further demonstrated SpacerScope's capacity to identify larger sequence-compatible candidate burdens overlooked by standard tools. SpacerScope thus provides a high-speed framework for sequence-based genome-wide off-target candidate discovery across diverse and highly repetitive genomic landscapes, supporting downstream prioritization.

CRISPR-Cas Systems↗

PubMed2026

OmicsQ: a user-friendly platform for interactive quantitative omics data analysis.

MOTIVATION: High-throughput omics technologies generate complex datasets with thousands of features that are quantified across multiple experimental conditions, but often suffer from incomplete measurements, missing values, and individually fluctuating variances. This requires analytical tools for accurate, deep and insightful biological interpretation, capable of dealing with a large variety of data properties and different amounts of completeness. Software capable of handling such data complexity and integrating with external applications for downstream analysis remains rare and mostly relies on programming-based environments, limiting accessibility for researchers without computational expertise. RESULTS: We present OmicsQ, an interactive, web-based platform designed to streamline quantitative omics data analysis. OmicsQ provides an intuitive, browser-based visualization interface that integrates established statistical processing tools. Those include robust batch correction, automated experimental design annotation, and handling of missing data without imputation, which maintains data integrity and avoids artifacts from a priori assumptions. OmicsQ seamlessly interacts with external applications (e.g. PolySTest, VSClust, ComplexBrowser) for statistical testing, clustering, analysis of protein complex behavior, and pathway enrichment, offering a comprehensive and flexible workflow from data import to biological interpretation that is broadly applicable across domains. AVAILABILITY AND IMPLEMENTATION: OmicsQ is implemented in R and Shiny and is available at https://computproteomics.bmb.sdu.dk/app_direct/OmicsQ. Source code and installation instructions: https://github.com/computproteomics/OmicsQ, DOI: 10.5281/zenodo.17778420.

Software↗

PubMed1986

Head position trainer application for research and clinical use.

The head position trainer (HPT) is a frequently used biofeedback device for improving the head control of cerebral palsied children. When the HPT is used as a training or evaluative device, questions may arise regarding the consistency and accuracy of positioning it on the head and the position of the trainee's head. This article describes a technique for positioning and orienting the head and the HPT to one another and to common axes. With the subject in a supine position on a specially designed platform, the long axes of the zygomatic arch and the control box of the HPT were oriented vertically. The headband of the HPT then was tightened about the midforehead and the occipital areas. Reference marks were made on the forehead and the HPT was removed. After the subject assumed the sitting position, the HPT was reapplied using the forehead reference marks and the occipital areas as guides. Test-retest procedures were conducted using different therapists to apply the HPT to healthy and to handicapped subjects. The criterion score was the degrees difference between the long axes of the HPT control box and the zygomatic arch, an angle that would be 0 degree if the two long axes were parallel. No significant differences were observed between Trials 1 and 2, and the correlation coefficient between the two trials was statistically significant (p less than .02) in all situations. The HPT referencing platform can be constructed at minimal expense, and the technique of HPT application is relatively quick and reliable, and it produces minimal stress in handicapped subjects.

Adult↗

PubMedDate not supplied

Accuracy of volume measurement using helical CT.

PURPOSE: Our goal was to determine the accuracy of volume estimation using helical CT. METHOD: Helical CT scans were conducted with regularly and irregularly shaped polyvinylchloride bags containing saline of varying volumes immersed in peanut oil during various rates of movement of 0, 10, 15, and 20 cycles/min, using a motorized platform, designed to simulate respiratory motion. Ten cancer patients were scanned with CT to determine optimum upper and lower Hounsfield unit thresholds. The volumes of two human livers and kidneys were also measured in vitro under the same conditions. RESULTS: For all conditions, the accuracy and bias of volume estimation for saline bags ranged from 95.0 to 99.2 and -3.46 to 4.04%, respectively, and the accuracy and bias for the estimation of liver and kidney volumes were 95.6 and 3.12%, respectively. CONCLUSION: This study shows that helical CT is a highly accurate technique for estimating volume, even in the presence of simulated respiratory motion.

Humans↗

PubMed2003

Effect of putting grip on eye and head movements during the golf putting stroke.

The objective of this article is to determine the effect of three different putting grips (conventional, cross-hand, and one-handed) on variations in eye and head movements during the putting stroke. Seven volunteer novice players, ranging in age from 21 to 22 years, participated in the study. During each experimental session, the subject stood on a specially designed platform covered with artificial turf and putted golf balls towards a standard golf hole. The three different types of grips were tested at two distances: 3 and 9 ft. For each condition, 20 putts were attempted. For each putt, data were recorded over a 3-s interval at a sampling rate of 100 Hz. Eye movements were recorded using a helmet-mounted eye movement monitor. Head rotation about an imaginary axis through the top of the head and its center-of-rotation was measured by means of a potentiometer mounted on a fixed frame and coupled to the helmet. Putter-head motion was measured using a linear array of infrared phototransistors embedded in the platform. The standard deviation (STD, relative to the initial level) was calculated for eye and head movements over the duration of the putt (i.e., from the beginning of the backstroke, through the forward stroke, to impact). The averaged STD for the attempted putts was calculated for each subject. Then, the averaged STDs and other data for the seven subjects were statistically compared across the three grip conditions. The STD of eye movements were greater (p < 0.1) for conventional than cross-hand (9 ft) and one-handed (3 and 9 ft) grips. Also, the STD of head movements were greater (p < 0.1; 3 ft) for conventional than cross-hand and one-handed grips. Vestibulo-ocular responses associated with head rotations could be observed in many 9 ft and some 3 ft putts. The duration of the putt was significantly longer (p < 0.05; 3 and 9 ft) for the one-handed than conventional and cross-hand grips. Finally, performance, or percentage putts made, was significantly better (p < 0.05; 9 ft) for cross-hand than conventional grip. The smaller variations, both in eye movements during longer putts and head movements during shorter putts, using cross-hand and one-handed grips may explain why some golfers, based on their playing experience, prefer these over the conventional grip. Also, the longer duration for the one-handed grip, which improves tempo, may explain why some senior players prefer the long-shaft (effectively one-handed grip) putter.

Adult↗

PubMed1995

A database of cardiac arrhythmias.

OBJECTIVE: To describe a database of cardiac arrhythmia recordings, useful for the development and testing of ECG rhythm processing or monitoring algorithms and devices. METHODS: The raw data were acquired within the Wisconsin-Dane County emergency medical technician-defibrillation program and contained emergency rhythm recordings of an average length of 30 minutes. The raw data were integrated into a software platform designed for the annotation and visualization of the recordings. RESULTS: Currently the database contains the following arrhythmia episodes: ventricular fibrillation (56), asystole (65), electromechanical dissociation (31), and other arrhythmias (42). The software, resident on personal computers, also can transmit any of the database recordings, through a digital-to-analog converter board, to a device under test. CONCLUSIONS: The database technique described will provide a useful means of objectively assessing electronic devices for their ability to detect arrhythmias. The database is unique in that it contains lengthy episodes of arrhythmias. The database will be extended to include additional cases.

Arrhythmias, Cardiac↗

PubMed2001

Effects of heel and toe elevation upon the digital joint angles in the standing horse.

Five sound mature horses, age 8-14 years, with toe angles 45.5-55.0 degrees were placed on a specially designed platform with only the left forelimb weightbearing, which allowed the successive production of 7 different conditions of foot orientation: neutral position (N), 5, 10, 15 degrees heel (H5, H10, H15) and toe (T5, T10, T15) elevation, performed according to 2 different sequences. For each condition, 2 lateromedial radiographs were taken to evaluate the metacarpophalangeal joint (MPJ) and both interphalangeal joint (PIPJ and DIPJ) angles, respectively. In addition, two-dimensional (2-D) kinematic recordings, using reflective skin markers placed laterally on the left forelimb joints, were performed. The value of each joint angle (JA) and its angular variation to N (AV) were considered for statistical analysis. For all JA and their AV determined radiographically, the condition effect was significant and the sequence did not influence the differences between conditions. The relationships between the JA and the conditions (in the sequence: T15, T10, T5, N, H5, H10, H15) were overall linear for the 3 joints. The maximal range T15-H15 was mean +/- s.d. 6.9 +/- 2.0 degrees for MPJ (dorsal angle decrease), 7.3 +/- 1.0 degrees and 29.5 +/- 1.8 degrees for PIPJ and DIPJ (palmar angle decrease), respectively. Contrary to JA and in spite of large variations in hoof conformation, AV did not show any significant horse effect. Wide differences were observed between the digital JA measured radiographically and from kinematics, which could be related to cutaneous displacement. Heel elevation induced elbow flexion, whereas a slight extension was observed with toe elevation. These movements, even slight (mean elbow angle amplitude: 3.6 +/- 1.3 degrees), may have consequences upon flexor tendon tension.

Analysis of Variance↗

PubMed2003

Physiological control of pituitary hormone secretory-burst mass, frequency, and waveform: a statistical formulation and analysis.

The present study investigates the time-varying control of pituitary hormone secretion over the day and night (D/N). To this end, we implemented an analytical platform designed to reconstruct simultaneously 1) basal (nonpulsatile) secretion, 2) single or dual secretory-burst waveforms, 3) random effects on burst amplitude, 4) stochastic pulse-renewal properties, 5) biexponential elimination kinetics, and 6) experimental uncertainty. The statistical solution is conditioned on a priori pulse-onset times, which are estimated in the first stage. Primary data composed of thyrotropin (TSH) concentrations were monitored over 24 h in 27 healthy adults. According to statistical criteria, 21/27 profiles favored a dual compared with single secretory-burst waveform. An objectively defined waveform change point (D/N boundary) emerged at 2046 (+/-23 min), after which 1) the mass of TSH released per burst increases by 2.1-fold (P < 0.001), 2) TSH secretory-burst frequency rises by 1.2-fold (P < 0.001), 3) the latency to maximal TSH secretion within a burst decreases by 67% (P < 0.001), 4) variability in secretory-burst shape diminishes by 50% (P < 0.001), and 5) basal TSH secretion declines by 17% (P < 0.002). In contrast, the regularity of successive burst times and the slow-phase half-life are stable. In conclusion, nycthemeral mechanisms govern TSH secretory-burst mass, frequency, waveform, and variability but not evidently TSH elimination kinetics or the pulse-timing process. Further studies will be required to assess the generality of the foregoing distinctive control mechanisms in other hypothalamo-pituitary axes.

Adult↗

PubMed1989

A treadmill-mounted force platform.

Muscle, bone, and tendon forces; the movement of the center of mass, and the spring properties of the body during terrestrial locomotion can be measured using ground-mounted force platforms. These measurements have been extremely time consuming because of the difficulty in obtaining repeatable constant speed trials (particularly with animals). We have overcome this difficulty by mounting a force platform directly under the belt of a motorized treadmill. With this arrangement, vertical force can be recorded from an unlimited number of successive ground contacts in a much shorter time. With this treadmill-mounted force platform it is possible to accurately make the following measurements over the full range of steady speeds and under various perturbations of normal gait: 1) vertical ground reaction force over the course of the contact phase; 2) peak forces in bone, muscle, and tendon; 3) the vertical displacement of the center of mass; and 4) contact time for the limbs. In our treadmill-force platform design, belt forces and frictional forces cause no measurable cross-talk problem. Natural frequency (160 Hz), nonlinearity (less than 5%), and position independence (less than 2%) are all quite acceptable. Motor-caused vibrations are greater than 150 Hz and thus can be easily filtered.

Biomechanical Phenomena↗