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At least 181 records · Page 10Linked to original sources

PubMed2003

CRC Tissue Core Management System (TCMS): integration of basic science and clinical data for translational research.

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9 geographically distributed sites conducting a program of research including both basic science and clinical components. The CRC TCMS was designed to capture and integrate basic science and clinical data sets. The system utilizes multiple data modeling methodologies and web-application platforms, and was designed with the high level objectives of providing an extensible, generalizable model for integrating data as required to conduct translational research.

Biomedical Research↗

PubMed2004

Optimization of the antibody C(H)3 domain by residue frequency analysis of IgG sequences.

In an attempt to enhance the overall assembly, yield and half-life of recombinant antibody proteins, we have cloned and expressed several IgG1 C(H)3 domains and examined their folding/refolding characteristics. We utilized a cytoplasmic bacterial expression system with a thioredoxin reductase knock-out strain of BL21(DE3) to produce bovine, murine and human C(H)3. Under identical conditions, expression of bovine C(H)3 resulted consistently in the highest yields of properly folded/oxidized protein. Circular dichroism and fluorescence experiments demonstrate that oxidized bovine and murine C(H)3 have surprisingly similar structures and stabilities, considering the marginal sequence conservation between the two molecules. Residue frequency analysis using a limited data set of 36 unique Fc sequences originating from 19 different mammalian species targeted five specific sites for optimization within bovine C(H)3. Combination of three of these mutants increased the thermal stability of the molecule to 86 degrees C. Comparison of this approach to similar studies using larger sequence databases and/or different selection criteria suggests sequence database design can increase the success rate for identifying residue sites worth optimizing. This optimized C(H)3 domain can be used as a particularly stable platform for functional design and can be grafted into full-length antibody sequences to enhance their thermodynamic parameters and shelf-life.

Amino Acid Sequence↗

PubMed2004

Distributed collaborative CAD system based on Web Service.

This paper presents a novel Web Service based distributed collaborative CAD system employing feature as its collaborative design element and uses XML to define feature operations and communication protocol between the server and the client. To reduce network load and increase response ability of the system, the feature information is updated incrementally on the client. The system supports collaborative designing on heterogeneous platforms. Its framework and communication protocols are analyzed in detail. The experimental results from the developed prototype system showed that it can effectively support collaborative design under the distributed environment.

Journal Article↗

PubMed1998

Design, control, and characterization of a Sliding Linear Investigative Platform for Analyzing Lower Limb Stability (SLIP-FALLS).

A novel device, the Sliding Linear Investigative Platform For Analyzing Lower Limb Stability (SLIP-FALLS), has been designed to study the detection and discrimination thresholds of humans to uniaxial horizontal step, ramp, or sinusoidal translations of the surface upon which they stand or stride. The device also can be used to test the human potential for, and mechanisms of, slips and falls. The SLIP utilizes air bearing technology and a noncontact linear motor to produce ultra-low-vibration translations. The FALLS system measures the forces on four load cells, platform linear and head tri-axial accelerations, four channels of electromyographic data, motor voltage, and a subject's psychophysical response; and derives other physiological and biomechanical measures, like center-of-pressure and shear force. The effect of acceleration and shear force on the accuracy of the center-of-pressure calculations is presented. Operating ranges depend on the interactions among displacement, velocity, acceleration, and jerk parameters for linear translations, and between amplitudes and frequencies for sinusoidal translations. Displacements from 5 microm to 0.277 m, velocities from 5 microm/s to 0.3 m/s, and accelerations up to 2.5 m/s2 are achievable with precise control (i.e., without overshoot), but tradeoffs exist such that all three maxima cannot be reached simultaneously. For a 0.15 m/s linear translation at 4 m/s2, SLIP-FALLS produces substantially less vibration than the worm-driven NeuroTest system. The usefulness of having precise control over movement parameters is discussed.

Biomechanical Phenomena↗

PubMed2004

A front-end automation tool supporting design, verification and reuse of SOC.

This paper describes an in-house developed language tool called VPerl used in developing a 250 MHz 32-bit high-performance low power embedded CPU core. The authors showed that use of this tool can compress the Verilog code by more than a factor of 5, increase the efficiency of the front-end design, reduce the bug rate significantly. This tool can be used to enhance the reusability of an intellectual property model, and facilitate porting design for different platforms.

Algorithms↗

PubMed2005

Teaching real-time ultrasonic imaging with a 4-channel sonar array, TI C6711 DSK and MATLAB.

Ultrasonic medical imaging courses often stop at the theory or MATLAB simulation level, since professors find it challenging to give the students the experience of designing a real-time ultrasonic system. Some of the practical problems of working with real-time data from the ultrasonic transducers can be avoided by working at lower frequencies (sonar to low ultrasound) range. To facilitate this, we have created a platform using the ease of MATLAB programming with the real-time processing capability of the low-cost Texas Instruments C6711 DSP starter kit and a 4-channel sonar array. With this platform students can design a B-mode or Color-Mode sonar system in the MATLAB environment. This paper will demonstrate how the platform can be used in the classroom to demonstrate the real-time signal processing stages including beamforming, multi-rate sampling, demodulation, filtering, image processing, echo imaging, and Doppler frequency estimation.

Algorithms↗

PubMed2005

An electrochemical sensor array system for the direct, simultaneous in vitro monitoring of nitric oxide and superoxide production by cultured cells.

A new approach for an amperometric array sensor platform employing arrays of sensors in a 24-well cell culture plate format has been developed for simultaneous in vitro determination of nitric oxide (NO) and superoxide free radicals (O(2)(-)) produced by stimulated cells. The work reported focuses on the direct, real-time monitoring of extracellular production of these two analytes, as well as the effects of their interaction. The sensor platform was manufactured by a combination of sputtering gold electrodes and screen-printing carbon electrodes. The O(2)(-) sensor uses covalent immobilization of cytochrome c via a binder, DTSSP (3,3'-dithio-bis(sulphosuccinimidylpropionate) onto the surface of the Au electrodes, whereas the NO sensor system involves an NiTSPc (nickel tetrasulfonated phthalocyanine) film electrodeposited onto the surface of the carbon electrodes and subsequently covered with an external layer of Nafion. For in vitro demonstration of the platforms as a potential drug-screening system, A172 glioblastoma cells were cultured and transferred into the 24-well arrays. Simultaneous and direct monitoring of NO and O(2)(-) production as a response to chemicals of biomedical relevance was carried out. The results obtained demonstrated that it would be possible to envisage a drug screening platform for compounds designed to be inhibitors of nitric oxide synthase or to have an inhibitory effect on superoxide free radical production. By suitable modification of the electrodes employed it would also be possible to extend the platform to measure alternative species.

Biosensing Techniques↗

PubMed2026

Scalable medium-density genotyping platforms for cultivar identification, pedigree authentication, marker-assisted and genomic selection, and other applications in strawberry.

A broad spectrum of high-density genotyping approaches, including single-nucleotide polymorphism (SNP) arrays, genotyping-by-sequencing, and whole-genome reduced-representation sequencing, have been shown to perform well in strawberry (Fragaria × ananassa), despite the inherent complexity of the octoploid genome. While these approaches are effective, their routine deployment in breeding programs can be constrained by cost, computational requirements, and workflow complexity. In parallel, many breeding programs continue to rely on locus-specific assays for marker-assisted selection, resulting in fragmented and inefficient genotyping strategies. Here, we describe medium-density amplicon-based genotyping platforms for strawberry designed to provide cost-effective, turnkey solutions that integrate markers used for marker-assisted selection with genome-wide markers suitable for genomic prediction in a single laboratory assay. These platforms were developed by targeting 1,650 or 4,811 target SNPs via amplicon sequencing, and are interoperable with existing high-density genotyping resources, including a widely used 50K SNP array, thereby facilitating data integration across platforms. We benchmarked their performance relative to the 50K SNP array across breeding-relevant applications, including identity and purity testing, pedigree authentication, marker-assisted selection, and genomic selection, and further evaluated the feasibility of genotype imputation to enhance genome-wide information content. Across analyses, the 1,650- and 4,811-amplicon platforms produced results comparable to higher-density platforms while substantially reducing genotyping cost and analytical overhead. This work demonstrates that targeted amplicon-based genotyping can support efficient, scalable, and integrated genome-informed breeding, enabling the routine application of both marker-assisted and genomic selection within strawberry breeding workflows. Open-source R workflows are provided to support streamlined analyses in breeding contexts.

Fragaria↗

PubMed2004

Neurotransmitter analog tethered to a silicon platform for neuro-BioMEMS applications.

The design of chemically well-defined, machinable surfaces containing neuroactive molecules offers potential for fundamental neuroscience and clinical neural engineering applications. Here we report the assembly and characterization of silicon platforms containing a tethered form of muscimol. Muscimol, an analog of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), is a potent agonist at postsynaptic GABA(A) and GABA(C) receptors. Surfaces were assembled using covalent avidin conjugation to silanized silicon followed by high-affinity avidin-biotin binding of a biotinylated derivative of muscimol (muscimol-biotin). Contact angle measurements, ellipsometry, and X-ray photoelectron spectroscopy (XPS) were conducted to characterize the wettability, thickness, and chemical composition of progressively deposited surface layers. The data demonstrate successful incorporation of a neurotransmitter analog as part of a layered, silicon-based structure possessing robust and specific biomolecular composition. These findings represent a step toward the design of platforms for applications involving control and modulation of neural signaling.

Avidin↗

PubMed2006

Polymeric nanolayers as actuators for ultrasensitive thermal bimorphs.

Polymeric nanolayers are introduced here as active, thermal-stress mediating structures facilitating extremely sensitive thermal detection based upon the thermomechanical response of a bimaterial polymer-silicon microcantilever. To maximize the bimaterial bending effect, the microcantilever bimorph is composed of stiff polysilicon, with a strongly adhered polymer deposited via plasma-enhanced chemical vapor deposition. The polymer layers with thickness ranging from 20 to 200 nm possess a rapid and pronounced response to temperature fluctuations due to intrinsic sensitive thermal behavior. We show that by taking advantage of the thermal stresses generated by the huge mismatch of material properties in the polymer-silicon bimorph, unprecedented thermal sensitivities can be achieved. In fact, the temperature resolution of our bimaterial microcantilevers approaches 0.2 mK with thermal sensitivity reaching 2 nm/mK; both parameters are more than an order of magnitude better than the current metal-ceramic design. This new hybrid platform overcomes the inherently limited sensitivity of current sensor designs and provides the basis to develop the ultimate uncooled IR microsensor with unsurpassable sensitivity.

Crystallization↗

PubMed1998

Octamer-primed cycle sequencing using dye-terminator chemistry.

Octamer Sequencing Technology, OST, is a method of DNA sequencing using single octamer oligonucleotides to prime cycle sequencing reactions. This sequencing strategy is faster than a traditional primer-walking strategy, since access to this optimized octamer library eliminates delays associated with designing and synthesizing gene specific primers. In this report, OST has been optimized for fluorescent, dye-terminator cycle sequencing reactions to facilitate parallel processing of samples. The successful adaptation of OST to an automated sequencing platform and the design of and access to an octamer library are critical steps towards developing an efficient 'closed-loop' DNA sequencing system.

Animals↗

PubMedDate not supplied

ClinfoTracker: a generalizable prompting tool for primary care.

BACKGROUND: ClinfoTracker is a prompt and reminder system designed as a platform for the study of the cognitive aspects of prompting in primary care. We examined the impact of ClinfoTracker in three practices and its potential for studying primary care clinicians' use of prompt and reminder systems. METHODS: We studied ClinfoTracker in three practices using an observational design. We measured performance rates of three services during the course of 5 years in one practice and prompt response rates in all three practices for 5 months after implementation. We performed qualitative cognitive task analyses of ClinfoTracker use. RESULTS: Five-year compliance rates increased for fecal occult blood testing (1996-2000, 22.5%, P = .0037; 1997-2000, 23.5%, P = .0024) and type 2 diabetes retinopathy testing (1997-2000, 15.7%, P = .0004; 1998-2000, 16.9%, P = .0001; 1999-2000, 12.4%, P = .0048). ClinfoTracker response rates from the three practices showed significant increases during 5 months (P < .0001). Significant differences seen between practice response rates indicate variable success in ClinfoTracker implementation. Cognitive task analyses performed at site 1 indicate differences in how ClinfoTracker prompts are incorporated into practice. CONCLUSIONS: Improvements in preventive and disease management services after implementation show the potential of ClinfoTracker. Differences in implementation between practice sites and observations of individual clinicians show the promise ClinfoTracker holds for studying clinician use of prompt and reminder systems.

Analysis of Variance↗

PubMed2004

Influences of sterilising techniques on polyethylene wear.

Over the last 10 years there has been increasing concern over wear of polyethylene and osteolytic potential in the knee. During this period there have been considerable developments in both the design, materials and sterilisation techniques used for polyethylene in the knee. This paper reviews wear performance of polyethylene sterilised by different techniques, under a range of kinematics conditions in a single knee joint simulator system. Reducations in polyethylene wear were found with both stabilised polyethylene and cross-linked polyethylene, and with rotating platform mobile bearing designs.

Biomechanical Phenomena↗

PubMed2006

Concave reflective SU-8 photoresist gratings for flat-field integrated spectrometers.

On-chip spectrometry will play a leading role in the development of micro-optofluidic systems for analytical chemistry. Integrated spectrometers fabricated using a polymer-on-silicon platform have been designed, fabricated, and characterized. Reflective grating designs have been implemented using a recursive algorithm to calculate the facet positions as described by McGreer [Appl. Opt. 35, 5904 (1996)]. It is shown that the free spectral range, the output focal plane geometry, and the linear dispersion can be selected with a high degree of control independently of the chosen grating order. The polymer-on-silicon platform facilitates integration with microfluidic circuits and cost-efficient batch fabrication.

Journal Article↗

PubMed1999

Santorio Sanctorius (1561-1636) - founding father of metabolic balance studies.

The intellectual renaissance of the closing decades of the sixteenth century provided the fertile ground in which the budding spirit of scientific inquiry emerged in the seventeenth century. Direct observation, soon augmented by instrumentation that allowed for quantification and, therefore, verification, became the revelatory medium for the progress of the sciences. In medicine, progress depended on the application of the exact sciences of chemistry, mathematics and physics to the study of function. One of the medical luminaries of this early scientific revolution was Santorio Sanctorius (1561- 1636), whose principal contributions were his studies on insensible perspiration and his instrumental inventions. To study insensible perspiration, he designed a movable platform attached to a steelyard scale that allowed for the quantification of changes in body weight of subjects who partook in their daily activities on the platform. After years of self-experimentation, he applied his device to the study of patients. Unfortunately, his records are lost. What survives is a summary of his observations in a series of aphorisms published under the title of Ars de statica medicina, in 1614; 3 years after he was appointed Ordinary Professor of Theoretical Medicine in Padua. To enhance the bedside evaluation of patients, he also designed instruments to quantify the pulse, temperature, and environmental humidity. For his pioneering and detailed balance studies, Sanctorius clearly deserves the title of founding father of metabolic balance studies.

Equipment and Supplies↗

PubMed2006

Rational design of Salmonella-based vaccination strategies.

A permanently growing body of information is becoming available about the quality of protective immune responses induced by mucosal immunization. Attenuated live bacterial vaccines can be administered orally and induce long-lasting protective immunity in humans without causing major side effects. An attenuated Salmonella enterica serovar Typhi strain is registered as live oral vaccine against typhoid fever and has been in use for more than two decades. Recombinant attenuated Salmonella strains are also an attractive means of delivering heterologous antigens to the immune system, thereby, stimulating strong mucosal and systemic immune responses and consequently provide an efficient platform technology to design novel vaccination strategies. This includes the choice of heterologous protective antigens and their expression under the control of appropriate promoters within the carrier strain. The availability of well-characterized attenuated mutants of Salmonella concomitantly supports fine tuning of immune response triggered against heterologous antigens. Exploring different mucosal sites as a potential route of immunization has to be taken into account as an additional important way to modulate immune responses according to clinical requirements. This article focuses on the rational design of strategies to modulate appropriate immunological effector functions on the basis of selection of (i) attenuating mutations of the Salmonella strains, (ii) specific expression systems for the heterologous antigens, and (iii) route of mucosal administration.

Animals↗

PubMed2005

Drug discovery in the kinase inhibitory field using the Nested Chemical Library technology.

Kinase inhibitors are at the forefront of modern drug research, where mostly three technologies are used for hit-and-lead finding: high throughput screening of random libraries, three-dimensional structure-based drug design based on X-ray data, and focused libraries around limited number of new cores. Our novel Nested Chemical Library (NCL) (Vichem Chemie Research Ltd., Budapest, Hungary) technology is based on a knowledge base approach, where focused libraries around selected cores are used to generate pharmacophore models. NCL was designed on the platform of a diverse kinase inhibitory library organized around 97 core structures. We have established a unique, proprietary kinase inhibitory chemistry around these core structures with small focused sublibraries around each core. All the compounds in our NCL library are stored in a big unified Structured Query Language database along with their measured and calculated physicochemical and ADME/toxicity (ADMET) properties, together with thousands of molecular descriptors calculated for each compound. Biochemical kinase inhibitory assays on selected, cloned kinase enzymes for a few hundred NCL compound sets can provide sufficient biological data for rational computerized design of new analogues, based on our pharmacophore model-generating 3DNET4W QSPAR (quantitative structure-property/activity relationships) approach. Using this pharmacophore modeling approach and the ADMET filters, we can preselect synthesizable compounds for hit-and-lead optimization. Starting from this point and integrating the information from QSPAR, high-quality leads can be generated within a small number of optimization cycles. Applying NCL technology we have developed lead compounds for several validated kinase targets.

Algorithms↗

PubMed2002

Structure-based design of a novel peptide inhibitor of HIV-1 integrase: a computer modeling approach.

The insertion of viral DNA into the host chromosome is an essential step in the replication of HIV-1, and is carried out by an enzyme, HIV-1 integrase (IN). Since the latter has no human cellular counterpart, it is an attractive target for antiviral drug design. Several IN inhibitors having activities in the micromolar range have been reported to date. However, no clinically useful inhibitors have yet been developed. Recently reported diketo acids represent a novel and selective class of IN inhibitors. These are the only class which appear to selectively target integrase and two of the inhibitors, L-708,906 and L-731,988, are the most potent inhibitors of preintegration complexes described to date. The X-ray crystal structure of the IN catalytic domain complexed with a diketo acid derivative inhibitor, 5CITEP, has recently been determined. Although the structure is of great value as a platform for drug design, experimental data suggest that crystal packing effects influence the observed inhibitor position. This has been confirmed by computational docking studies using the latest version (3.0) of the AutoDock program, which has been shown to give results largely consistent with available experimental data. Using AutoDock 3.0 and SYBYL6.6 we have modeled the complexes of IN with the diketo acid inhibitors so as to identify the enzyme binding site. In the quest for novel, potent and selective small molecule inhibitors, we present here a new approach to peptide inhibitor design using a, b- unsaturated (dehydro) residues, which confer a unique conformation on a peptide sequence. Based on the above models, we selected a tetrapeptide sequence containing a dehydro-Phe residue, which was found to have an open conformation as ascertained from its X-ray crystal structure. Docking results on this peptide led us to propose a modification at the C-terminal end. The modified peptide was found to dock in a similar position as the diketo acid inhibitors and was predicted to have a comparable potency.

Acetoacetates↗