Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Functional verification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,063 records · Page 59Linked to original sources

An Assessment of Improvement in Reliability and Completeness of Mumbai Cancer Registry Data from 1964-1997.

The Mumbai Cancer Registry was established in 1964 with the aim of obtaining reliable morbidity and mortality data from precisely defined urban population. It was first and only such registry for merely two decades functioning in the country. Up to now more than 200,000 cancer cases are registered and with over 100,000 cancer deaths are recorded in data files. For studying improvements in the Mumbai Cancer Registry data, the data published in consecutive seven volumes (Vol.-II to Vol.-VIII) of "Cancer Incidence of Five Continents published by International Agency on Research on Cancer", Lyon, France have been used. For studying completeness of the data, the indicators 'Proportion of Deaths in Period'; 'Proportion of Death Certificates only' and stability of age incidence rates have been utilized. The indicators 'Proportion of cases registered on histological verification', 'The proportion of cases where age is not known', 'The flattening of age incidence curve' and 'Proportion of other and unspecified neoplasms can throw some light on the quality of data collected by the registry. There has been notable improvement in percentages of histological verification cases and substantial decrease in the proportion of death certificate alone cases in both the sexes over a period of time. Mortality Incidence ratio remained stable over a period of time in both the sexes. The proportion of cases where age is not known never exceeded 0.020% in either sex, for any site, for any period. The proportion of cases registered as other and unspecified sites, initially was around 8 to 9% then it has been dropped down to 5%. The crude incidence rates for all sites together are stable throughout the period of observation in both the sexes while age adjusted incidence rates show declining trend in both the sexes. There is no change in the pattern of age-specific incidence curves over a period of time in both the sexes. On examining various indices of reliability and completeness of Mumbai cancer registry data it can be concluded that, the data collected by this registry is quiet complete and reliable. While applying various checks for validity for a period from 1964-66 to 1993-97, it indicates that there is quiet improvement in almost all indices over a period of time in Mumbai cancer registry data.

Journal Article↗

The pressure-flow relation for plasma in whole organ skeletal muscle and its experimental verification.

The whole-organ pressure-flow relation in resting rat skeletal muscle is examined for the flow of plasma. Due to the small size of the blood vessels in this organ, inertia and convective forces in the blood are negligible and viscous forces dominate. Direct measurements in the past have shown that skeletal muscle blood vessels are distensible. Theoretical formulations based on these measurements lead to a third order polynomial model for the pressure-flow relation. The purpose of the current study is to examine this relation experimentally in an isolated muscle organ. A high precision feedback controlled pump is used to perfuse artificial plasma into the vasodilated rat gracilis muscle. The results indicate that the pressure-flow curve in this tissue is nonlinear in the low flow region and almost linear at physiological flow rates, following closely the third order polynomial function. Vessel fixation with glutaraldehyde causes the curves to become linear at all pressures, indicating that vessel distention is the primary mechanism causing the nonlinearity. Furthermore, the resistance of the post-fixed tissue is determined by the pressure at which the fixative is perfused. At fixation pressures below 10 mmHg, the resistance is three times higher than in vessels fixed at normal physiological pressures. Dextran (229,000 Dalton) is used to obtain Newtonian perfusates at different viscosities. The pressure-flow relation is found to be linearly dependent on viscosity for all flow rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Functional aberrant expression of CCR2 receptor on chronically activated NK cells in patients with TAP-2 deficiency.

Chemokines play a pivotal role in homeostatic and inflammatory migration of naive and activated natural killer (NK) subsets. Recent studies have shown that aberrant chemokine receptor expression on certain immune cells underlies the pathogenesis of clinical conditions in which recruitment of such cells is altered. Progressive accumulation of activated NK cells, subsequently resulting in the formation of chronic granulomatous lesions in the respiratory tract and the skin, has been described in a number of patients with transporter associated with antigen processing 2 (TAP-2) deficiency in the later stages of disease. Therefore, the goal of the present study was to elucidate whether the dysregulation of chemoattracting receptor expression on NK cells could explain abnormal navigation of these cells in TAP-2 deficiency. High-throughput proteomic comparison, followed by verification with flow cytometry, revealed that chronically activated NK cells derived from 3 newly identified patients with TAP-2 deficiency consistently expressed aberrant levels of CC chemokine receptor 2 (CCR2) chemokine receptor in vitro and in vivo. This expression pattern translated into specific responsiveness of chronically activated NK cells derived from patients with TAP-2 deficiency to multiple ligands of CCR2. Moreover, the in vivo elevated levels of interleukin-2 (IL-2) and monocyte chemoattractant protein-1 (MCP-1) detected in serum and bronchoalveolar lavage samples derived from these patients highlight the potential involvement of the CCR2 pathway in aberrant NK-cell retention at chronic inflammatory sites.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A new method for stoichiometric analysis of proteins in complex mixture--reevaluation of the stoichiometry of E. coli ribosomal proteins.

A novel way is presented for determination of the stoichiometry of ribosomal proteins in the ribosome. The 70S E. coli r-proteins, completely separated on a two-dimensional gel system, were used throughout our experiments. The method is based on our previous observation that the amount of Coomassie R bound to a protein molecule is directly proportional to the number of positive charges on that protein. By plotting the amount of bound Coomassie as a function of the number of positive charges of each r-protein, and relating the experimental amount of the dye bound to each r-protein to the value obtained from the linear regression line based on all (a total of some 50 proteins), one can obtain the molar concentration of every protein in the ribosome. A parallel experiment can be carried out, which relates the radioactivity contributed by 3H-labeled amino acid in each r-protein to its amino acid content in that molecule. The two sets of data, which are completely independent of each other, are well correlated. Further verification of the validity of our procedure is provided by the fact that we found the known proportions of four copies of L7/L12 and one copy of S6 per ribosome. The rationale behind the present study was our finding that recalculation of Hardy's data (Hardy, S.J.S. (1975) Mol. Gen. Genet. 140, 253-274), with the accurate molecular weight value of the r-proteins provided by Giri et al. (Adv. Protein Chem. (1984) 36, 1-78), raises some doubt with regard to his experimental results, although we agree with his final conclusion that E. coli ribosome is homogeneous with respect to its proteins.

Bacterial Proteins↗

Performance characterization of megavoltage computed tomography imaging on a helical tomotherapy unit.

Helical tomotherapy is an innovative means of delivering IGRT and IMRT using a device that combines features of a linear accelerator and a helical computed tomography (CT) scanner. The HI-ART II can generate CT images from the same megavoltage x-ray beam it uses for treatment. These megavoltage CT (MVCT) images offer verification of the patient position prior to and potentially during radiation therapy. Since the unit uses the actual treatment beam as the x-ray source for image acquisition, no surrogate telemetry systems are required to register image space to treatment space. The disadvantage to using the treatment beam for imaging, however, is that the physics of radiation interactions in the megavoltage energy range may force compromises between the dose delivered and the image quality in comparison to diagnostic CT scanners. The performance of the system is therefore characterized in terms of objective measures of noise, uniformity, contrast, and spatial resolution as a function of the dose delivered by the MVCT beam. The uniformity and spatial resolutions of MVCT images generated by the HI-ART II are comparable to that of diagnostic CT images. Furthermore, the MVCT scan contrast is linear with respect to the electron density of material imaged. MVCT images do not have the same performance characteristics as state-of-the art diagnostic CT scanners when one objectively examines noise and low-contrast resolution. These inferior results may be explained, at least partially, by the low doses delivered by our unit; the dose is 1.1 cGy in a 20 cm diameter cylindrical phantom. In spite of the poorer low-contrast resolution, these relatively low-dose MVCT scans provide sufficient contrast to delineate many soft-tissue structures. Hence, these images are useful not only for verifying the patient's position at the time of therapy, but they are also sufficient for delineating many anatomic structures. In conjunction with the ability to recalculate radiotherapy doses on these images, this enables dose guidance as well as image guidance of radiotherapy treatments.

Computer Systems↗

Calculation and experimental verification of the acoustic stress at GHZ frequencies in SAW resonators.

High power applications of Surface Acoustic Wave (SAW) devices may lead to acoustomigration in their thin metal electrodes, which deteriorates the performance or may even destroy the SAW device. It is confirmed in this paper that the mechanism of acoustomigration is caused by the SAW-induced stress in the metal. The quantitative calculation of this stress will be shown in detail, starting from the widely used P-Matrix model as a standard analysis tool. The combination with the partial wave method (PWM) yields the stress distribution inside the metal. This approach provides the flexibility to determine the stresses for any given point in a SAW device, for any input power, frequency, wavetype, device geometry, or metal layer. In order to confirm the absolute values of the stress components, we calculated and measured displacements as a function of input power and frequency.

Journal Article↗

High-throughput alternative splicing quantification by primer extension and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Alternative splicing is a significant contributor to transcriptome diversity, and a high-throughput experimental method to quantitatively assess predictions from expressed sequence tag and microarray analyses may help to answer questions about the extent and functional significance of these variants. Here, we describe a method for high-throughput analysis of known or suspected alternative splicing variants (ASVs) using PCR, primer extension and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Reverse-transcribed mRNA is PCR amplified with primers surrounding the site of alternative splicing, followed by a primer extension reaction designed to target sequence disparities between two or more variants. These primer extension products are assayed on a MALDI-TOF mass spectrometer and analyzed automatically. This method is high-throughput, highly accurate and reproducible, allowing for the verification of the existence of splicing variants in a variety of samples. An example given also demonstrates how this method can eliminate potential pitfalls from ordinary gel electrophoretic analysis of splicing variants where heteroduplexes formed from different variants can produce erroneous results. The new method can be used to create alternative variant profiles for cancer markers, to study complex splicing regulation, or to screen potential splicing therapies.

Actinin↗

Validity and sensitivity of a pen computer battery of performance tests.

This study compared administration of performance tests and visual analogue scales (VAS) using a newly developed pen computer (PenC) battery with established tests using either pencil-and-paper (PP) or conventional computer. The performance of 47 subjects (23 male, age 18-45 years, weight 51-112 kg) was compared on the two systems after a dose of ethanol (0.8 g/kg up to a maximum of 60 g for males, 50 g for females) or placebo in a double-blind two-period randomized crossover study. Mean (SD) blood ethanol concentrations (breathalyser) were 94.5 mg/100 ml (21.9) at the start of the test battery (30 min post-drink) and 80.2 (13.0) at the end of the battery (75 min post-drink). Ethanol effects were found in all tests, with most outcome measures showing significant slowing or loss of accuracy. Results from the Rapid Visual Information Processing, Sentence Verification and Continuous Attention tasks show that the ethanol-placebo difference and the statistical significance of this difference are in close correspondence for the two modes of administration. The pen computer versions of these tasks may therefore be used as direct replacements for the previous versions. Digit-Symbol and maze tasks did not correspond so closely both showing differences in the speed-accuracy trade-off between the two modes. These tests, however, are sensitive to the effects of ethanol, and may be useful in their own right. Principal component analysis suggested that VAS may be grouped into two factors: (1) 'functional integrity', including measures of alertness and perceived proficiency, and (2) 'mood', including happiness and sociability. Factor 1 showed substantial effects of ethanol, while factor 2 was unchanged. There was close agreement between the results from PP and PenC for both factors as well as for the Sober-Drunk scale, which showed the expected effects of ethanol. Thus pen computer VAS perform in a similar way to the PP versions.

Adolescent↗

Molecular evolution and population genetic analysis of candidate female reproductive genes in Drosophila.

Molecular analyses in several taxa have consistently shown that genes involved in reproduction are rapidly evolving and subjected to positive selection. The mechanism behind this evolution is not clear, but several proposed hypotheses involve the coevolution between males and females. In Drosophila, several male reproductive proteins (Acps) involved in male-male and male-female interactions show evidence of rapid adaptive evolution. What has been missing from the Drosophila literature is the identification and analysis of female reproductive genes. Recently, an evolutionary expressed sequence tag analysis of Drosophila female reproductive tract genes identified 169 candidate female reproductive genes. Many of these candidate genes still await further molecular analysis and independent verification of positive selection. Our goal was to expand our understanding of the molecular evolution of Drosophila female reproductive genes with a detailed polymorphism and divergence study on seven additional candidate female reproductive genes and a reanalysis of two genes from the above study. We demonstrate that 6 candidate female genes of the 9 genes surveyed show evidence of positive selection using both polymorphism and divergence data. One of these proteins (CG17012) is modeled to reveal that the sites under selection fall around and within the active site of this protease, suggesting potential differences between species. We discuss our results in light of potential function as well as interaction with male reproductive proteins.

Animals↗

[The main problems of occupational health in Navarra, 1994-1996].

In 1996 the Navarra Occupational Health Institute, an autonomous technical organization that integrates the functions and means related to occupational health matters, drew up the Occupational Health Diagnosis of Navarra, which is a region characterised by its important industrial sector and its high proportion of small and medium size companies. The results emphasise the high accident rate in the construction sector, the constant increase of professional diseases through "fatigue of tendon pods", as well as the importance of osteo-muscular processes as a cause of temporary and permanent disability. Forty sentinel occupational tumors, mainly mesothelioma, and 27 Obligatory Statement Diseases of occupational origin, mainly brucellosis, were identified in a period of seven years and three years, respectively. Verification was made of a lack of systematised information about population exposure to occupational risks, a scarce development of medical surveillance of exposed workers, and a lack of information about the incidence of occupational injuries in self-employed workers.

English Abstract↗

Antibodies as delivery systems for diagnostic functions.

Antibodies are highly specific targeting agents. Therefore, they are invaluable for in vitro and in vivo diagnostic applications. With the advent of monoclonal antibody technology, the utilization of antibodies has increased dramatically in almost every field of biological sciences. The present review describes the utility of monoclonal antibodies primarily in the cardiovascular diseases. Monoclonal antimyosin antibodies have been developed for noninvasive scintigraphic imaging of equivocal acute myocardial infarction. They have been negative charge modified to provide quicker in vivo visualization of the targeted antibody, as well as being applied for diagnosis of other cardiomyopathies that have disruption of myocardial cell membrane as an obligatory component of the disease. The radiolabeling techniques developed initially for myocardial necrosis imaging have also been applied for imaging of intravascular blood clots and atherosclerotic lesions. The applications of antimyosin, antifibrin and anti-atherosclerotic lesion specific monoclonal antibodies have all achieved initial clinical verification of their efficacy to target the respective lesions. However, to date, only antimyosin has been approved by the FDA for commercialization. Others must await additional studies to unequivocally verify the clinical utilities.

Journal Article↗

Diosmetin Inhibits Bladder Cancer through Suppression of the PI3K-AKT Signaling Pathway and Activation of the p53 Signal Pathway Revealed by Network Pharmacology and In Vitro Experimental Verification.

INTRODUCTION: Diosmetin, a naturally occurring flavonoid abundant in plants such as chrysanthemums, lemons, and oranges, has been reported to exhibit diverse antitumor properties. However, its potential efficacy against bladder cancer remains unexplored. This study aims to investigate the anti-bladder cancer effects of Diosmetin and elucidate the underlying mechanisms using network pharmacology combined with in vitro experiments. METHODS: Public databases were employed to identify shared targets between Diosmetin and bladder cancer. A Protein-Protein Interaction (PPI) network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to predict core targets and signaling pathways. The predicted mechanisms were subsequently validated through in vitro assays. RESULTS: A total of 48 common targets were identified. PPI network analysis revealed 22 hub genes, including AKT1 and MDM2. GO analysis indicated enrichment in 208 biological processes, 23 cellular components, and 38 molecular functions. KEGG analysis suggested that Diosmetin exerts anti-bladder cancer effects primarily through pathways such as Pathways in cancer, PI3K-AKT signaling, and Proteoglycans in cancer. Notably, the PI3K-AKT pathway showed the highest gene enrichment, indicating its potential prominence. In vitro experiments demonstrated that Diosmetin suppresses bladder cancer cell proliferation and induces apoptosis. Additionally, Diosmetin reduced the expression of p-PI3K, p-AKT, and MDM2, while upregulating p53 expression, suggesting involvement of both the PI3K-AKT and p53 pathways. DISCUSSION: These findings align with network pharmacology predictions and highlight the potential of Diosmetin as a multi-target agent against bladder cancer, warranting further in vivo investigation. CONCLUSION: Diosmetin inhibits bladder cancer cell proliferation and promotes apoptosis by suppressing the PI3K-AKT pathway and activating the p53 pathway.

Diosmetin↗

Probabilistic biokinetic modelling of radiocaesium uptake in Arctic seal species: verification of modelled data with empirical observations.

The necessity to provide information about radionuclide concentrations in Arctic marine species has been heightened in recent years due to a number of accidents in Arctic regions involving nuclear vessels and the presence of a large number of potential radioactive contamination sources. The provision for such information is largely dependent on the use of radionuclide uptake and transfer models. The uptake of radionuclides in Arctic seal species in this study has been modelled using a probabilistic biokinetic approach. In this paper, model results are compared with empirical data from relevant samples taken within the Arctic region. Results indicate that the model performs well when estimating concentrations of (137)Cs in two seal species for both median values and reproduction of the distribution of data values, but not as well for a third seal species. Likely factors affecting the results are the probability density functions used for the input parameters.

Animals↗

Assessment of the Lequesne index of severity for osteoarthritis of the hip in an elderly population.

OBJECTIVE: To assess the measurement properties of the Lequesne index of severity for osteoarthritis of the hip (LISOH) together with its overall usefulness with reference to the original stated aims. METHOD: Postal questionnaire was sent to a random sample of 5500 Oxfordshire residents, aged 65 and above. Respondents with hip symptoms at baseline (but without verification of a diagnosis) were sent an identical follow-up questionnaire 12 months later. The questionnaire included a general health section, including the Short Form-36 survey, and a hip section which began with a screening question about hip pain. Respondents who reported having a prolonged episode of hip pain were asked to complete the LISOH. RESULTS: At baseline, response rate of 66.3% (3341/5039) was obtained from eligible participants; 19.2% (610/3175) of respondents reported having hip pain. Internal reliability (Cronbach's alpha) was 0.84 (95% CI: 0.81-0.86) for all 11 items of the LISOH; however, factor analysis identified two factors (sub-scales): "function and mobility" and "pain and discomfort". Rasch analysis revealed that the two factors were only unidimensional when applied to sub-groups of respondents. Convergent validity of the LISOH was questionable, as the "function and mobility" factor was more highly correlated with SF-36 bodily pain score than was the "pain and discomfort" factor. The assessment of sensitivity over time was problematic due to changing patterns of symptomatic weight-bearing joints over time. CONCLUSIONS: The current study identifies major limitations with the LISOH--particularly if used as a single composite measure.

Aged↗

Functional analysis of acid and neutral sphingomyelinases in vitro and in vivo.

The molecular cloning and the elucidation of the gene structures of the acid (aSMase) and a neutral sphingomyelinases (nSMase) of mouse and human facilitated the structural and functional analysis of these enzymes responsible for the catabolism of sphingomyelin present ubiquitously in the membrane lipid bilayer of mammalian cells. The protein and enzymic properties of the glycoprotein aSMase and of a non-glycosylated nSMase residing in the membranes of the endoplasmic reticulum have been analysed in the native as well as in the recombinant shingomyelinases. Important insight was gained from gene targeting experiments in which an aSMase deficient mouse line was generated which mimics the neurovisceral form of the human Niemann-Pick disease. The availability of the cloned aSMase and nSMases discovered so far led to a genetic approach to the verification of the concept that these enzymes in the 'sphingomelin cycle' are responsible for the generation of ceramide regarded as a lipophilic second messenger in the intracellular signal cascades activated by e.g. TNF-alpha, Fas ligand or cellular stress. All the available evidence derived from the aSMase deficient mouse line and several cell lines overexpressing aSMase and nSMase questions a role of ceramide released by the mammalian sphingomyelinases known so far in intracellular signal transduction.

Amino Acid Sequence↗

Rebinding of IgE Fabs at haptenated planar membranes: measurement by total internal reflection with fluorescence photobleaching recovery.

In previous work, a general analytical theory for ligand rebinding at cell surfaces was developed for a reversible bimolecular reaction between ligands in solution and receptors on a membrane surface [Lagerholm, B. C., and Thompson, N. L. (1998) Biophys. J. 74, 1215-1228]. This theory can be used to predict theoretical forms for data obtained by using total internal reflection with fluorescence photobleaching recovery (TIR-FPR) [Thompson, N. L., Burghardt, T. P., and Axelrod, D. (1981) Biophys. J. 33, 435-454]. Thus, one method by which the rebinding theory can be tested is to use TIR-FPR. In the work described herein, the reversible kinetics of mouse monoclonal anti-dinitrophenyl (DNP) IgE Fabs at substrate-supported planar membranes composed of 25 mol % DNP-conjugated phosphatidylethanolamine and 75 mol % dipalmitoylphosphatidylcholine have been examined by using TIR-FPR. Data were obtained as a function of the Fab solution concentration. Higher Fab concentrations reduce rebinding (and increase the fluorescence recovery rate) because different Fab molecules compete for the same surface-binding sites. Data were also obtained for solutions containing different volume fractions of glycerol. In these measurements, higher glycerol concentrations increase rebinding (and decrease the fluorescence recovery rate) because the solution viscosity is increased and the Fab diffusion coefficient in solution is decreased. The TIR-FPR data were quantitatively compared with theoretical predictions which follow from the general theory for rebinding at the membrane surface. The data were consistent with the theoretical predictions and, therefore, provide experimental verification of the previously developed theory.

Animals↗

Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential.

Natural killer cells constitute 50-90% of lymphocytes in human uterine decidua in early pregnancy. Here, CD56(bright) uterine decidual NK (dNK) cells were compared with the CD56(bright) and CD56(dim) peripheral NK cell subsets by microarray analysis, with verification of results by flow cytometry and RT-PCR. Among the approximately 10,000 genes studied, 278 genes showed at least a threefold change with P < or = 0.001 when comparing the dNK and peripheral NK cell subsets, most displaying increased expression in dNK cells. The largest number of these encoded surface proteins, including the unusual lectinlike receptors NKG2E and Ly-49L, several killer cell Ig-like receptors, the integrin subunits alpha(D), alpha(X), beta1, and beta5, and multiple tetraspanins (CD9, CD151, CD53, CD63, and TSPAN-5). Additionally, two secreted proteins, galectin-1 and progestagen-associated protein 14, known to have immunomodulatory functions, were selectively expressed in dNK cells.

CD56 Antigen↗

Italian experience with AutoCapture in conjunction with a membrane lead. Pacesetter Automatic Control of Energy and Membrane Automatic Threshold Evaluation (Pacemate) Study Group.

AutoCapture is a programmable feature of the Pacesetter Microny SR + 2425T VVIR pacemaker, which provides for the automatic capture verification, increase in output in the presence of noncapture and threshold searching, with adjustment of output settings. The effectiveness of this unit in conjunction with the Membrane models 1400T and 1401T bipolar endocardial leads was studied in 54 patients followed at 19 Italian Centers. The patients were randomized at the time of implantation to receive either the model 1400T or the 1401T lead. The electrodes in these leads are covered by a Nafion membrane, which was either impregnated (model 1400T) or not-impregnated (model 1401T) with steroid. This paper reports the data collected over the first six weeks postimplantation. The results of the automatic capture function was compared to the capture threshold measured using the Vario technique at the time of predischarge evaluations, and weeks 1,2, and 6 of postimplant follow-up. The reliability and effectiveness of the pulse generator-lead system allowed for consistent pacing at very low outputs and safety preserved at a programmed output only 0.3 V above the capture threshold.

Aged↗