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Results for “Functional verification”

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At least 307 records · Page 17Linked to original sources
PubMed2005

Determination of the modulation transfer function of digitally reconstructed radiographs in radiotherapy treatment planning using a point phantom.

Digitally reconstructed radiographs (DRRs) have become an important tool in radiotherapy treatment planning and treatment verification but their use can be limited by poor image quality. A point phantom comprised of a 1 mm diameter tungsten carbide ball bearing in a wax block has been manufactured as a means of determining a quantitative measure of DRR spatial resolution by calculating the modulation transfer function (MTF) of the image. This method is an alternative to the more often used bar pattern method. The effect of varying CT slice thickness upon DRR spatial resolution has been assessed and a power law relationship between the two variables has been established.

Equipment Design↗
PubMed1990

Good clinical practice.

Good Clinical Practice (GCP) is a quality assurance system dealing with all stages of clinical trials which is progressively being adopted by European countries. European GCP guidelines are in preparation and will be issued soon. However, implementation of the guidelines poses major and costly problems. The training of investigators, the proper functioning of research ethics committees, the practice of obtaining written informed consent, source data verification, and quality control with internal audit and official inspections are among the most difficult issues. The obvious benefits of GCP are the improved quality of clinical trials and of data generated by such trials, as well as mutual recognition of studies conducted abroad.

Anti-Infective Agents↗
PubMed2004

Development of candidate introgression lines using an exotic barley accession ( Hordeum vulgare ssp. spontaneum) as donor.

In the present paper, we report on the selection of two sets of candidate introgression lines (pre-ILs) in spring barley. Two BC2DH populations, S42 and T42, were generated by introgressing an accession of Hordeum vulgare ssp. spontaneum (ISR42-8, from Israel) into two different spring barley cultivars, Scarlett (S) and Thuringia (T). From these BC2DH populations two sets with 49 (S42) and 43 (T42) pre-ILs were selected, and their genomic architecture as revealed by SSR marker analysis was characterised. The selected pre-ILs cover at least 98.1% (S42) and 93.0% (T42) of the exotic genome in overlapping introgressions and contain on average 2 (S42) and 1.5 (T42) additional non-target introgressions. In order to illustrate a potential application and validation of these pre-ILs, the phenotypic effect of the exotic introgression at the locus of the major photoperiod response gene Ppd-H1 was analysed. Pre-ILs carrying the introgression at the Ppd-H1 locus flowered significantly earlier than the elite parents, and the introgression maintained its effect across the two genetic backgrounds and across four tested environments. The selected pre-ILs represent a first promising step towards the assessment and utilization of genetic variation present in exotic barley. They may promote the breeding progress, serve for the verification of QTL effects and provide a valuable resource for the unravelling of gene function, e.g. by expression profiling or map-based cloning.

Breeding↗
PubMed1991

Optimal coordination and control of posture and locomotion.

This paper presents a theoretical model of stability and coordination of posture and locomotion, together with algorithms for continuous-time quadratic optimization of motion control. Explicit solutions to the Hamilton-Jacobi equation for optimal control of rigid-body motion are obtained by solving an algebraic matrix equation. The stability is investigated with Lyapunov function theory, and it is shown that global asymptotic stability holds. It is also shown how optimal control and adaptive control may act in concert in the case of unknown or uncertain system parameters. The solution describes motion strategies of minimum effort and variance. The proposed optimal control is formulated to be suitable as a posture and stance model for experimental validation and verification. The combination of adaptive and optimal control makes this algorithm a candidate for coordination and control of functional neuromuscular stimulation as well as of prostheses.

Algorithms↗
PubMed2006

Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells.

The pulsatile nature of blood pressure and flow creates hemodynamic stimuli in the forms of cyclic stretch and shear stress, which exert continuous influences on the constituents of the blood vessel wall. Vascular smooth muscle cells (VSMCs) use multiple sensing mechanisms to detect the mechanical stimulus resulting from pulsatile stretch and transduce it into intracellular signals that lead to modulations of gene expression and cellular functions, e.g., proliferation, apoptosis, migration, and remodeling. The cytoskeleton provides a structural framework for the VSMC to transmit mechanical forces between its luminal, abluminal, and junctional surfaces, as well as its interior, including the focal adhesion sites, the cytoplasm, and the nucleus. VSMCs also respond differently to the surrounding structural environment, e.g., two-dimensional versus three-dimensional matrix. In vitro studies have been conducted on cultured VSMCs on deformable substrates to elucidate the molecular mechanisms by which the cells convert mechanical inputs into biochemical events, eventually leading to functional responses. The knowledge gained from research on mechanotransduction in vitro, in conjunction with verifications under in vivo conditions, will advance our understanding of the physiological and pathological processes involved in vascular remodeling and adaptation in health and disease.

Animals↗
PubMed2024

Systematic Proteome Profiling of Maternal Plasma for Development of Preeclampsia Biomarkers.

Preeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. Proteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver-operating characteristics curve (AUC). A total of 1307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Upregulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC >0.9 and p&#xa0;<&#xa0;0.001, for all) as validated by MRM and ELISA. Our data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women.

Humans↗
PubMedDate not supplied

Application of visual basic in high-throughput mass spectrometry-directed purification of combinatorial libraries.

We present an approach to customize the sample submission process for high-throughput purification (HTP) of combinatorial parallel libraries using preparative liquid chromatography electrospray ionization mass spectrometry. In this study, Visual Basic and Visual Basic for Applications programs were developed using Microsoft Visual Basic 6 and Microsoft Excel 2000, respectively. These programs are subsequently applied for the seamless electronic submission and handling of data for HTP. Functions were incorporated into these programs where medicinal chemists can perform on-line verification of the purification status and on-line retrieval of postpurification data. The application of these user friendly and cost effective programs in our HTP technology has greatly increased our work efficiency by reducing paper work and manual manipulation of data.

Combinatorial Chemistry Techniques↗
PubMedDate not supplied

Verification of the corrected Staggered Spondaic Word (SSW) score in adults with cochlear hearing loss.

Traditionally, tests of central auditory function have been limited when hearing loss is present. By design the Staggered Spondaic Word (SSW) test incorporates a correction procedure which attempts to account for the effects of peripheral distortion. Results obtained in the present study, based on 92 adult males with bilateral, cochlear hearing loss, showed no significant change in corrected SSW (C-SSW) scores in cases with a pure-tone average less than 50 dB. Uncorrected (R-SSW) scores were highly correlated with the word discrimination score, but this relationship was neutralized when the correction procedure was applied. An effect of hearing loss on the C-SSW was found to plateau after 50 dB Hl. The change in C-SSW may shift the performance category to a poorer range. Use of the C-SSW appears not to be compromised by cochlear hearing loss up to 50 dB. However, cross-validation of SSW scores with other audiometric results should be used particularly in cases of cochlear hearing loss greater than 40 to 50 dB.

Adult↗
PubMed2002

Portal dose image prediction for dosimetric treatment verification in radiotherapy. II. An algorithm for wedged beams.

A method is presented for calculation of a two-dimensional function, T(wedge)(x,y), describing the transmission of a wedged photon beam through a patient. This in an extension of the method that we have published for open (nonwedged) fields [Med. Phys. 25, 830-840 (1998)]. Transmission functions for open fields are being used in our clinic for prediction of portal dose images (PDI, i.e., a dose distribution behind the patient in a plane normal to the beam axis), which are compared with PDIs measured with an electronic portal imaging device (EPID). The calculations are based on the planning CT scan of the patient and on the irradiation geometry as determined in the treatment planning process. Input data for the developed algorithm for wedged beams are derived from (the already available) measured input data set for transmission prediction in open beams, which is extended with only a limited set of measurements in the wedged beam. The method has been tested for a PDI plane at 160 cm from the focus, in agreement with the applied focus-to-detector distance of our fluoroscopic EPIDs. For low and high energy photon beams (6 and 23 MV) good agreement (approximately 1%) has been found between calculated and measured transmissions for a slab and a thorax phantom.

Algorithms↗
PubMed1989

Increased production and/or secretion of pulmonary surfactant in rats by long term sulfur dioxide exposure.

Influence of long term SO2 exposure on the pulmonary surfactant in rats was studied by means of chemical analysis and microscopic verification. At a time after termination of the exposure period, the general symptom in rats was similar to that of bronchitis. The content of disaturated phosphatidylcholine, a main functional component of the pulmonary surfactant, significantly increased not only in broncho-alveolar lavage fluid but also in pulmonary microsomal fraction by long term SO2 exposure. Microscopic verification of alveolar type II cells from the bronchitic rats demonstrated the development of rough surface endoplasmic reticulums and an increase of the number of osmiophillic bodies. The results suggest that pulmonary surfactant production and/or secretion are activated in rats with bronchitis caused by long term SO2 exposure.

Animals↗
PubMed1989

[Endocrine consequences of infection by human immunodeficiency virus (HIV)].

The acquired immunodeficiency syndrome (SIDA) is a severe multivisceral affection that is sometimes composed of a clinical expression compatible with an endocrine insufficiency. The post-mortem verifications confirmed the high frequency of the suprarenal, pituitary and testicular lesions. The hormonal functional exploration confirmed the possibility of a decrease in the cortical suprarenal function that contrasts with a moderate hypercortisolemia and an hypogonadism without elevation of the gonadotrophins. The clinical expression of the deficits is unusual. Nevertheless a few cases of obvious suprarenal or antepituitary insufficiency bond to a secondary inflammatory necrosis, an infection by CMV, or a toxoplasmosis have been reported. More often, these hormonal alterations are moderate. There mechanisms are still imprecise. The non-specific response to the stress led by the disease doesn't give an explanation to the observed abnormalities. The described existence of antihormone antibodies in AIDS or the secretory potentialities of the activated lymphocytes might contribute to the physiopathology of the endocrine modifications outside of any infections or endocrine metastatical localisation.

Acquired Immunodeficiency Syndrome↗
PubMed2006

The cell surface leucine-rich repeat receptor for AtPep1, an endogenous peptide elicitor in Arabidopsis, is functional in transgenic tobacco cells.

AtPep1 is a 23-aa endogenous peptide elicitor from Arabidopsis leaves that signals the activation of components of the innate immune response against pathogens. Here, we report the isolation of an AtPep1 receptor from the surface of Arabidopsis suspension-cultured cells. An (125)I-labeled AtPep1 analog interacted with suspension-cultured Arabidopsis with a K(d) of 0.25 nM, and an (125)I-labeled azido-Cys-AtPep1 photoaffinity analog specifically labeled a membrane-associated protein of approximately 170 kDa. The labeled protein was purified to homogeneity, and its tryptic peptides were identified as gene At1g73080, which encodes a leucine-rich repeat receptor kinase, here called PEPR1. Verification of the binding protein as the receptor for AtPep1 was established by demonstrating the loss of function of microsomal membranes of two SALK insertional mutants and by a gain in function of the alkalinization response to AtPep1 by tobacco suspension-cultured cells expressing the At1g73080 transgene. Synthetic homologs of AtPep1, deduced from the C termini of six known paralogs of PROPEP1, were biologically active and were competitors of the interaction of an AtPep1 radiolabeled analog with the receptor. The data are consistent with a role for PEPR1 as the receptor for AtPep1 to amplify innate immunity in response to pathogen attacks.

Amino Acid Sequence↗
PubMed1987

Application of an equivalent circuit to signal-to-noise calculations in MRI.

Transfer functions determined from the component values of an equivalent circuit are used to calculate the relative signal-to-noise ratio of rf coils for magnetic resonance imaging. Experimental verification of the method is obtained by directly measuring signals from three solenoidal coils and by measuring the signal-to-noise ratio of these solenoids. The transfer functions separate the total noise voltage into contributions from the coil resistance and contributions from magnetic and electric field interactions with the sample. The use of this technique in understanding and improving coil design is discussed.

Magnetic Resonance Spectroscopy↗
PubMed2006

Computational estimation and experimental verification of off-target silencing during posttranscriptional gene silencing in plants.

Successful application of posttranscriptional gene silencing (PTGS) for gene function study in both plants and animals depends on high target specificity and silencing efficiency. By computational analysis with genome and/or transcriptome sequences of 25 plant species, we predicted that about 50% to 70% of gene transcripts in plants have potential off-targets when used for PTGS that could obscure experimental results. We have developed a publicly available Web-based computational tool called siRNA Scan to identify potential off-targets during PTGS. Some of the potential off-targets obtained from this tool were tested by measuring the amount of off-target transcripts using quantitative reverse transcription-PCR. Up to 50% of the predicted off-target genes tested in plants were actually silenced when tested experimentally. Our results suggest that a high risk of off-target gene silencing exists during PTGS in plants. Our siRNA Scan tool is useful to design better constructs for PTGS by minimizing off-target gene silencing in both plants and animals.

Agrobacterium tumefaciens↗
PubMed2025

Efficient and versatile rapeseed transformation for new breeding technologies.

Many gene functions are widely studied and understood in Arabidopsis; however, the lack of efficient transformation systems often limits the application and verification of this knowledge in crop plants. Brassica napus L., a member of the Brassicaceae family, is usually transformed by Agrobacterium-mediated hypocotyl transformation, but not all growth types are equally amenable to transformation. In particular, winter rapeseed, which requires vernalization to initiate flowering, is recalcitrant to in vitro regeneration and transformation. The analysis of gene functions in rapeseed is further complicated by the allotetraploid nature of its genome and the genome triplication within the Brassica genus, which has led to the presence of a large number of gene homologs for each Arabidopsis ortholog. We have established a transformation method that facilitates the regeneration of winter rapeseed by using the WUSCHEL gene from Beta vulgaris. This allowed us to efficiently transform a winter and spring rapeseed genotype in small-scale experiments. As proof of principle, we targeted BnCLV3 and BnSPL9/15 with CRISPR/Cas9 and showed that entire gene families are effectively edited using this transformation protocol. This allowed us to simultaneously study many redundantly acting homologous genes in rapeseed. We observed mutant phenotypes for BnCLV3 and BnSPL9/15 in primary transformants, indicating that biallelic knockouts were obtained for up to eight genes. This allowed an initial phenotypic characterization to be performed already a few months after starting the experiment.

Brassica napus↗
PubMed2000

Identification of gel-separated tumor marker proteins by mass spectrometry.

Two-dimensional gel electrophoresis with subsequent analysis by mass spectrometry was applied to study differences in protein expression between benign and malignant solid tumors from human beast, lung and ovary cells. Cells from freshly resected clinical material were lysed and the extracts were subjected to isoelectric focusing with immobilized pH gradients followed by second-dimensional separation on 10-13% sodium dodecyl sulfate (SDS)/polyacrylamide gels. Polypeptides were identified using matrix-assisted laser desorption/ionization and electrospray ionization mass spectrometry after in-gel protein digestion. Some of the upregulated polypeptides in malignant cells are of potential importance as markers of tumor proliferation. Twenty such proteins were identified, ten constituting novel identifications and ten sequence verifications of previously gel-matched proteins. The proteins identified span a wide range of functions, but several cases of protein truncation were found. Truncated forms of cytokeratins 6D and 8, and of cathepsin D were identified. Truncated froms of these over-expressed proteins support the presence of proteolytic processing steps in tumor material. The protein processing and the difference between protein and mRNA abundancies in tumors of different malignancy and origin suggest that studies at the protein level are important for an understanding of tumor phenotypes.

Biomarkers, Tumor↗
PubMed2000

Molecular cloning of a taxa-4(20),11(12)-dien-5alpha-ol-O-acetyl transferase cDNA from Taxus and functional expression in Escherichia coli.

The taxa-4(20),11(12)-dien-5alpha-ol-O-acetyl transferase which catalyzes the third step of Taxol biosynthesis has been isolated from methyl jasmonate-induced Taxus cells, and partially purified and characterized (K. Walker, R. E. B. Ketchum, M. Hezari, D. Gatfield, M. Golenowski, A. Barthol, and R. Croteau, Arch. Biochem. Biophys. 364, 273-279 1999). A revised purification method allowed internal amino acid microsequencing of the enzyme, from which primers were designed and employed to amplify a transacetylase gene-specific fragment. This radiolabeled, 900-bp amplicon was used as a hybridization probe to screen a cDNA library constructed from poly(A)(+) RNA isolated from induced Taxus cells, from which a full-length transacetylase sequence was obtained. Expression of this clone from pCWori(+) in Escherichia coli JM109 cells yielded the functional enzyme, as determined by radiochemical assay and combined capillary gas chromatographic-mass spectrometric verification of the acetylated product. The full-length DNA has an open-reading frame of 1317 nucleotides corresponding to a deduced amino acid sequence of 439 residues that exhibits high sequence identity to the proteolytic fragments of the native enzyme, which the recombinant transacetylase resembles in properties. Consistent with the size of the operationally soluble native enzyme, the DNA appears to encode a monomeric protein of molecular weight 49,079 that bears no N-terminal organellar targeting information. Sequence comparison of the taxadien-5alpha-ol-O-acetyl transferase with the few other known acyl transferases of plant origin indicates a significant degree of similarity between these enzymes (64-67%). The efficient conversion of taxadien-5alpha-yl acetate to further hydroxylated intermediates of the Taxol pathway confirms the significance of this acylation step and suggests this taxadienol transacetylase to be an important target for genetic manipulation to improve Taxol production.

Acetyltransferases↗
PubMed1992

Aldose reductase inhibitors and diabetic complications.

Aldose reductase inhibitors impede flux of glucose through the sorbitol pathway in diabetes mellitus. They therefore reduce the accumulation of the pathway metabolites, sorbitol and fructose, reduce the impact of the flux on the cofactors used by the pathway and reduce other derived phenomena, such as osmotic stress and myo-inositol depletion. As drugs, their targets are the chronic complications of diabetes--neuropathy, retinopathy, nephropathy and vasculopathy. In experimental models there is proof of activity against biochemical, functional and structural defects in all of the involved tissues, but we await full clinical verification of this potential.

Aldehyde Reductase↗