Home About us Contact
|
Home About us Contact | ||
|
|
||
Excellent Correlation (excellent + correlation)
Selected AbstractsPrediction of Carbonic Anhydrase Activation by Tri-/Tetrasubstituted-pyridinium-azole Compounds: A Computational Approach using Novel Topochemical DescriptorMOLECULAR INFORMATICS, Issue 7 2004Sanjay Bajaj Abstract A novel highly discriminating adjacency-cum-distance based topochemical descriptor, termed as Superadjacency topochemical index, has been derived and its discriminating power investigated with regard to activation of Carbonic anhydrase (CA) isozyme-I by tri-/tetrasubstituted-pyridinium-azole compounds. The new index is not only sensitive to the presence of heteroatoms but also overcomes the problem of degeneracy of many topological descriptors. The discriminating power of Superadjacency topochemical index was found to be far superior when compared with that of distance based Wiener,s index and adjacency based Molecular connectivity index. The values of Wiener,s index, path-one Molecular connectivity index and Superadjacency topochemical index of each of the 42 substituted-pyridinium-azole compounds comprising the dataset were computed. Resultant data was analyzed and suitable models developed after identification of the active ranges. Subsequently, a biological activity was assigned to each of the compounds involved in the dataset using these models, which was then compared with the reported activation constants for Carbonic Anhydrase isozyme-I. Excellent correlations were observed between the activation constants of CA isozyme-I and all the topological/topochemical descriptors. The overall accuracy of prediction was about 91% for models based upon both Molecular connectivity index as well as Wiener,s index, and 96% for model based upon Superadjacency topochemical index. Surprisingly, the accuracy of prediction in the active range was found to be 100% in all the models. Thus the proposed index offers a vast potential for structure-activity/structure-property studies. [source] In Vivo Optical Analysis of Quantitative Changes in Collagen and Elastin During Arterial Remodeling,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005Alexander Christov ABSTRACT Altered collagen and elastin content correlates closely with remodeling of the arterial wall after injury. Optical analytical approaches have been shown to detect qualitative changes in plaque composition, but the capacity for detection of quantitative changes in arterial collagen and elastin content in vivo is not known. We have assessed fluorescence spectroscopy for detection of quantitative changes in arterial composition in situ, in rabbit models of angioplasty and stent implant. Fluorescence emission intensity (FEI) recorded at sites remote from the primary implant site was correlated with immunohistochemical (IH) analysis and extracted elastin and collagen. FEI was significantly decreased (P < 0.05) after treatment with anti-inflammatory agents, and plaque area decreased on comparison with saline-treated rabbits after stent implant or angioplasty (P, 0.013). Excellent correlations for FEI with elastin and collagen I, III and IV content measured by IH (R2, 0.961) analysis were detected by multiple regression (MR) analysis. Good correlations also were found for FEI with elastin and collagen measured by high-performance liquid chromatography; MR analysis provided highly predictive values for collagen and elastin (R2, 0.994). Fluorescence spectroscopic analysis detects quantitative compositional changes in arterial connective tissue in vivo, demonstrating changes at sites remote from primary angioplasty and stent implant sites. [source] Correlation of Tricuspid Annular Velocities With Invasive Hemodynamics in Pulmonary HypertensionCONGESTIVE HEART FAILURE, Issue 4 2007Navin Rajagopalan The authors performed tissue Doppler imaging of the tricuspid annulus in patients with pulmonary hypertension to assess its correlation with invasive indices of right ventricular function. The study population consisted of 32 patients with suspected pulmonary hypertension who underwent pulsed tissue Doppler imaging of the tricuspid annulus and right heart catheterization. Peak systolic (Sa), early diastolic (Ea), and late diastolic (Aa) velocities of the lateral tricuspid annulus were measured and correlated with hemodynamic variables. Peak Sa demonstrated excellent correlation with hemodynamic variables, including cardiac index (r=0.78; P<.001), pulmonary vascular resistance (r=,0.79; P<.001), and transpulmonary gradient (r=,0.72; P<.001). Peak Sa <10 cm/s predicted cardiac index <2.0 L/min/m2 with 89% sensitivity and 87% specificity. In conclusion, tissue Doppler imaging of the tricuspid annulus is a complementary method to assess right ventricular function in pulmonary hypertensive patients. [source] The lower esophageal sphincter strength in patients with gastroesophageal reflux before and after laparoscopic Nissen fundoplicationDISEASES OF THE ESOPHAGUS, Issue 1 2007J. H. Schneider SUMMARY., Lower esophageal sphincter pressure (LESP) and sphincter strength (LESS) were measured before and after short and floppy laparoscopic Nissen fundoplication (LNF) in 38 patients with severe gastro-esophageal reflux disease (GERD). These patients were compared with a control group of 23 healthy volunteers. GERD was assessed by stationary manometry, 24-h pH recordings and endoscopy. LESS was verified by motorized pull-back of an air-filled balloon catheter from the stomach into the esophagus. The catheter assembly was well tolerated by all study participants. LESP increased significantly after operation from 8 mmHg to 14 mmHg (75% of normal values; P < 0.0001), but compared to the control group, LESP (22 mmHg) decreased significantly (P < 0.002). In the control group and in patients with GERD, LESP and LESS showed excellent correlation (r = 0.97, r = 0.94, respectively). After LNF, LESS increased significantly from 0.6 to 1.6 N (P < 0.0001), about 166%. We conclude that the measurement of LESS is able to explain the discrepancy between satisfactory NF operation and the distinct increase of postoperative LESP. The evaluation of LESS is a helpful tool in assessing functional understanding of laparoscopic Nissen fundoplication with a short and floppy wrap. [source] Comparison of LVEF Obtained with Single-Plane RAO Ventriculography and Echocardiography in Patients with and without Obstructive Coronary Artery DiseaseECHOCARDIOGRAPHY, Issue 6 2009Vijayasree Kudithipudi M.D. The left ventricular ejection fraction (LVEF) determined by invasive ventriculography (routine cardiac cath; LV-gram) was compared with that determined by echocardiography in 100 patients scheduled for angiography (86% had LV-gram and 2DE during same hospital admission). Seventy percent of patients had at least single-vessel obstructive coronary artery disease, defined as more than 50% stenosis. By all estimates, the LVEF was higher in patients without coronary artery disease (CAD) compared to patients with CAD. There was an excellent correlation between the LVEF by cath and echo, but this correlation was noticeably less strong in patients with CAD, especially with involvement of the left circumflex artery. (ECHOCARDIOGRAPHY, Volume 26, July 2009) [source] Analysis of Left Atrial Volume Change Rate for Evaluation of Left Ventricular Diastolic FunctionECHOCARDIOGRAPHY, Issue 7 2004F.E.S.C., Ming-Jui Hung M.D. An excellent correlation exists between the change in the left atrial (LA) angiographic area and posterior aortic wall motion. The aim of the study was to define the role of posterior aortic wall motion, indicating LA volume change, during the left ventricular (LV) phase for the assessment of LV diastolic function. A total of 155 patients underwent echocardiography after cardiac catheterization. Study patients were classified into four groups according to the ratio of early-to-late transmitral flow velocity (E/A ratio) and/or LV end-diastolic pressure (EDP): 42 patients with LVEDP < 15 mmHg and E/A ratio >1 (normal filling); 46 patients with E/A < 1 (impaired relaxation); 46 patients with LVEDP , 15 mmHg and E/A > 1 and <2 (pseudonormal filling); 21 patients with E/A > 2, E , 70 cm/s, and E-wave deceleration time ,160 ms (restrictive filling). The slopes of early and late (slopes E and A) diastolic motion of LA wall were derived from M-mode analysis, together with the LV isovolumic time constant Tau from cardiac catheterization. Values of slope E/A decreased in restrictive filling, pseudonormal filling, and impaired relaxation as compared with normal filling (0.41 ± 0.14, 0.69 ± 0.15, and 0.56 ± 0.23 vs 1.25 ± 0.26, P < 0.001, respectively) and correlated inversely with the isovolumic time constant Tau (r = 0.79, P < 0.001). In cases for which a value of slope E/A < 1 was obtained, indicating a relaxation abnormality, the M-mode derived pattern of LA wall motion identified the underlying abnormal LV diastolic function with a sensitivity of 98.3%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 95.2%. Analysis of the slope of LA wall motion, indicating LA volume change rate, during LV diastolic phase is useful in evaluating LV diastolic function. It provides a new noninvasive index that correlates well with invasive index of LV relaxation. [source] Is 3-dimensional volume sonography an effective alternative method to the standard 2-dimensional technique of measuring the nuchal translucency?JOURNAL OF CLINICAL ULTRASOUND, Issue 3 2006Thomas D. Shipp MD Abstract Purpose: To determine whether 3-dimensional (3D) volume scanning is an effective alternative method of measuring nuchal translucency in first-trimester fetuses compared with the standard 2-dimensional (2D) technique, and to report a standardized method of evaluation. Methods: We measured the nuchal translucency of 29 fetuses between 11.4 and 13.9 weeks of age using the standard 2D sonographic technique with the fetus in a sagittal view. We then rescanned the fetus in a coronal orientation and obtained a 3D volume of the fetal neck area from crown to rump using a consistent technique. The sagittal orientation was reconstructed, and the width of the nuchal translucency was measured electronically using the reconstructed midsagittal view. The measurements using a conventional 2D sagittal view were then compared with the 3D reconstructed sagittal view. The nuchal translucency was adequately measured in all fetuses in which the 3D assessment was attempted. Results: The nuchal translucencies of 29 consecutive fetuses were measured using both 2D and 3D multiplanar reconstruction of the fetal neck. The mean ± standard deviation for the standard 2D assessment of the nuchal translucency was 1.7 ± 1.4 mm. Using 3D reconstruction of the Z plane, the measurement was 1.8 ± 1.6 mm. This was not a statistically significant difference (P = 0.4). There was a very high correlation between the two techniques (r = 0.984, P < 0.001). Conclusions: There is an excellent correlation between the measurements of the nuchal translucency using standard 2D scanning and those obtained from 3D multiplanar reconstruction of the Z plane. Using a consistent technique, the nuchal translucency can be accurately and reliably measured with a 3D rendering. This technique is potentially useful in fetuses that are not in an optimal position for standard 2D nuchal translucency measurement. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:118,122, 2006 [source] Antioxidant Properties of Edible Basidiomycete,Phellinus igniarius,in Submerged CulturesJOURNAL OF FOOD SCIENCE, Issue 1 2010Ming Yeou Lung ABSTRACT:, Dried mycelia and mycelia-free broths produced by submerged cultures of,Phellinus igniarius,under optimal culture conditions were extracted using methanol and hot water and investigated for antioxidant properties. Methanolic extracts from dried mycelia (MEM) and mycelia-free broth (MEB) showed significant antioxidant properties for all EC50 values less than 10 mg/mL except for MEB in scavenging effects on DPPH radicals. Hot water extracts from dried mycelia (HWEM) were evidenced by their low EC50 values (<10 mg/mL) to be effective in reducing power, chelating effect on ferrous ions, and scavenging effect on superoxide anions. ,-tocopherol was mainly found in MEM and ,-tocopherol in MEB. Ascorbic acid and total flavonoids were abundant in methanolic extracts (MEM + MEB), whereas total phenols were rich in HWEM. An excellent correlation between contents of total phenols and EC50 values was accomplished for antioxidant activity (R2= 0.996) and chelating ferrous ions ability (R2= 0.922). Practical Application: In our paper, the products by submerged culture of,Phellinus igniarius,exhibited powerful antioxidant properties. Results told that extracts from fermenting products by,P. igniarius,might be good sources for antioxidant-related functional foods and pharmaceutical industries. [source] Assessment of Relationships between Sensory and Instrumental Quality of Controlled-atmosphere-stored ,Fuji' Apples by Multivariate AnalysisJOURNAL OF FOOD SCIENCE, Issue 9 2004G. Echeverría ABSTRACT: Physicochemical parameters, sensory attributes, and total aroma emission of ,Fuji' apples (Malus×domestica Borkh.) were studied in relation to storage conditions, storage duration, and shelf life period. Commercially ripe fruit were analyzed after 3, 5, and 7 mo of cold storage in normal atmosphere (AIR) (210 L/m3 O2+ 0.3 L/m3 CO2) or under 3 different controlled atmosphere (CA) treatments (10 L/m3 O2+ 10 L/m3 CO2, 20 L/m3 O2+ 20 L/m3 CO2, or 10 L/m3 O2+ 30 L/m3 CO2), after which apples were kept at 20 °C for 1, 5, and 10 d. Data were subjected to partial least square regression (PLSR) analysis. Physicochemical parameters were well preserved throughout storage, especially in CA-stored apples; however, these apples showed lower total aroma emission. Sensory acceptability was also higher for CA-stored fruit after 7 mo of storage, whereas no significant differences were found for shorter storage periods. Accordingly, greater scores in sensory firmness, sensory flavor, sensory acidity, and appearance were observed for fruit stored in 10 L/m3 O2+ 10 L/m3 CO2 after long storage. Two PLSR models were established, 1 for relating physicochemical parameters to overall acceptability, and another for assessing the correlation between sensory acidity and instrumentally measured titratable acidity. The 1st PLSR model indicated that soluble solids concentration, titratable acidity, flesh firmness, and background color of the shaded side have a positive influence on acceptability. The 2nd model indicated that sensory acidity also showed an excellent correlation to instrumentally measured titratable acidity. [source] Quantification of hepatic steatosis with MRI: The effects of accurate fat spectral modelingJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2009Scott B. Reeder MD Abstract Purpose To develop a chemical-shift,based imaging method for fat quantification that accounts for the complex spectrum of fat, and to compare this method with MR spectroscopy (MRS). Quantitative noninvasive biomarkers of hepatic steatosis are urgently needed for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD). Materials and Methods Hepatic steatosis was measured with "fat-fraction" images in 31 patients using a multiecho chemical-shift,based water-fat separation method at 1.5T. Fat-fraction images were reconstructed using a conventional signal model that considers fat as a single peak at ,210 Hz relative to water ("single peak" reconstruction). Fat-fraction images were also reconstructed from the same source images using two methods that account for the complex spectrum of fat; precalibrated and self-calibrated "multipeak" reconstruction. Single-voxel MRS that was coregistered with imaging was performed for comparison. Results Imaging and MRS demonstrated excellent correlation with single peak reconstruction (r2 = 0.91), precalibrated multipeak reconstruction (r2 = 0.94), and self-calibrated multipeak reconstruction (r2 = 0.91). However, precalibrated multipeak reconstruction demonstrated the best agreement with MRS, with a slope statistically equivalent to 1 (0.96 ± 0.04; P = 0.4), compared to self-calibrated multipeak reconstruction (0.83 ± 0.05, P = 0.001) and single-peak reconstruction (0.67 ± 0.04, P < 0.001). Conclusion Accurate spectral modeling is necessary for accurate quantification of hepatic steatosis with MRI. J. Magn. Reson. Imaging 2009;29:1332,1339. © 2009 Wiley-Liss, Inc. [source] Multicomponent mass transport model for the sorption of metal ions on bone charAICHE JOURNAL, Issue 9 2004Danny C. K. Ko Abstract The sorption of binary mixtures of copper/cadmium and copper/zinc ions onto bone char was studied in fixed beds. The effects of solution flow rate, initial dye concentration, and bone char particle size range were investigated. A mass transport model based on film-surface diffusion and the IAS model for the equilibrium relationship was used to develop theoretical fixed-bed breakthrough curves. The model incorporates the Sips isotherm for the first time in fixed-bed predictions, since this isotherm gives an excellent correlation of the experimental equilibrium data. The model was used to determine the optimum surface diffusivities as 7.37 × 10,10 and 2.73 × 10,9 cm2/s for copper and cadmium in the Cu/Cd system; and 1.61 × 10,9 and 2.43 × 10,9 cm2/s for copper and zinc in the Cu/Zn system. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2130,2141, 2004 [source] Controlled Transdermal Delivery of Propranolol Using HPMC Matrices: Design and In-vitro and In-vivo EvaluationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2000P. R. P. VERMA To improve bioavailability and achieve a smoother plasma-concentration profile as compared with oral administration, a matrix-dispersion-type transdermal delivery system was designed and developed for propranolol using different ratios of hydroxypropyl-methylcellulose (HPMC) K4M, K15M and K100M. Formulations were evaluated for in-vitro dissolution characteristics using a Cygnus' sandwich-patch holder. Drug release followed Higuchi rather than zero-order or first-order kinetics. In-vivo evaluation was carried out on healthy volunteers (21 ± 1.41 years; 60.89 ± 5.35 kg) following the balanced incomplete block design. The dissolution rate constant (k) and data generated from plasma and urine (Cmax, maximum plasma concentration; tmax, time to reach peak plasma concentration; AUC, area under the curve; ke, elimination rate constant; t½e, elimination half-life; ka, absorption rate constant; t½a, absorption half-life) were evaluated statistically by two-way analysis of variance. Statistically excellent correlation was found between the percentage of drug absorbed and Cmax, AUC0,24 and AUC0-,. A highly significant difference (P < 0.001) was observed when Cmax and AUC0-, generated from plasma and urine were compared, but ke, t½e, ka and t½a did not differ significantly (P > 0.1). We conclude that urinary excretion data may be used as a simpler alternative to blood level data in studying the kinetics of absorption and deriving the absorption parameters. [source] Multidimensional GC coupled to MS for the simultaneous determination of oxygenate compounds and BTEX in gasolineJOURNAL OF SEPARATION SCIENCE, JSS, Issue 4-5 2010Danilo Sciarrone Abstract In the present work, carried out in relation to the European and American Directives on the quality of petrol and diesel fuels, the simultaneous determination of the oxygenate compounds and BTEX in gasoline was achieved through the use of a multidimensional GC (MDGC)/MS system, employing a Deans switch-based transfer system, with an innovative configuration; the latter enabled multiple heart-cut transfers with no hint of retention time shift, a phenomenon that can occur in MDGC, providing the possibility to achieve more then 20 different heart-cuts for the compounds of interest. In this study, 20 selected compounds were quantitatively transferred with 12 heart-cuts, from a first to a secondary column, in order to resolve primary column co-elutions. Analyte quantification and identification was achieved through a fast-scanning quadrupole mass analyzer, operated in full scan mode, in order to evaluate also the interfering compounds transferred together with the compounds of interest. The multidimensional method developed was subjected to validation. All attained data were in excellent correlation with results obtained through the UNI-EN 12177:2000, ASTM D 5580-02 and ASTM D 4815-04 MDGC methods, for the determination of benzene, BTEX and oxygenate compounds in gasoline, respectively. [source] Comparison of measurements of 18 analytes in canine and feline blood samples using the in-practice Falcor 350 and the reference KoneLab 30i analysersJOURNAL OF SMALL ANIMAL PRACTICE, Issue 10 2008K. Papasouliotis Objectives: Falcor 350 (A. Menarini Diagnostics) is a wet-reagent biochemistry analyser that is available for in-house use. The aim of this study was to compare the results produced by this analyser with those obtained by a wet-reagent analyser (KoneLab 30i; Thermo Clinical Labsystems) that served as the reference instrument. Methods: Blood samples from 120 clinical cases (60 dogs and 60 cats) were analysed for 18 analytes (urea, creatinine, total proteins, albumin, creatine kinase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, amylase, lipase, glucose, triacylglycerol, cholesterol, total calcium, phosphate, sodium and potassium) using both the reference and Falcor instruments. Results: Good to excellent correlations (rs value) (canine/feline) were identified for urea (0·87/0·86), creatinine (0·96/0·99), total proteins (0·91/0·95), albumin (0·96/0·93), creatine kinase (0·98/0·99), aspartate aminotransferase (0·95/0·98), alanine aminotransferase (0·99/0·99), alkaline phosphatase (0·99/0·98), total bilirubin in dogs (0·88), amylase (0·99/0·87), lipase in dogs (0·88), glucose (0·97/0·98), triacylglycerol (0·93/0·97), cholesterol (0·99/0·99), total calcium (0·88/0·89), phosphate (0·94/0·97) and potassium (0·96/0·97). The correlations for sodium (0·41/0·61), total bilirubin in cats (0·78) and lipase in cats (0·25) were considered unacceptable. Clinical Significance: For 13 of the 18 analytes (creatinine, total proteins, albumin, creatine kinase, aspartate aminotransferase, alanine aminotransferase, amylase, glucose, cholesterol, triacylglycerol, phosphate, potassium and urea) in both canine and feline samples, the two instruments produce values that are closely related to each other (excellent correlation) and are sufficiently similar to allow them to be used interchangeably without the need for additional correction factor computations (good agreement). Because of differences in the methodologies, the Falcor results for alkaline phosphatase, total calcium, sodium, lipase and total bilirubin cannot be used interchangeably with those generated by the KoneLab and should be interpreted using reference intervals established from the Falcor analyser. [source] Analysis of canine and feline haemograms using the VetScan HMT analyserJOURNAL OF SMALL ANIMAL PRACTICE, Issue 10 2003E. C. Dewhurst The VetScan HMT is an impedance counter haematology analyser which produces a full blood count and three-part white blood cell differential. The aim of this study was to compare the results generated by the analyser with those obtained by standard methods used routinely in the authors'laboratory. Blood samples from 68 dogs and 59 cats were run on the VetScan HMT analyser and also subjected to reference methods, and the results obtained were compared. Correlation coefficients (feline/canine) were: 0·97/0·99 for haematocrit (Hct), 0*middot;98/0·99 for haemoglobin (Hb), 0·81/0·98 for total white blood cells (WBC), and 0·89/0·97 for granulocyte and 0·65/0·93 for platelet counts. Coefficients for lymphocyte counts were 0·25/0·28 and for monocyte counts were 0·12/0·79. In conclusion, the VetScan HMT performed well on canine samples, showing excellent correlation for canine Hct, Hb, RBC, WBC, granulocyte and platelet counts. For feline samples, although there was excellent correlation for Hct, Hb and RBC, the WBC and three-part white blood cell differential and platelet count should be interpreted with caution as they can be unreliable. [source] Validation of the Wong-Baker FACES Pain Rating Scale in Pediatric Emergency Department PatientsACADEMIC EMERGENCY MEDICINE, Issue 1 2010Gregory Garra DO Abstract Objectives:, The Wong-Baker FACES Pain Rating Scale (WBS), used in children to rate pain severity, has been validated outside the emergency department (ED), mostly for chronic pain. The authors validated the WBS in children presenting to the ED with pain by identifying a corresponding mean value of the visual analog scale (VAS) for each face of the WBS and determined the relationship between the WBS and VAS. The hypothesis was that the pain severity ratings on the WBS would be highly correlated (Spearman's rho > 0.80) with those on a VAS. Methods:, This was a prospective, observational study of children ages 8,17 years with pain presenting to a suburban, academic pediatric ED. Children rated their pain severity on a six-item ordinal faces scale (WBS) from none to worst and a 100-mm VAS from least to most. Analysis of variance (ANOVA) was used to compare mean VAS scores across the six ordinal categories. Spearman's correlation (,) was used to measure agreement between the continuous and ordinal scales. Results:, A total of 120 patients were assessed: the median age was 13 years (interquartile range [IQR] = 10,15 years), 50% were female, 78% were white, and six patients (5%) used a language other than English at home. The most commonly specified locations of pain were extremity (37%), abdomen (19%), and back/neck (11%). The mean VAS increased uniformly across WBS categories in increments of about 17 mm. ANOVA demonstrated significant differences in mean VAS across face groups. Post hoc testing demonstrated that each mean VAS was significantly different from every other mean VAS. Agreement between the WBS and VAS was excellent (, = 0.90; 95% confidence interval [CI] = 0.86 to 0.93). There was no association between age, sex, or pain location with either pain score. Conclusions:, The VAS was found to have an excellent correlation in older children with acute pain in the ED and had a uniformly increasing relationship with WBS. This finding has implications for research on pain management using the WBS as an assessment tool. ACADEMIC EMERGENCY MEDICINE 2010; 17:50,54 © 2009 by the Society for Academic Emergency Medicine [source] Individualized population pharmacokinetic model with limited sampling for cyclosporine monitoring after liver transplantation in clinical practiceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2007P. LANGERS Summary Background, We recently developed and validated limited sampling models (LSMs) for cyclosporine monitoring after orthotopic liver transplantation based on individualized population pharmacokinetic models with Bayesian modelling. Aim, To evaluate LSM in practice, and to seek optimal balance between benefit and discomfort. Methods, In 30 stable patients, more than 6 months after orthotopic liver transplantation, previously switched from trough- to 2 h post-dose (C2)-monitoring, we switched to 3-monthly LSM 0,1,2,3 h-monitoring. During 18 months we evaluated dose, creatinine clearance, calculated area under the curve, intra-patient pharmacokinetic variability and ability to assess systemic exposure by several previously validated LSMs. Results, Within patients, there was variability of cyclosporine-area under the curve with the same dose (CV of 15%). Compared to C2-monitoring, there was no significant difference in dose (P = 0.237), creatinine clearance (P = 0.071) and number of rejections. Some models showed excellent correlation and precision with LSM 0,1,2,3 h comparing area under the curves (0,2 h: r2 = 0.88; 0,1,3 h: r2 = 0.91; 0,2,3 h: r2 = 0.92, all P < 0.001) with no difference in advised dose. Conclusions, The limited sampling model, with only trough- and 2-h sampling, yields excellent accuracy and assesses systemic exposure much better than C2 with less bias and greater precision. Considering the calculated intra-patient variability, more precision is redundant, so LSM 0,2 h seems the optimal way of cyclosporine-monitoring. [source] SESAME-HSQC for simultaneous measurement of NH and CH scalar and residual dipolar couplings,MAGNETIC RESONANCE IN CHEMISTRY, Issue 4 2007Peter Würtz Abstract We present a novel pulse sequence, SESAME-HSQC, for the simultaneous measurement of several NH and CH scalar and residual dipolar couplings in double labeled proteins. The proposed Spin-statE Selective All Multiplicity Edited (SESAME)-HSQC combines gradient selected and sensitivity enhanced 15N- and constant-time 13C-HSQC experiments with the recently introduced spin-state selective method (Nolis et al., J. Magn. Reson. 180 (2006) 39,50) for measuring couplings simultaneously at amide and aliphatic regions. Excellent resolution and high sensitivity is warranted by removing all coupling interactions during the indirectly detected t1 period, and by employing pulsed field gradients for coherence selection and utilizing coherence order selective spin-state selection. The scalar and residual dipolar couplings can be readily measured from a two-dimensional 15N/13C-HSQC spectrum without additional spectral crowding. SESAME-HSQC can be used for epitope mapping by observing chemical shift changes in both amide and aliphatic regions. Simultaneously, potential conversion in protein conformation can be probed by analyzing changes in residual dipolar couplings induced by ligand binding. The pulse sequence is experimentally verified with a sample of 15N/13C enriched human ubiquitin. The internuclear vector directions determined from the residual dipolar couplings are found to be in excellent correlation with those predicted from ubiquitin's refined solution structure. Copyright © 2007 John Wiley & Sons, Ltd. [source] Dynamic oxygen-enhanced MRI reflects diffusing capacity of the lungMAGNETIC RESONANCE IN MEDICINE, Issue 6 2002Yoshiharu Ohno Abstract The purpose of this study was to demonstrate the feasibility of dynamic oxygen-enhanced MRI in a clinical setting. We hypothesized that dynamic oxygen enhancement can reflect the regional diffusing capacity of the lung. Ten patients with pulmonary emphysema and seven healthy volunteers were examined with a respiratory-synchronized inversion recovery single-shot turbo spin-echo sequence (TR = 3200,5000 ms, TE = 16 ms, TI = 720 ms, ETS = 4 ms) following 100% oxygen inhalation, using a 1.5 T whole-body scanner. Maximum mean relative enhancement ratios calculated by averaging six defined regions of interest (ROIs) in both lungs were statistically compared between healthy volunteers and patients, and were correlated with diffusing lung capacity (%DLCO). In patients with pulmonary emphysema, maximum mean relative enhancement ratios were significantly decreased compared to those in healthy volunteers (P = 0.0008). Maximum mean relative enhancement ratio had excellent correlation with % DLC0 (r2 = 0.83). Dynamic oxygen-enhanced MRI may reflect the diffusing capacity of the lung; therefore, imaging of oxygen enhancement with MRI may provide maps of the diffusing capacity. Magn Reson Med 47:1139,1144, 2002. © 2002 Wiley-Liss, Inc. [source] Analytical design of a half-mode substrate integrated waveguide Wilkinson power dividerMICROWAVE AND OPTICAL TECHNOLOGY LETTERS, Issue 5 2010A. Suntives Abstract This article presents a new approach in designing half-mode substrate integrated waveguide Wilkinson power dividers based on analytical relations. Even- and odd-mode analysis is used to determine the required value of the branch resistance and optimize the power divider performance, namely the output ports' isolation. In this manner, the design process for this microwave component is simplified and expedited, while an excellent correlation with full-wave simulations is maintained. Measurements of the fabricated prototype corroborate the calculated results and demonstrate a wide output-port isolation bandwidth of 71%. © 2010 Wiley Periodicals, Inc. Microwave Opt Technol Lett 52: 1066,1069, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.25145 [source] 3D Pharmacophore Model for Insect Repellent Activity and Discovery of New Repellent CandidatesMOLECULAR INFORMATICS, Issue 5 2005Apurba Abstract To better understand the mechanism of insect repellency and to identify new repellent candidates, we performed a three-dimensional quantitative structure-activity (QSAR) study and developed a pharmacophore model for potent repellent activity from a set of eleven known diverse insect repellent compounds by using the CATALYST 3D-QSAR methodology. The protection time for repellent activity of the compounds was taken from an earlier published study. The pharmacophore was found to have three hydrophobic sites (two aliphatic and one aromatic) and a hydrogen-bond acceptor site in specific locations in the three dimensional geometry of the molecules that are critical for potent repellent activity. The pharmacophore showed an excellent correlation (correlation=0.9) between the experimental protection time afforded by the compounds in the training set and their predicted protection time. The validity of the pharmacophore model goes beyond the list in the training set and is found to map well on a variety of other insect repellents. By mapping this model on one of the more potent analogue we have generated a three-dimensional shape based template which allowed a search of our in-house compound database and discover four new potential insect repellent candidates. [source] A proteomic analysis of penicillin resistance in Streptococcus pneumoniae reveals a novel role for PstS, a subunit of the phosphate ABC transporterMOLECULAR MICROBIOLOGY, Issue 5 2005Hafid Soualhine Summary Resistance to penicillin is widespread in the Gram-positive bacterium Streptococcus pneumoniae, and while several mutations are known to be implicated in resistance other mechanisms are likely to occur. We used a proteomic screen of two independent mutants in which resistance was selected in vitro. We found a number of differentially expressed proteins including PstS, a subunit of the phosphate ABC transporter of S. pneumoniae. This protein was increased in both mutants, a phenotype correlated to increased RNA expression of the entire phosphate ABC transporter operon. Inactivation of the pstS gene led to increased susceptibility to penicillin in the wild-type strain. To further link the expression of the ABC phosphate transporter with penicillin resistance, we looked at pstS mRNA levels in 12 independent clinical isolates sensitive and resistant to penicillin and found an excellent correlation between resistance and increased expression of pstS. Inactivation of pstS in one of the clinical isolates significantly reduced penicillin resistance. Global approaches are ideally suited for the discovery of novel factors in the biology of resistance. [source] A census of the Carina Nebula , II.MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2007Energy budget, global properties of the nebulosity ABSTRACT The first paper in this series took a direct census of energy input from the known OB stars in the Carina Nebula, and in this paper we study the global properties of the surrounding nebulosity. This detailed comparison may prove useful for interpreting observations of extragalactic giant H ii regions and ultraluminous infrared (IR) galaxies. We find that the total IR luminosity of Carina is about 1.2 × 107 L,, accounting for only about 50,60 per cent of the known stellar luminosity from Paper I. Similarly, the ionizing photon luminosity derived from the integrated radio continuum is about 7 × 1050 s,1, accounting for ,75 per cent of the expected Lyman continuum from known OB stars. The total kinetic energy of the nebula is about 8 × 1051 erg, or ,30 per cent of the mechanical energy from stellar winds over the lifetime of the nebula, so there is no need to invoke a supernova (SN) explosion based on energetics. Warm dust grains residing in the H ii region interior dominate emission at 10,30 ,m, but cooler grains at 30,40 K dominate the IR luminosity and indicate a likely gas mass of ,106 M,. We find an excellent correlation between the radio continuum and 20,25 ,m emission, consistent with the idea that the ,80-K grain population is heated by trapped Ly, photons. Similarly, we find a near perfect correlation between the far-IR optical depth map of cool grains and 8.6-,m hydrocarbon emission, indicating that most of the nebular mass resides as atomic gas in photodissociation regions and not in dense molecular clouds. Synchronized star formation around the periphery of Carina provides a strong case that star formation here was indeed triggered by stellar winds and ultraviolet radiation. This second generation appears to involve a cascade toward preferentially intermediate- and low-mass stars, but this may soon change when , Carinae and its siblings explode. If the current reservoir of atomic and molecular gas can be tapped at that time, massive star formation may be rejuvenated around the periphery of Carina much as if it were a young version of Gould's Belt. Furthermore, when these multiple SNe occur, the triggered second generation will be pelted repeatedly with SN ejecta bearing short-lived radioactive nuclides. Carina may therefore represent the most observable analogue to the cradle of our own Solar system. [source] Normal ranges of angiogenesis regulatory proteins in human platelets,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Jon E. Peterson Platelets sequester angiogenesis regulatory proteins early in tumor growth, which suggests a new avenue for monitoring disease. To date, there are no clinically relevant reference ranges for markers of early angiogenesis. We introduce a new ELISA-based method for accurate and reproducible measurement of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1), fibroblast growth factor, basic (bFGF), and endostatin in platelets. To facilitate clinical applicability, the platelet levels in isolated samples were determined utilizing a new actin ELISA method. Platelets from healthy donors at single and repetitive time points were used for the assessment of normal ranges of these proteins. The physiological levels in platelets were: VEGF (0.74 ± 0.37 pg/106 platelets); PDGF (23 ± 6 pg/106); PF4 (12 ± 5 ng/106); TSP-1 (31 ± 12 ng/106); bFGF (0.44 ± 0.15 pg/106); and endostatin (5.6 ± 3.0 pg/106). There was an excellent correlation (R2 = 0.7) between the platelet levels calculated with the actin ELISA and complete blood count. The levels of the platelets were higher than those in platelet-poor plasma by factors of: VEGF (215-fold); PDGF (914-fold); PF-4 (516-fold); TSP-1 (813-fold); and bFGF (17-fold). The endostatin levels were nearly equivalent. The biovariability of the platelet proteins in eight healthy subjects over a 5-week period was found to be minimal. We describe accurate and direct measurements of the concentrations of VEGF, bFGF, PDGF, TSP-1, endostatin, and PF4 in platelets of healthy human subjects. In contrast to the highly variable levels in plasma and serum, the platelet-derived measurements were accurate and reproducible with minimal biovariability. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Comparison of different near-infrared spectroscopic cerebral oxygenation indices with central venous and jugular venous oxygenation saturation in childrenPEDIATRIC ANESTHESIA, Issue 2 2008NICOLE NAGDYMAN Summary Background:, We compared two different near-infrared spectrophotometers: cerebral tissue oxygenation index (TOI) measured by NIRO 200 and regional cerebral oxygenation index (rSO2) measured by INVOS 5100 with venous oxygen saturation in the jugular bulb (SjO2) and central SvO2 from the superior caval vein (SVC) during elective cardiac catheterization in children. Methods:, A prospective observational clinical study in 31 children with congenital heart defects in a catheterization laboratory was undertaken. TOI was compared with SjO2 in the left jugular bulb and with SvO2. rSO2 was compared with SjO2 from the right jugular bulb and SvO2. Linear regression analysis and Pearson's correlation coefficient were calculated and Bland,Altman analyses were performed. Results:, Cerebral TOI and SjO2 were significantly correlated (r = 0.56, P < 0.0001), as well as TOI and SvO2 with r = 0.74 (P < 0.0001). Bland,Altman plots showed a mean bias of ,4.3% with limits of agreement of 15.7% and ,24.3% for TOI and SjO2 and a mean bias of ,4.9% with limits of agreement of 10.3% and ,20.1% for TOI and SvO2. Cerebral rSO2 and SjO2 showed a significant correlation (r = 0.83, P < 0.0001) and rSO2 and SvO2 showed excellent correlation with r = 0.93 (P < 0.0001). Bland,Altman plots showed a mean bias of ,5.2% with limits of agreement of between 8.4% and ,18.8% for rSO2 and SjO2 and a mean bias of 5.6% with limits of agreement of 13.4% and ,2.2% for rSO2 and SvO2. Conclusions:, Both near-infrared spectroscopy devices demonstrate a significant correlation with SjO2 and SvO2 values; nevertheless both devices demonstrate a substantial bias of the measurements to both SjO2 and SvO2. [source] GaN HEMT thermal behavior and implications for reliability testing and analysisPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 6 2008Daniel S. Green Abstract GaN HEMT reliability evaluation in a typical Arrhenius manner requires establishing peak junction temperature for a particular stress condition. Several new techniques have yielded promising results toward establishing peak temperature for these devices in combination with detailed physical modeling, particularly micro-Raman imaging. This paper compares results from finite element modeling to measurements by infrared imaging and micro-Raman imaging. The limitations of IR imaging were confirmed similar to earlier reports. Two techniques for establishing temperature from micro-Raman measurements were used to reveal excellent correlation to the model, and also provide insight into the relationship between temperature and structural change in the device. Temperature modeling data is reported for base plate temperature from 85°C to 250°C for practical GaN HEMT devices. Implications of the measurements for GaN HEMT reliability stress testing and analysis will be discussed. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] The role of aluminium and titanium in the point defects of gamma irradiated natural quartzPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 1 2005G. O. Sawakuchi Abstract In this work, the origin of the smoky colour acquired by quartz when exposed to extremely high doses (20 kGy) of ionising radiation is studied. Five paramagnetic centres were detected in the electron paramagnetic resonance (EPR) spectrum of irradiated quartz: [AlO4]0, [TiO4,/Li+]0A, [GeO4,/Na+]0A, [GeO4,/Li+]0C, and E,1. Optical absorption revealed a complex spectrum with superposition of bands. With the technique of thermoluminescence, at least three peaks at around 180, 260 and 320 °C were detected. The peak at around 180 ºC has maximum emission at 470 nm and the peaks at around 260 and 320 °C have maximum emissions at 450 nm. Through correlations between the obtained results with these techniques, it was possible to confirm previous results from the literature, i.e., that the smoky colour of quartz is strongly related to the centre [AlO4]0. Besides, it was verified an excellent correlation between the thermal decay of [AlO4]0 and [TiO4,/Li+]0A, suggesting that at a temperature around 200 ºC the Li leaves the Ti centre and recombines with the aluminium centre destroying the smoky colour of irradiated quartz. On the other hand and differently from the literature this process does not correlate to any of the thermoluminescence peaks. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Extracting metabolite ions out of a matrix background by combined mass defect, neutral loss and isotope filtrationRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 2 2009Filip Cuyckens Mass defect, neutral loss and isotope filtration techniques were applied to electrospray ionization mass spectrometry (ESI-MS) data obtained for in vivo and in vitro samples of drug metabolism studies. A combination of these post-acquisition processing techniques was shown to be more powerful than the use of one of these tools alone for the detection in complex matrices of metabolites of candidate drugs with a characteristic isotope pattern (e.g. containing bromine, chlorine, or a high proportion of radiolabeled drug (12C/14C)) or characteristic neutral losses. In combination with ,all-in-one' data acquisition this methodology is able to perform software-driven constant neutral loss scanning for an unlimited number of mass differences at any time after analysis. Highly selective MS chromatograms were obtained with excellent correlation with their corresponding radiochromatograms. Copyright © 2009 John Wiley & Sons, Ltd. [source] Quantitative analysis of amyloid , peptides in cerebrospinal fluid of Alzheimer's disease patients by immunoaffinity purification and stable isotope dilution liquid chromatography/negative electrospray ionization tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2006Tomoyuki Oe The 40 and 42 amino-acid residue forms of amyloid beta (A,1,40 and A,1,42) in cerebrospinal fluid (CSF) have been proposed as potential biomarkers of Alzheimer's disease (AD). Quantitative analyses of A, peptides in CSF have relied almost exclusively on the use of immunoassay-based assays such as the enzyme-linked immunosorbent assay (ELISA) procedure. However, due to the ability of the A, peptides to readily self-aggregate or bind to other proteins and glassware, such analyses are extremely challenging. Analyses are further complicated by the potential of the peptides to undergo post-translational modifications and the possibilities for cross-reaction in the ELISA assays with endogenous components of the CSF. An approach based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) has now been developed which overcomes these methodological issues. The key steps in implementing this new approach involved immunoaffinity purification coupled with the use of [15N]-labeled A, peptides as internal standards, a basic LC mobile phase, negative ion electrospray ionization, and a basic solvent for dissolving the peptides and washing the injection needle to prevent carryover of analytes during multiple injections on the LC/MS system. The validated method had limits of quantitation of 44,fmol/mL (200,pg/mL) for A,1,42 and 92,fmol/mL (400,pg/mL) for A,1,40. An excellent correlation was found between the LC/MS/MS assay and an ELISA assay for A,1,42 in human CSF (r2,=,0.915), although less correlation was observed for A,1,40 (r2,=,0.644). Mean CSF A,1,42 concentrations for samples collected 2 weeks apart from a limited number of AD patients provided additional confidence in the reproducibility of the LC/MS/MS assay. Concentrations for duplicate samples from AD patients were slightly higher than most previously reported values (mean 1.06,±,0.25,ng/mL; n,=,7). A,1,40 concentrations in duplicate samples obtained from AD patients were also reproducible but were found to be slightly lower than most previously reported values (mean 6.36,±,3.07,ng/mL; n,=,7). Consistent with literature reports, mean A,1,42 concentrations were found to be lower in AD patients compared with the normal subjects (mean 1.49,±,0.59,ng/mL; n,=,7), whereas there was no difference in A,1,40 concentrations between AD patients and normal subjects (mean 5.88,±,3.03,ng/mL; n,=,7). The accuracy and precision of the LC/MS assay mean that it will be a useful complement to existing ELISA assays for monitoring therapeutic interventions designed to modulate CSF A,1,42 concentrations in individual AD patients. Moreover, the introduction of stable isotope labeled internal standards offers the potential to achieve a more rigorous account of the influence of methodological effects related to sample collection and processing. Copyright © 2006 John Wiley & Sons, Ltd. [source] Structural improvement of unliganded simian immunodeficiency virus gp120 core by normal-mode-based X-ray crystallographic refinementACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2009Xiaorui Chen The envelope protein gp120/gp41 of simian and human immunodeficiency viruses plays a critical role in viral entry into host cells. However, the extraordinarily high structural flexibility and heavy glycosylation of the protein have presented enormous difficulties in the pursuit of high-resolution structural investigation of some of its conformational states. An unliganded and fully glycosylated gp120 core structure was recently determined to 4.0,Å resolution. The rather low data-to-parameter ratio limited refinement efforts in the original structure determination. In this work, refinement of this gp120 core structure was carried out using a normal-mode-based refinement method that has been shown in previous studies to be effective in improving models of a supramolecular complex at 3.42,Å resolution and of a membrane protein at 3.2,Å resolution. By using only the first four nonzero lowest-frequency normal modes to construct the anisotropic thermal parameters, combined with manual adjustments and standard positional refinement using REFMAC5, the structural model of the gp120 core was significantly improved in many aspects, including substantial decreases in R factors, better fitting of several flexible regions in electron-density maps, the addition of five new sugar rings at four glycan chains and an excellent correlation of the B -factor distribution with known structural flexibility. These results further underscore the effectiveness of this normal-mode-based method in improving models of protein and nonprotein components in low-resolution X-ray structures. [source] | |||||||||||||||||||||||||||||||