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Results for “platform design”

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At least 127 records · Page 7Linked to original sources

PubMed2006

Design and biological evaluation of novel tubulin inhibitors as antimitotic agents using a pharmacophore binding model with tubulin.

Although the structure has been elucidated for the binding of colchicine and podophyllotoxin as potent destabilizer for microtubule formation, very little is known about MDL-27048, a competitive inhibitor for colchicine and podophyllotoxin. The structural basis for the interaction of antimitotic agents with tubulin was investigated by molecular modeling, and we propose binding models for MDL-27048 against tubulin. The proposed model was not only consistent with previous competition experiment data between colchicine and MDL-27048, but further suggested an additional binding cavity on tubulin. Based on this finding from the proposed MDL-tubulin complex, we performed molecular design studies to identify new antimitotic agents. These new chalcone derivatives exerted growth inhibitory effects on all four human hepatoma and one renal epithelial cell lines tested and induced strong cell cycle arrest at G2/M phase. Furthermore, these compounds exhibited a strong inhibitory effect on tubulin polymerization in vitro. Therefore, we suggest that the validated MDL-27048 model would serve as a potent platform for designing new molecular entities for anticancer agents targeted to microtubules.

Cell Line↗

PubMed2000

Computerized assessment of voluntary control in the shift of the center of pressure: a pilot study.

The aim of the study was to test a new stabilometric platform (BioGP) designed to provide visual feedback to patients with balance disorders performing sustained voluntary shifts of their center of pressure (COP). Twenty-five outpatients with mild to moderate impairments of balance due to multiple sclerosis (MS) and 23 healthy subjects volunteered for the study. Patients' control of balance in static conditions was first rated on the Ataxia Battery and the Motricity Index; all subjects were then asked to stand on the platform in front of a large screen and try to move a visual target representing the momentary position of their COP along two vertical paths and one horizontal paths by appropriate movements of their hips and ankles along the lateral and antero-posterior planes. To assess the validity of BioGP, clinical scores of static balance were correlated with measures of speed and accuracy on the platform tasks. To assess the sensitivity of the equipment to poor balance control, patients' measures were compared with those of healthy subjects. Pearson's correlation coefficients between the Ataxia Battery scores and BioGP data ranged between -0.4 and - 0.82. As a group, patients performed statistically worse than controls on most BioGP measures. The graphic output of BioGP also contributed to define the dynamic relations between momentary COP position and balance control. These preliminary findings suggest a possible use of the system as both an evaluation and rehabilitation instrument.

Adult↗

PubMed2006

Mobile-bearing total knee arthroplasty: design factors in minimizing wear.

Premature polyethylene wear is a major cause of total knee arthroplasty (TKA) failure. It has been attributed to numerous factors including poor surgical technique, reduced polyethylene thickness, poor locking mechanisms of modular fixed bearing tibial components, gamma irradiation sterilization techniques in the presence of oxygen, and low conformity implant designs. The incidence of implantation of TKA into younger patients who have increased activity requirements and longevity expectations is increasing. This requires continued analysis of design features lessening polyethylene wear. The purpose of this manuscript is to review clinical and basic scientific studies of factors influencing polyethylene wear, focusing on the potential benefits of mobile bearing TKA which potentially reduce long-term polyethylene wear by providing increased implant conformity and reduced polyethylene contact stresses. In vivo kinematic studies have shown self-alignment of the polyethylene bearing with the femoral component typically occurs in rotating platform TKA designs which should hypothetically lessen polyethylene surface stresses, minimize stabilizing post impingement, and increase the potential for enhanced polyethylene longevity.

Humans↗

PubMed2006

A new user-friendly software platform for systematic classification of skin lesions to aid in their diagnosis and prognosis.

BACKGROUND AND AIMS: The field of much less invasive nonablative aesthetic surgery continues to grow, but consistent and truly objective evaluation of the sometimes comparatively small improvements in the treated skin remains a problem for both clinicians and patients. In this work, we present the development of a generic, modular and expandable platform to allow user-friendly image manipulation, sampling extraction and computer-assisted evaluation of tissue features in the dermatological/aesthetic field of clinical medicine. MATERIALS AND METHODS: The unique characteristic of the platform is the modular extension of the algorithm gallery by the use of extended value added services, which enables the easy incorporation of new image processing procedures to customise the gallery for specific concerns. A novel algorithm to evaluate skin wrinkles is also presented as a demonstration of this integration process. The software platform is designed to evaluate image-tissue indices and to identify individual or combined descriptors which will more accurately represent differences in skin quality. It is based on a set of indices correlating clinical expert and computer classifications, which build up a constantly expanding tissue catalogue. By means of this catalogue, the different tissue qualities of photographic samples can be assessed according to the different positions of the samples in the catalogue. CONCLUSIONS: This new platform can be used to generate sensitive and objective comparative measurement not only for diagnostic reports on the pre-treatment condition of samples but also for demonstrating the improvement and efficacy of the prescribed treatment to both the clinician and colleagues and the patient, thereby helping to increase the patient satisfaction index.

Algorithms↗

PubMed2026

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n = 65) or routine nursing only (n = 65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6 months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6 months ranged from small for resilience (D = 0.28) and avoidance coping (D = 0.26) to moderate for confrontation coping (D = 0.60) and resignation coping reduction (D = -0.51), and large for attributional style (D = 0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans↗

PubMed2006

High-throughput isolation of ultra-pure plasmid DNA by a robotic system.

BACKGROUND: With the availability of complete genomes, a systematic inventory of cellular processes becomes achievable. This requires assessing the function of all individual genes. Transfection of plasmid DNA into cell culture cells is an essential technique for this aim as it allows functional overexpression or downregulation of genes. While many robotic systems isolate plasmids for sequencing purposes, for more demanding applications such as transfections there is a shortage of robots for the high-throughput isolation of plasmid DNA. RESULTS: Here we describe a custom-made, automated device, which uses a special protocol to isolate plasmid DNAs with a purity sufficient for efficient transfections into mammalian cells. Approximately 1,600 ultra pure plasmids can be isolated in a 96-well plate format within 12 hours. As a unique feature the robot comprises the integration of a centrifuge instead of expensive columns, the use of a custom-made pipetting head with a movable gripper, especially designed shaking platforms and an acetone wash facility. CONCLUSION: Using this robot we demonstrate how centrifugation steps with multiple precipitations, most notably through a precipitation step of SDS in isopropanol, lead to high purity plasmid DNA and make possible high-throughput transfections into mammalian cells for functional gene annotations.

Chemical Fractionation↗

PubMed1991

One-eye and locomotor compensation in guinea pigs.

This study was carried out to examine the effect of blindfolding one eye on locomotor compensation after unilateral labyrinthectomy in guinea pigs. A platform runway, designed to examine the locomotion of this species of animals, was used. Eighteen Hartley-strain albino guinea pigs were used. These animals were divided into three groups, with seven in the control group, six whose right eye had been surgically closed in another group, and five whose left eye had been surgically closed in yet another group. After 7 to 11 days of training, a chemical labyrinthectomy by chloroform injection into the middle ear was performed under light ether anesthesia. Animals were checked for locomotion daily by the aforementioned platform method for about a week until regaining preprocedure levels. The locomotor compensation, depicted through the decrement of the deviation count and running time, was observed. Results have shown that the animal's locomotor compensation retarded significantly in the one-eye groups compared to the control group. In addition, those animals whose one eye, ipsilateral to the labyrinthectomy side, was closed required significantly longer time to resume the preprocedure running performance level than the animals whose one eye, contralateral to the lesion side, was closed. Thus, during locomotor compensation, the visual input obtained by animals with one eye ipsilateral to the labyrinthectomy side may be important compared to the visual input of the animals with the contralateral eye.

Animals↗

PubMed2026

Generation of a STRAIGHT-IN Dual AAVS1 hiPSC line with orthogonal landing pads for versatile DNA payload integration.

The STRAIGHT-IN platform is designed for facile genomic integration of DNA payloads into human induced pluripotent stem cells (hiPSCs) that contain a pre-inserted landing pad (LP). Here, we expanded the versatility of STRAIGHT-IN by introducing an additional, orthogonal LP into the unmodified allele of the safe harbor locus AAVS1. Specifically, we targeted the hiPSC line LUMC0099iCTRL04_AAVS1-bxb-v2 (hPSCreg LUMCi004-A-1), which already carried one LP. The resulting STRAIGHT-IN AAVS1 Dual line can integrate two independent DNA payloads in parallel, expanding the applicability of the platform for complex genomic engineering applications.

Humans↗

PubMed2006

Tissue engineering using human embryonic stem cells.

The possibility of using stem cells for tissue engineering has greatly encouraged scientists to design new platforms in the field of regenerative and reconstructive medicine. Stem cells have the ability to rejuvenate and repair damaged tissues and can be derived from both embryonic and adult sources. Among cell types suggested as a cell source for tissue engineering (TE), human embryonic stem cells (hESCs) are one of the most promising candidates. Isolated from the inner cell mass of preimplantation stage blastocysts, they possess the ability to differentiate into practically all adult cell types. In addition, their unlimited self-renewal capacity enables the generation of sufficient amount of cells for cell-based TE applications. Yet, several important challenges are to be addressed, such as the isolation of the desired cell type and gaining control over its differentiation and proliferation. Ultimately, combing scaffolding and bioactive stimuli, newly designed bioengineered constructs, could be assembled and applied to various clinical applications. Here we define the culture conditions for the derivation of connective tissue lineage progenitors, design strategies, and highlight the special considerations when using hESCs for TE applications.

Cell Culture Techniques↗

PubMed2004

MHC class II isotype- and allele-specific attenuation of experimental autoimmune encephalomyelitis.

Most autoimmune diseases are associated with certain MHC class II haplotypes. Autoantigen-based specific immune therapy can lead either to beneficial or, in the context of inflammatory conditions, detrimental outcomes. Therefore, we designed a platform of peptides by combinatorial chemistry selected in a nonbiased Ag-independent approach for strong binding to the rat MHC class II isotype RT1.D(n) allelic product of the RT1(n) haplotype that is presenting autoantigen in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in LEW.1N rats. Peptide p17 (Ac-FWFLDNAPL-NH(2)) was capable of suppressing the induction of and also ameliorated established experimental autoimmune encephalomyelitis. MHC class II isotype and allele specificity of the therapeutic principle were demonstrated in myelin basic protein-induced experimental autoimmune encephalomyelitis in LEW rats bearing the RT1(l) haplotype. A general immunosuppressive effect of the treatment was excluded by allogeneic heart transplantation studies. In vitro studies demonstrated the blocking effect of p17 on autoantigenic T cell responses. We thus demonstrate a rational design of strong MHC class II-binding peptides with absolute isotype and allele specificity able to compete for autoantigenic sequences presented on disease-associated MHC class II molecules.

Alleles↗

PubMed2026

CanVar-UK: A collaborative platform for germline interpretation in cancer susceptibility genes.

Germline variants in cancer susceptibility genes (CSGs) are typically inherited rather than arising de novo. Hence, wide cascade testing of families across geographies is common, meaning consistency in variant classification is particularly critical. Variant interpretation requires collation of variant-level data from diverse sources, as well as assembly of comprehensive clinical data, often necessitating sharing of information between genomic testing centers. Here, we describe CanVar-UK, a freely accessible web platform bespoke designed to support interpretation of germline CSG variants. CanVar-UK contains variant-level data for over 1.1 million single-nucleotide variants (SNVs), comprising all possible coding SNVs in 116 established CSGs. The data sources with which variants are annotated include in silico scores from 11 clinically relevant tools, population allele frequencies from gnomAD v4.1, case counts from multiple cohorts, including National Health Service (NHS) clinical laboratory testing, variant-level readouts from 47 selected functional and splicing datasets across 19 CSGs, genetic epidemiology studies, and live linkage to existing consensus classifications in the ClinVar database. The diagnostic discussion forum is only available to registered diagnostic scientist users. Through this, a variant-tagged email message can be dispatched in real time across the diagnostic forum community of >1,500 users, with all exchanges and classifications captured and stored in the platform. Already widely used by NHS diagnostic clinical scientists in the UK, CanVar-UK has a rapidly growing international diagnostic user base (>800 UK and >600 non-UK registered users). Survey of the NHS diagnostic user community illustrates the wide-ranging utility of CanVar-UK within their clinical workflows for interpretation of germline CSG variants.

Journal Article↗

PubMed2006

Mis-translation of a computationally designed protein yields an exceptionally stable homodimer: implications for protein engineering and evolution.

We recently used computational protein design to create an extremely stable, globular protein, Top7, with a sequence and fold not observed previously in nature. Since Top7 was created in the absence of genetic selection, it provides a rare opportunity to investigate aspects of the cellular protein production and surveillance machinery that are subject to natural selection. Here we show that a portion of the Top7 protein corresponding to the final 49 C-terminal residues is efficiently mis-translated and accumulates at high levels in Escherichia coli. We used circular dichroism, size-exclusion chromatography, small-angle X-ray scattering, analytical ultra-centrifugation, and NMR spectroscopy to show that the resulting C-terminal fragment (CFr) protein adopts a compact, extremely stable, homo-dimeric structure. Based on the solution structure, we engineered an even more stable variant of CFr by disulfide-induced covalent circularisation that should be an excellent platform for design of novel functions. The accumulation of high levels of CFr exposes the high error rate of the protein translation machinery. The rarity of correspondingly stable fragments in natural proteins coupled with the observation that high quality ribosome binding sites are found to occur within E. coli protein-coding regions significantly less often than expected by random chance implies a stringent evolutionary pressure against protein sub-fragments that can independently fold into stable structures. The symmetric self-association between two identical mis-translated CFr sub-domains to generate an extremely stable structure parallels a mechanism for natural protein-fold evolution by modular recombination of protein sub-structures.

Amino Acid Sequence↗

PubMed2004

Improved method for fluorescence cytometric immunohematology testing.

BACKGROUND: A method for accurate immunohematology testing by fluorescence cytometry (FC) was previously described. Nevertheless, the use of vacuum filtration to wash RBCs and a standard-flow cytometer for data acquisition hindered efforts to incorporate this method into an automated platform. STUDY DESIGN AND METHODS: A modified procedure was developed that used low-speed centrifugation of 96-well filter plates for RBC staining. Small-footprint benchtop capillary cytometers (PCA and PCA-96, Guava Technologies, Inc.) were used for data acquisition. Authentic clinical samples from hospitalized patients were tested for ABO group and the presence of D antigen (n = 749) as well as for the presence of RBC alloantibodies (n = 428). Challenging samples with mixed-field reactions and weak antibodies were included. Results were compared to those obtained by column agglutination technology (CAT), and discrepancies were resolved by standard tube methods. Detailed investigations of FC sensitivity and reproducibility were also performed. RESULTS: The modified FC method with the PCA determined the correct ABO group and D type for 98.7 percent of 520 samples, compared to 98.8 percent for CAT (p > 0.05). No-type-determined (NTD) rates were 1.2 percent for both methods. In testing for unexpected alloantibodies, FC determined the correct result for 98.6 percent of 215 samples, compared to 96.3 percent for CAT (p > 0.05). When samples were automatically acquired in the 96-well plate format with the PCA-96, 98.7 percent of 229 samples had correct ABO group and D type determined by FC, compared to 97.4 percent for CAT (p > 0.05). NTD rates were 0.9 and 2.6 percent, respectively. Antibody screens were accurate for 99.1 percent of 213 samples with the PCA-96, compared to 99.5 percent for CAT (p > 0.05). Further investigations demonstrated that FC with the PCA-96 was better than CAT at detecting weak anti-A (p < 0.0001) and alloantibodies. CONCLUSIONS: An improved method for FC immunohematology testing has been described. This assay was comparable in accuracy to standard CAT techniques, but had better sensitivity for detecting weak antibodies and was superior in detecting mixed-field reactions (p < 0.005). The FC method demonstrated excellent reproducibility. The compatibility of this assay with the PCA-96 capillary cytometer with plate-handling capabilities should simplify development of a completely automated platform.

Autoantibodies↗

PubMed2003

Through-space delocalized water-soluble paracyclophane bichromophores: new fluorescent optical reporters.

Conjugated polymers and oligomers can serve as highly responsive fluorescent reporters for biosensor applications. However, their optical properties in aqueous media are highly dependent upon environmental conditions. The structure of the paracyclophane framework provides a platform for designing optical reporters that show little sensitivity to surfactants, and thus is well-suited for fluorescent assays. The permanent intramolecular delocalization through the paracyclophane core dominates intermolecular perturbations in spontaneously formed aggregates.

Journal Article↗

PubMed2006

o-nitrobenzyl photolabile protecting groups with red-shifted absorption: syntheses and uncaging cross-sections for one- and two-photon excitation.

We evaluated the o-nitrobenzyl platform for designing photolabile protecting groups with red-shifted absorption that could be photolyzed upon one- and two-photon excitation. Several synthetic pathways to build different conjugated o-nitrobenzyl backbones, as well as to vary the benzylic position, are reported. Relative to the reference 4,5-dimethoxy-2-nitrobenzyl group, several o-nitrobenzyl derivatives exhibit a large and red-shifted one-photon absorption within the near-UV range. Uncaging after one-photon excitation was studied by measuring UV-visible absorption and steady-state fluorescence emission on model caged ethers and esters. In the whole series investigated, the caged substrates were released cleanly upon photolysis. Quantum yields of uncaging after one-photon absorption lie within the 0.1-1 % range. We observed that these drop as the maximum wavelength absorption of the o-nitrobenzyl protecting group is increased. A new method based on fluorescence correlation spectroscopy (FCS) after two-photon excitation was used to measure the action uncaging cross section for two-photon excitation. The series of o-nitrobenzyl caged fluorescent coumarins investigated exhibit values within the 0.1-0.01 Goeppert-Mayer (GM) range. Such results are in line with the low quantum yields of uncaging associated with cross-sections of 1-50 GM for two-photon absorption. Although the cross-sections for one- and two-photon absorption of o-nitrobenzyl photolabile protecting groups can be readily improved, we emphasize the difficulty in enlarging the corresponding action uncaging cross-sections in view of the observed trend of their quantum yield of uncaging.

Journal Article↗

PubMed1977

Wafer embedding: specimen selction in electron microscopic cytochemistry with osmiophilic polymers.

A new wafer embedding procedure is described that permits light microscopic screening of embedded tissue prior to ultrathin sectioning. It is particularly valuable when used on specimens obtained with an automatic sectioner and treated cytochemically to obtain visible intermediate or visible and electron opaque final reaction products. Aldehyde-fixed tissues are cut into sections with an automatic sectioner, incubated cytochemically osmication if required, then embedded in epoxy resin between fluorocarbon coverglasses which are supported by a platform specially designed for this purpose. The resultant wafter, less than 0.2 mm thick, is examined by light microscopy for optimal areas of cytochemical reaction and desirable structural features. Such areas are cut out and glued to blank blocks with fast curing cyanoacrylate cement for subsequent ultrathin sectioning. The usefulness of this technique is demonstrated by the location of: (1) esterase-positive lysosomes in kidney and trigeminal ganglia; (2) palatal sensory endings stained for acetylcholinesterase; and (3) phagosomes arising from the resorption of horseradish peroxidase tracer by the cuboidal parietal epithelial cells of Bowman's capsule in the male mouse.

Acetylcholinesterase↗

PubMed2006

Integration of microcolumns and microfluidic fractionators on multitasking centrifugal microfluidic platforms for the analysis of biomolecules.

This work demonstrates the development of microfluidic compact discs (CDs) for protein purification and fractionation integrating a series of microfluidic features, such as microreservoirs, microchannels, and microfluidic fractionators. The CDs were fabricated with polydimethylsiloxane (PDMS), and each device contained multiple identical microfluidic patterns. Each pattern employed a microfluidic fractionation feature with operation that was based on the redirection of fluid into an isolation chamber as a result of an overflow. This feature offers the advantage of automated operation without the need for any external manipulation, which is independent of the size and the charge of the fractionated molecules. The performance of the microfluidic fractionator was evaluated by its integration into a protein purification microfluidic architecture. The microfluidic architecture employed a microchamber that accommodated a monolithic microcolumn, the fractionator, and an isolation chamber, which was also utilized for the optical detection of the purified protein. The monolithic microcolumn was polymerized "in situ" on the CD from a monolith precursor solution by microwave-initiated polymerization. This technique enabled the fast, efficient, and simultaneous polymerization of monoliths on disposable CD microfluidic platforms. The design of the CD employed allows the integration of various processes on a single microfluidic device, including protein purification, fractionation, isolation, and detection.

Microfluidic Analytical Techniques↗

PubMed1976

A method of transferring mandibular-movement data to computer storage.

A method was briefly described which photographed engraved blocks of mandibular-movement recordings and transferred the information into computer memory. A photographic platform was designed to allow uniform photographing of the engraved blocks. The photographed information was then projected onto graph paper where it was traced. The traced information, with the centric point labeled, was transferred into computer memory via a Computek 531 tablet. An RMS (root-mean-squared) deviation test was conducted to estimate the reliability of this technique. The maximum deviation (0.363 mm.) was found for z coordinate of the left-side recording. Labeling the centric point in computer memory is very important. This allows careful and detailed study of movements in the area where clinical evaluation is of utmost importance to the dentist. As more data are collected and evaluated, questions related to occlusion, such as tooth stability, effect on periodontal health, relationship to orthodontic success, and the like, may be clarified.

Computers↗