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Micro gradient-index conical lenses: simulation and fabrication methods.

In this paper, a micro gradient-index conical lens, which has a larger acceptance angle than a conventional microlens, is presented. Methods on how to simulate these lenses in commercial optical design software CodeV are introduced, and the effects of several index profiles and cone shapes are compared in simulation. Results show that a micro gradient-index conical lens has a four times larger acceptance angle compared with a microlens. Additionally, conical lenses with a Gaussian-index profile show a larger acceptance angle than those with a solid refractive index. Fabricated conical lenses show an acceptance angle of more than 27 degrees for a detection threshold of 50%, which agrees with the simulation result.

Journal Article↗

Zoom lens design for a novel imaging spectrometer that controls spatial and spectral resolution individually.

A novel imaging spectrometer can individually control spatial and spectral resolution by using zoom lenses as the foreoptics of the system and a focusing lens. By varying the focal length we can use the focusing lens to change the spatial and spectral dimensions; with the foreoptics, however, we can change only the spatial dimension. Therefore the spectral resolution and the spectral range are affected by the zoom ratio of the focusing lens, whereas the spatial resolution and the field of view are affected by the multiplication of the zoom ratios of the foreoptics and the focusing lens. By properly combining two zoom ratios, we can control the spectral resolution with a fixed spatial resolution or the spatial resolution with a fixed spectral resolution. For an imaging spectrometer with this novel zooming function, we used the lens module method and third-order aberration theory to design an initial four-group zoom system with an external entrance pupil for the focusing lens. Furthermore, using the optical design software CODE V, we obtained an optimized zoom lens with a focal-length range of 50 to 150 mm. Finally, the zoom system with its transmission grating in the Littrow configuration performs satisfactorily as the focusing lens of an imaging spectrometer in the wavelength range 450-900 nm.

Journal Article↗

Power coupled between partially coherent vector fields in different states of coherence.

A procedure is described for calculating the power coupled between collimated, partially coherent vector fields that are in different states of coherence. This topic is of considerable importance in designing submillimeter-wave optical systems for astronomy. It is shown that if the incoming field S has coherence matrix A, and the outgoing field D has coherence matrix B, then the power coupled is simply Ps = Tr(ATBT), where the elements of T project the basis functions of B onto those of A. A similar technique can be used to calculate the power coupled from the background of S to D. The scheme is illustrated by calculating the power coupled between two scalar, Gaussian Schell-model beams. The procedure can be incorporated into optical design software.

Journal Article↗

Use of self-quenched, fluorogenic LUX primers for gene expression profiling.

Application of a real-time detection system based on a novel primer design in gene expression profiling is described. In this system, called LUX (Light Upon eXtension), the generation of signal is based on a single fluorescent dye molecule that is attached to an oligonucleotide close to the 3'-end. A primer design software is available that identifies LUX primer pairs based on a set of rules for optimum signal development. The use of LUX fluorogenic primers to determine the expression patterns of various transcripts during differentiation in the P-19 mouse neuronal model is described.

Animals↗

[Cardiac pacemaker as bridge to cardiac telemonitoring].

Modern pacemakers and electrodes are equipped with supplementary features that can be utilized for many problems related to cardiac diagnosis and therapy management. Especially the recording and computer-assisted analysis of intramyocardial electrograms (IEGM), particularly of ventricular evoked responses (VER), supplies important information. The IEGMs are transmitted with large bandwidth from the implanted pacemaker to an extracorporeal receiver and from there via Internet to a central data processing station, where a specially designed software for IEGM processing is available. An individual password secured account is installed for each user. After signal processing is completed, a comprehensive patient report including trend courses and relevant clinical data is provided and can be utilized by the user for further decisions. Using this basic structure, CHARM (Computerized Heart Acute Rejection Monitoring), a system for non-invasive rejection monitoring after heart transplantation, has been developed and successfully evaluated in a clinical environment.

Computer Systems↗

Backbone dynamics of a symmetric calmodulin dimer in complex with the calmodulin-binding domain of the basic-helix-loop-helix transcription factor SEF2-1/E2-2: a highly dynamic complex.

Calmodulin (CaM) interacts specifically as a dimer with some dimeric basic-Helix-Loop-Helix (bHLH) transcription factors via a novel high affinity binding mode. Here we report a study of the backbone dynamics by (15)N-spin relaxation on the CaM dimer in complex with a dimeric peptide that mimics the CaM binding region of the bHLH transcription factor SEF2-1. The relaxation data were measured at multiple magnetic fields, and analyzed in a model-free manner using in-house written software designed to detect nanosecond internal motion. Besides picosecond motions, all residues also experience internal motion with an effective correlation time of approximately 2.5 ns with squared order parameter (S(2)) of approximately 0.75. Hydrodynamic calculations suggest that this can be attributed to motions of the N- and C-terminal domains of the CaM dimer in the complex. Moreover, residues with significant exchange broadening are found. They are clustered in the CaM:SEF2-1mp binding interface, the CaM:CaM dimer interface, and in the flexible helix connecting the CaM N- and C-terminal domains, and have similar exchange times (approximately 50 micros), suggesting a cooperative mechanism probably caused by protein:protein interactions. The dynamic features presented here support the conclusion that the conformationally heterogeneous bHLH mimicking peptide trapped inside the CaM dimer exchanges between different binding sites on both nanosecond and microsecond timescales. Nature has thus found a way to specifically recognize a relatively ill-fitting target. This novel mode of target-specific binding, which neither belongs to lock-and-key nor induced-fit binding, is characterized by dimerization and continuous exchange between multiple flexible binding alternatives.

Binding Sites↗

Image-shifting optics for a nystagmus treatment device.

Acquired pendular nystagmus (APN) complicates multiple sclerosis and other neurological disorders, causes visual impairment, and is often refractory to available treatments. Vision could be improved by an optical aid that shifts the seen world in lockstep with the APN. An essential component of such a device is the image-shifting mechanism, which must be light, accurate, suitable for battery operation, and capable of image shifting at the frequencies and amplitudes seen in APN. We determined that a three-lens image-shifting mechanism used in commercial image-stabilizing lenses has the potential to satisfy all these requirements. In combination with software designed to track nystagmus, the optical mechanism proved capable of improving visual acuity in 12 normal subjects experiencing simulated two-dimensional nystagmus. Acuity was restored to within an average of 0.12 logMAR (range 0.0-0.22) of the subjects' values without the simulated nystagmus. These results support the feasibility of an assistive device for patients with APN.

Adaptation, Physiological↗

The effect of hyaluronan on bone and soft tissue and immune response in wound healing.

BACKGROUND: The aims of this study were to investigate the anti-inflammatory effect and the effect on bone regeneration of hyaluronan in surgical and non-surgical groups. METHODS: In each of 15 individuals, 2 teeth with defects of similar character and magnitude in the upper or lower jaw were chosen. There were at least 2 teeth between the test and the control sites. In the surgical group, a bioabsorbable membrane was used for both test and control sites, and hyaluronan was placed in the intrabony pocket of the test site. In the non-surgical group, the periodontal pockets were scaled and hyaluronan was administered 3 times with an interval of 1 week in the test pockets. Alveolar bone height and bone healing patterns were analyzed using digital intraoral radiographs. Measurements of bone height were performed in the original digital black-and-white radiographs to obtain quantitative data on bone gain or loss. Bone healing patterns were studied with color-coded radiographs, using specially designed software in a personal computer with subsequent combinations of radiographs. Gingival crevicular fluid immunoglobulin (Ig)G, C3, and prostaglandin E2 (PGE2) responses; periodontal probing depth; bleeding on probing; and the presence of plaque were studied to evaluate the anti-inflammatory effect. Data were obtained at baseline before treatment, and at 2 weeks, and 1, 3, 6, and 12 months after treatment. RESULTS: For the surgical treatments, bone height was increased in the test group treated with hyaluronan (mean value 2.2%, corresponding to an average increase of approximately 0.5 mm) and reduced in the control group (mean value -1.8%, corresponding to an average decrease of approximately - 0.4 mm) (P<0.05) after 12 months. For the non-surgical treatments, bone height was reduced by a mean value of -1.1% (corresponding to an average decrease of approximately -0.25 mm) in the test group treated with hyaluronan and -3.3% (corresponding to an average decrease of approximately -0.75 mm) in the control group after 12 months (N.S.). According to the digital color-coded radiographs, the test sites in the surgical and non-surgical groups showed apposition of bone minerals. Immune responses showed no differences during the 12 months studied for the surgical and non-surgical sites. Mean periodontal probing depths were reduced between 2.5 mm and 4.1 mm in the surgical and non-surgical groups. CONCLUSIONS: The observed difference in bone height between test and control sites in the surgical group after 12 months was less than 1 mm, which was only detectable on radiographs. No statistical difference was found on radiographs in the non-surgical group, where a decrease in bone height was found for both groups after scaling. Probing depth reduction after the surgical treatment, as well as after scaling and root planing, was as expected. Hyaluronan in contact with bone and soft tissues had no influence on the immune system in this study. Further studies are needed to determine the extent to which hyaluronan can lead to clinically significant healing of periodontal lesions.

Absorbable Implants↗

Comparison of handheld computer-assisted and conventional paper chart documentation of medical records. A randomized, controlled trial.

BACKGROUND: Daily documentation and maintenance of medical record quality is a crucial issue in orthopaedic surgery. The purpose of the present study was to determine whether the introduction of a handheld computer could improve both the quantitative and qualitative aspects of medical records. METHODS: A series of consecutive patients who were admitted for the first time to a thirty-six-bed orthopaedic ward of an academic teaching hospital for a planned operation or any other treatment of an acute injury or chronic condition were randomized to daily documentation of their clinical charts on a handheld computer or on conventional paper forms. The electronic documentation consisted of a specially designed software package on a handheld computer for bedside use with structured decision trees for examination, obtaining a history, and coding. In the control arm, chart notes were compiled on standard paper forms and were subsequently entered into the hospital's information system. The number of documented ICD (International Classification of Diseases) diagnoses was the primary end point for sample size calculations. All patient charts were reread by an expert panel consisting of two surgeons and the surgical quality assurance manager. These experts assigned quality ratings to the different documentation systems by scrutinizing the extent and accuracy of the patient histories and the physical findings as assessed by daily chart notes. RESULTS: Eighty patients were randomized to one of the two documentation arms, and seventy-eight (forty-seven men and thirty-one women) of them were eligible for final analysis. Documentation with the handheld computer increased the median number of diagnoses per patients from four to nine (p < 0.0001), but it produced some overcoding for false or redundant items. Documentation quality ratings improved significantly with the introduction of the handheld device (p < 0.01) with respect to the correct assessment of a patient's progress and translation into ICD diagnoses. Various learning curve effects were observed with different operators. Study physicians assigned slightly better practicability ratings to the handheld device. CONCLUSIONS: The preliminary data from this study suggest that handheld computers may improve the quality of hospital charts in orthopaedic surgery. LEVEL OF EVIDENCE: Therapeutic study, Level I-1a (randomized controlled trial [significant difference]). See Instructions to Authors for a complete description of levels of evidence.

Adult↗

Development of a high-throughput process for detection and screening of genetic polymorphisms.

A method is described that uses the ABI PRISM 310 genetic analyzer in conjunction with custom-designed software to identify and classify RAPD products. This methodology will also work well with AFLPs and microsatellite analyses. The methodology uses the ABI PRISM 310's high-throughput (> 500 samples per week) capabilities and in-lane molecular weight standards to efficiently separate and size DNA products. Peak detection, locus classification and export of the data in a form accessible by several genetic analysis programs were accomplished through a custom-written software program (Peaks). Various criteria used by the program to identify and classify loci are described, and their effect on population analyses is examined. Criteria providing an effective, robust determination of population structure are presented.

Alleles↗

AutoDimer: a screening tool for primer-dimer and hairpin structures.

The ability to select short DNA oligonucleotide sequences capable of binding solely to their intended target is of great importance in developing nucleic acid based detection technologies. Applications such as multiplex PCR rely on primers binding to unique regions in a genome. Competing side reactions with other primer pairs or template DNA decrease PCR efficiency: Freely available primer design software such as Primer3 screens for potential hairpin and primer-dimer interactions while selecting a single primer pair. The development of multiplex PCR assays (in the range of 5 to 20 loci) requires the screening of all primer pairs for potential cross-reactivity. However, a logistical problem results due to the number of total number of comparisons required. Comparing the primer set for a 10-plex assay (20 total primer sequences) results in 210 primer-primer combinations that must be screened. The ability to screen sets of candidate oligomers rapidly for potential cross-reactivity reduces overall assay devlelopment time. Here we report the application of a familiar sliding algorithm for comparing two strands of DNA in an overlapping fashion. The algorithm has been employed in a software package wherein the user can compare multiple sequences in a single computational run. After the screening is completed, a score is assigned to potential duplex interactions exceeding a user-defined threshold. Additional criteria of predicted melting temperature (Tm) and free energy of melting (deltaG) are included for further ranking. Sodium counterion and total stand concentrations can be adjusted for the Tm and deltaG calculations. The predicted interactions are saved in a text file for further evaluation.

Algorithms↗

Automated multi-well device to measure transepithelial electrical resistances under physiological conditions.

Measurement of transendothelial or transepithelial electrical resistances (TERs) is a straightforward in situ experimental approach to monitor the expression or modulation of barrier-forming cell-to-cell contacts (tight junctions) in cultured cells grown on porous filters. Although widely accepted, there is currently no device available to automatically measure the time course of TERs under ordinary cell culture conditions (37 degrees C, 5% or 10% CO2). This paper describes a development from our laboratory that is capable of following in parallel the TERs of several filter-grown cell layers with time and in an entirely computer-controlled fashion. The cell cultures can be followed even in long-term experiments without any manual assistance or opening of the incubator Besides reading TER values, this approach also returns the electrical capacitance of the cell layers, which is indicative of the expression of microvilli and other membrane extrusions. The device is based on reading the frequencydependent impedance of the cell layer, followed by equivalent circuit modeling to extract the cell-related parameters. It is compatible with several multi-well formats (up to 96 wells) and controlled by custom-designed software that reads, analyzes, and presents the data.

Animals↗

An object-oriented programming system for the integration of internet-based bioinformatics resources.

The Internet consists of a vast inhomogeneous reservoir of data. Developing software that can integrate a wide variety of different data sources is a major challenge that must be addressed for the realisation of the full potential of the Internet as a scientific research tool. This article presents a semi-automated object-oriented programming system for integrating web-based resources. We demonstrate that the current Internet standards (HTML, CGI [common gateway interface], Java, etc.) can be exploited to develop a data retrieval system that scans existing web interfaces and then uses a set of rules to generate new Java code that can automatically retrieve data from the Web. The validity of the software has been demonstrated by testing it on several biological databases. We also examine the current limitations of the Internet and discuss the need for the development of universal standards for web-based data.

Computational Biology↗

The impact of pharmaceutical care practice on the practitioner and the patient in the ambulatory practice setting: twenty-five years of experience.

This manuscript reviews 25 years of experience that include developing the practice of pharmaceutical care and initiating new practices. The impact this practice has on practitioners in the ambulatory setting is described as well as data that reflect its clinical and economic impact. There is a great need to prepare new practitioners to provide pharmaceutical care. A focused training program was developed and delivered to over 300 practitioners. The practitioners were prepared by providing direct patient care. They learned the philosophy of pharmaceutical care practice, to identify, resolve and prevent drug therapy problems, to document care using a specially designed software program called the Assurance Pharmaceutical Care program. The practitioners who participated in the training program reported that the average amount of time spent with patients increased three-fold, they now see four times more patients than prior to training, and the number of new patients referred by physicians increased nine-fold as a result of the program. These practitioners have now provided care to more than 25,000 patients in their practices. These data have now been consolidated and analyzed, and a portion of these results is reported here. The clinical and economic outcomes from 2,985 adult patients, who received pharmaceutical care between January, 2000 and December, 2003, are presented. At the first assessment by the pharmaceutical care practitioner, 61% of the patients had one or more drug therapy problems identified and resolved. This resulted in an improvement in the clinical status or maintaining a stable status in 83% of the patients. The health care savings realized from pharmaceutical care were $1,134,162. This represented a benefit to cost ratio of 2:1. Physicians who collaborate with pharmaceutical care practitioners have validated the work of the practitioners, and patients are recognizing the benefits of pharmaceutical care.

Adult↗

Accelerometer-based body-position sensing for ambulatory electrocardiographic monitoring.

Our objective is to validate the ability of 3 appropriately placed accelerometers to determine body position during ambulatory electrocardiographic (ECG) monitoring and to demonstrate the clinical applicability of this method. During ambulatory (Holter) monitoring, the ability to know a patient's position (lying down, sitting, standing, or changing from one position to another) is important in the evaluation of common symptoms such as dizziness, palpitations, and syncope. Changes in body position are also known to alter the electrical axis of the heart, resulting in artifactual changes in QRS amplitude and ST-segment morphology. We have developed an ambulatory patient-monitoring instrument that, through the use of microfabricated accelerometers, can simultaneously record body-position information and 2 channels of ECG data. The accelerometers measure the effects of gravity and dynamic acceleration, allowing determination of a patient's orientation and movements. The accelerometer and ECG signals are input to a portable recorder and are filtered and digitized. Algorithms were developed to automatically determine body position. Ten healthy volunteers wore the device for 1 hour and followed a protocol of standing, sitting, walking, lying supine, and lying in the left and right lateral decubitus positions. An observer manually recorded times of position changes. Data were recorded and analyzed using software designed with MATLAB. The ability of the accelerometers and computer algorithms to determine body position was analyzed in terms of the sensitivity and specificity for each body position. The sensitivities for sitting, standing, walking, lying supine, lying right, and lying left were 98.8%, 99.2%, 95.5%, 99.1%, 98.9%, and 94.8%, respectively. The specificities were 99.7%, 99.4%, 99.6%, 99.0%, 99.8%, and 99.9%, respectively. The use of microfabricated accelerometers is a clinically feasible method to determine body position and can be applied to future studies correlating body position with ECG or other physiologic data.

Acceleration↗

Preferred sound intensity increase for sensation of half distance.

Two experiments are reported that examine the preferred increase in intensity for creating a percept of half auditory distance from a reference. The results of both experiments indicate that the use of an inverse square law (increments of 6 dB) is not the best signal-processing method for this purpose. The application of the results is potentially useful towards the software design of 3-D auditory display systems that manipulate the perceived distance of auditory inputs in relationships to actual distances of physical objects.

Adult↗

Body-size estimation by obese subjects.

The present aim was to explore the body-image perception of a group of 60 hospitalized obese subjects, aged between 25 and 50 years, undergoing a weight loss treatment and 60 normal-weight persons. The 1978 modified version of the Askevold perception test by Allamani, Marasco, Michele, and Morandi was given. This nonverbal test is aimed at evaluating subjects' perception of the dimensions of different parts of the body by exploiting their projection into space. Each body area (head, the thoracic area, the abdominal area, and the pelvic area) perceived by a subject was calculated using a specifically designed software program (AREA.BASIC2); the same program was used to calculate actual body area. After obtaining the percentage deviation index for each individual [(perceived area/real area) x 100], mean values were analyzed. Obese subjects significantly underestimated the four body areas, unlike the normal weight subject who largely overestimated the abdominal and pelvic areas.

Adult↗