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PubMed2003

Moving window two-dimensional correlation spectroscopy and determination of signal-to-noise threshold in correlation spectra.

In this paper we report two new developments in two-dimensional (2D) correlation spectroscopy; one is the combination of the moving window concept with 2D spectroscopy to facilitate the analysis of complex data sets, and the other is the definition of the noise level in synchronous/asynchronous maps. A graphical criterion for the latter is also proposed. The combination of the moving window concept with correlation spectra allows one to split a large data matrix into smaller and simpler subsets and to analyze them instead of computing overall correlation. A three-component system that mimics a consecutive chemical reaction is used as a model for the illustration of the two ideas. Both types of correlation matrices, variable-variable and sample-sample, are analyzed, and a very good agreement between the two is met. The proposed innovations enable one to comprehend the complexity of the data to be analyzed by 2D spectroscopy and thus to avoid the risks of over-interpretation, liable to occur whenever improper caution about the number of co-existing species in the system is taken.

Artifacts↗

PubMed2006

Temperature-dependent structural changes in hydrogen bonds in microcrystalline cellulose studied by infrared and near-infrared spectroscopy with perturbation-correlation moving-window two-dimensional correlation analysis.

Temperature-dependent structural changes in hydrogen bonds (H-bonds) in microcrystalline cellulose (MCC) were investigated by infrared (IR) and near-infrared (NIR) spectroscopy. The O-H stretching fundamentals and their first overtone bands were employed to explore the structural changes. In order to analyze the overlapping OH bands due to various H-bonds, perturbation-correlation moving-window two-dimensional (PCMW2D) correlation spectroscopy was applied to the IR and NIR data. Typical spectral variation temperatures were visualized by the PCMW2D correlation analysis. Structural changes in the strong H-bonds in MCC gradually occur in the temperature region of 25-130 degrees C, and they become greater above 130 degrees C. Both OH groups with H-bonds of intermediate strength and very weak H-bonds arise from the structural change of strong H-bonds in the temperature region of 40-90 degrees C, whereas the appearance of the latter OH groups with very weak H-bonds gradually becomes dominant above 90 degrees C. It is revealed from the present study that the glass transition at 184 degrees C induces the changes in the H-bonds in the Ibeta and the O3-H3...O5 intrachain H-bonds. Band assignments for the O-H stretching first overtone vibration region are proposed based on the results of the PCMW2D correlation analyses.

Algorithms↗

PubMed2005

Accuracy and dynamic range of spatial image correlation and cross-correlation spectroscopy.

We present a comprehensive study of the accuracy and dynamic range of spatial image correlation spectroscopy (ICS) and image cross-correlation spectroscopy (ICCS). We use simulations to model laser scanning microscopy imaging of static subdiffraction limit fluorescent proteins or protein clusters in a cell membrane. The simulation programs allow us to control the spatial imaging sampling variables and the particle population densities and interactions and introduce and vary background and counting noise typical of what is encountered in digital optical microscopy. We systematically calculate how the accuracy of both image correlation methods depends on practical experimental collection parameters and characteristics of the sample. The results of this study provide a guide to appropriately plan spatial image correlation measurements on proteins in biological membranes in real cells. The data presented map regimes where the spatial ICS and ICCS provide accurate results as well as clearly showing the conditions where they systematically deviate from acceptable accuracy. Finally, we compare the simulated data with standard confocal microscopy using live CHO cells expressing the epidermal growth factor receptor fused with green fluorescent protein (GFP/EGFR) to obtain typical values for the experimental variables that were investigated in our study. We used our simulation results to estimate a relative precision of 20% for the ICS measured receptor density of 64 microm(-2) within a 121 x 98 pixel subregion of a single cell.

Algorithms↗

PubMed2005

Enhancing the sensitivity of fluorescence correlation spectroscopy by using time-correlated single photon counting.

Fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation spectroscopy (FCCS) are methods that extract information about a sample from the influence of thermodynamic equilibrium fluctuations on the fluorescence intensity. This method allows dynamic information to be obtained from steady state equilibrium measurements and its popularity has dramatically increased in the last 10 years due to the development of high sensitivity detectors and its combination with confocal microscopy. Using time-correlated single-photon counting (TCSPC) detection and pulsed excitation, information over the duration of the excited state can be extracted and incorporated in the analysis. In this short review, we discuss new methodologies that have recently emerged which incorporated fluorescence lifetime information or TCSPC data in the FCS and FCCS analysis. Time-gated FCS discriminates between which photons are to be incorporated in the analysis dependent upon their arrival time after excitation. This allows for accurate FCS measurements in the presence of fluorescent background, determination of sample homogeneity, and the ability to distinguish between static and dynamic heterogeneities. A similar method, time-resolved FCS can be used to resolve the individual correlation functions from multiple fluorophores through the different fluorescence lifetimes. Pulsed interleaved excitation (PIE) encodes the excitation source into the TCSPC data. PIE can be used to perform dual-channel FCCS with a single detector and allows elimination of spectral cross-talk with dual-channel detection. For samples that undergo fluorescence resonance energy transfer (FRET), quantitative FCCS measurements can be performed in spite of the FRET and the static FRET efficiency can be determined.

Algorithms↗

PubMed2004

[Increased expression of heparanase mRNA is correlated with metastasis of gastric carcinoma and is probably correlated with c-met protein].

OBJECTIVE: To explore the expression of human heparanase mRNA and its relationship with the clinicopathological characteristics and angiogenesis and its possible mechanism in gastric carcinomas. METHODS: Expression of heparanase mRNA in gastric cancerous tissues and its corresponding adjacent tissues were detected by RT-PCR in forty-seven patients. Expression of c-met protein and microvessel density (MVD) were examined by immunohistochemcal staining. RESULTS: Expression of heparanse mRNA was significantly higher in gastric cancerous tissues than in its adjacent tissues (74.5% vs. 19.1%, P < 0.01). MVD was significantly higher in heparanase positive group than its counterpart (51 +/- 15 vs. 31 +/- 10, P < 0.01). Expression of heparanase mRNA was correlated with expression of c-met (r = 0.714, P < 0.01). The positive rate of heparanse expression in gastric carcinomas were correlated with tumor diameter, invasive depth, regional lymph nodes metastasis and TNM stage, whereas there were no relation with gender, age, tumor differentiation and remote metastasis of the patient. CONCLUSION: Increased heparanase expression contributes to metastasis and angiogenesis in gastric cancer. Heparanase mRNA expression correlates with poor clinicopathologic characteristics in its prognosis. C-met is correlated with heparanase expression.

Adult↗

PubMed1989

[Clinical methods for evaluating infarct size and its anatomic correlations. A study conducted with 193 cases. II. Evaluation of infarct size by determining maximal creatine phosphokinase in serum. Enzimatico-anatomic correlations].

AIMS: To compare the infarct size calculated by the peak serum CK method with the anatomic infarct size in a population dying of acute myocardial infarction. CONCEPT AND PLACE OF THE STUDY: To use the method of peak serum CK in the assessment of infarct size, calculated by a method developed by the authors, in a population dying of acute myocardial infarction in a coronary care unit. METHODS: 193 patients who successively died with acute myocardial infarction entered the study. After establishing the exclusion criteria the anatomical infarct size was measured using the method developed by the authors of myocardial slices after fixation of the heart and by the peak CK method. The two methods were correlated using linear regression curves. RESULTS AND CONCLUSIONS: A global correlation between the two methods was found although wide scattered values were found. After dividing the population in several subgroups, the analysis showed that survival below 48 hours, death in left ventricular failure, inferior infarcts and reinfarction influenced negatively this correlation. The anatomical method showed its value for this kind of evaluation having always in mind its known limitations. The enzyme method looked less discriminating as peak CK, obtained by 12 h sampling will seldom reflect the peaks of CK liberation curve. As the study was applied to a population of patients dying of acute myocardial infarction its results cannot be applied without caution to a population of survivors. We anticipate that in such a population peak CK will have a better correlation with real CK peaks even with 12 hours sampling and therefore reflecting more accurately infarct size.

Autopsy↗

PubMed1998

A study of protein side-chain dynamics from new 2H auto-correlation and 13C cross-correlation NMR experiments: application to the N-terminal SH3 domain from drk.

Two new NMR experiments are presented for measuring side-chain dynamics in proteins. The first method, requiring 15N, 13C, approximately 50% 2H-labeled protein, measures 2H T1 and T1p spin relaxation times at side-chain positions. A second experiment permits the straightforward measurement of 13C-1H dipole-dipole cross-correlation relaxation rates at 13C beta positions in 15N, 13C-labeled molecules. An excellent correlation is observed between order parameters, describing the amplitude of motion at these sites, obtained on the basis of 2H relaxation and dipole-dipole cross-correlation relaxation rates. Together these experiments provide a powerful approach for selecting appropriate motional models. The methods are applied to study the side-chain motional properties of the N-terminal SH3 domain from the signaling protein drk.

Animals↗

PubMed2000

2J,(3)J-HMBC: A new long-range heteronuclear shift correlation technique capable of differentiating (2)J(CH) from (3)J(CH) correlations to protonated carbons

The development of a series of new, accordion-optimized long-range heteronuclear shift correlation techniques has been reported. A further derivative of the constant time variable delay introduced in the IMPEACH-MBC experiment, a STAR (Selectively Tailored Accordion F(1) Refocusing) operator is described in the present report. Incorporation of the STAR operator with the capability of user-selected homonuclear modulation scaling as in the CIGAR-HMBC experiment, into a long-range heteronuclear shift correlation pulse sequence, (2)J,(3)J-HMBC, affords for the first time in a proton-detected experiment the means of unequivocally differentiating two-bond ((2)J(CH)) from three-bond ((3)J(CH)) long-range correlations to protonated carbons. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Correlator beware: correlation has limited selectivity for fMRI data analysis.

Groups of time-courses created from fMRI data by the frequently used correlation analysis are often highly heterogeneous. This heterogeneity is due to the limited selectivity of correlation when trying to match brain time-courses to an externally imposed activation paradigm. Thus, this process unnecessarily generates many type I errors (false positives). Furthermore, as a consequence of the heterogeneity, time-courses identified and grouped by correlation may in fact describe different activations. After demonstrating this inadequacy, we give one particular approach to partition such a heterogeneous group into internally more homogeneous subgroups, using Kendall's coefficient of concordance W, and show its applicability and application to both simulated and in vivo data. Such group partition and "purification" will help subsequent inferential methods to deal more efficiently with false positives.

Algorithms↗

PubMedDate not supplied

Cyclin D1 overexpression in invasive breast cancers: correlation with cyclin-dependent kinase 4 and oestrogen receptor overexpression, and lack of correlation with mitotic activity.

BACKGROUND: Cyclin D1 (CCND1) and its catalytic partner cyclin-dependent kinase 4 (cdk4) are known to play important roles in the G1/S check point of the cell cycle, and CCND1 overexpression has been reported to correlate with progression and prognosis of breast cancers. Oestrogen receptor (ER) levels determine the proliferative response to oestrogen by regulating binding. It has been postulated that CCNDI and cdk4 exert effects on mammary carcinogenesis in co-operation with ER. PATIENTS AND METHODS: CCND1 and cdk4 overexpression in 117 breast cancer cases with long-term follow-up were investigated by means of immunohistochemistry and differential polymerase chain reaction (PCR), using formalin-fixed and paraffin-embedded samples, and compared with ER status and mitotic indices. Additional Western blotting and reverse transcription (RT)/PCR/Southern blot hybridization were performed for 4 breast cancer cell lines and 15 fresh-frozen breast cancer samples to confirm CCND1 and cdk4 data. RESULTS: Immunohistochemically 27 cases were CCND1-positive (23.0%), and CCND1 amplification was evident in 21 (21/86; 24.4%). The two methods in combination demonstrated 37 cases (31.6%) to be positive for CCND1 overexpression. Western blotting revealed 60% of samples of fresh tissue to overexpress CCND1, corresponding well with the results of RT-PCR. There was thus a strong discrepancy between results for paraffin block and fresh samples, probably because of the short life of CCND1. In the case of cdk4, the respective percentages for positive cases were 54.7% and 73%. CCND1 and cdk4 overexpression (P < 0.0001), and CCND1 and ER positivity (P = 0.0128) correlated. In addition, samples overexpressing CCND1, cdk4 and ER tended to have slightly lower proliferative activity than samples where these were absent. However, no association with clinicopathological parameters was evident. cdk4 overexpression had no linkage with ER status or clinicopathological status. Neither CCND1 nor cdk4 expression affected prognosis. CONCLUSION: CCND1 overexpression does not correlate with cancer progression or prognosis or with mitotic activity. The results may suggest that an excess accumulation of CCND1 in breast cancer cells tends to suppress entry into the S phase of the cell cycle.

Blotting, Western↗

PubMed1988

A simple method for determination of rotational correlation times and separation of rotational and polarity effects from EPR spectra of spin-labeled biomolecules in a wide correlation time range.

A method using nitroxide radical spin labels for determining both the isotropic rotational correlation time tau R and the environmental polarity of the label is described. By means of a least square fitting method, the values of an effective hyperfine tensor A' and of an effective g value tensor g' of randomly oriented spin labels are determined from X-band EPR spectra on the basis of an effective time-independent Hamiltonian. The traces of the tensors deliver the information about the environmental polarity of the label and are not dependent on the rotational correlation time tau R. A new averaging parameter S (tau R), calculated on the basis of the principal values of the tensor A', permits the evaluation of the rotational correlation time tau R in a very wide time range between 10(-10) and 10(-6) s. An application of this method to spin-labeled methemoglobin over a large temperature range and in environments of different polarity is discussed.

Electron Spin Resonance Spectroscopy↗

PubMed1995

Correlation of survival with quantitative tissue staining of prostate specific acid phosphatase in patients with prostate carcinoma by using microscopic image analysis: a preliminary report of correlative studies on RTOG protocols 75-06, 77-06, and 83-07.

PURPOSE: We have previously shown that the intensity (graded semiquantitatively as 1-4+) of tissue prostate-specific acid phosphatase (PSAP) staining determined immunocytochemically in a cohort of prostate carcinoma patients from Radiation Therapy Oncology Group Protocols (RTOG) protocols 75-06 and 77-06 correlated with survival. The extent of this staining was heterogeneous and was estimated. The extent of staining was not found to be significantly associated with survival. We undertook the present quantitative study to see if the improved precision and reliability of measurement of the intensity and extent of prostate specific acid phosphatase staining would confirm and extend our previous observations. METHODS AND MATERIALS: Patient cohorts representative of the entire group were obtained from RTOG 75-06 plus 77-06 and 83-07. The RTOG 77-06 plus 75-06 patients (No-Hormone population) did not receive preradiation hormonal therapy. RTOG 83-07 patients (Prehormone population) received one of two types of preradiation chemical androgen ablation. In this study, histologic slides of tumors were immunocytochemically stained for PSAP by the peroxidase-antiperoxidase (PAP) technique using diaminobenezidene (DAB) as a substrate and hematoxylin as a nuclear counterstain. The intensity and extent of immunocytochemical PSAP staining (IPSAP stain) was quantified using our dual wavelength and batch mode image process technique. RESULTS: Our study of 151 cases confirmed that overall survival of patients in both populations was positively correlated with the intensity and extent of IPSAP stain. Results of the two studies were similar. The statistical significance of the relationship of both extent and intensity was greater in the cohort from protocol 83-07, which was the patient group receiving pretreatment with hormones. In a Cox multiple regression analysis including clinical stage, Gleason and M. D. Anderson grades, and the cohort of patients (Prehormone or No-Hormone group) as covariables, both the intensity and extent of the IPSAP stain significantly correlated with survival along with M. D. Anderson grade of the tumor. CONCLUSION: Quantitative image analysis of the IPSAP stain predicts survival in patients treated with external beam radiotherapy with and without prior hormonal therapy.

Acid Phosphatase↗

PubMed2006

Correlates of depression in type 2 diabetic elderly patients: a correlational study.

OBJECTIVES: This aim of this study was to investigate depression and related factors in elderly patients (65 years) with type 2 diabetics. METHODS: The study utilized a descriptive-correlational design. Convenience sampling was applied to enroll 156 subjects, aged >or= 65 years from diabetic outpatient clinics at three hospitals in Kaohsiung. This study applied the Personal Resource Questionnaire 2000 (PRQ 2000), Taiwan Geriatric Depression Scale (TGDS), and a form for demographic data. RESULTS: (1) The mean index score for depression level was 26, indicating that study subjects had a low level of depression. The social support index score was 76. (2) Significant differences in TGDS scores existed for diabetes duration, diabetes complications, and treatment type. (3) Social support and regular exercise were significantly and negatively correlated with depression. (4) Social support and diabetes complications were significant correlates of depression and accounted for 25.9% of variance in depression. CONCLUSION: Analytical results may assist nurses in understanding depression and related factors for diabetic patients aged >or= 65. Therefore, this study could form a basis for caring older people with diabetes, and provide a reference for further research.

Aged↗

PubMed2006

Study on temperature-dependent changes in hydrogen bonds in cellulose Ibeta by infrared spectroscopy with perturbation-correlation moving-window two-dimensional correlation spectroscopy.

Infrared (IR) spectra were measured for cellulose Ibeta prepared from the mantle of Halocynthia roretzi over a temperature range of 30-260 degrees C to explore the temperature-dependent changes in hydrogen bonds (H-bonds) in the crystal. Structural changes at the phase transition temperature of 220 degrees C are elucidated at the functional group level by perturbation-correlation moving-window two-dimensional (PCMW2D) correlation spectroscopy. The PCMW2D correlation spectra show that the intensities of bands arising from O3-H3...O5 and O2-H2...O6 intrachain H-bonds dramatically decrease at 220 degrees C, whereas the intensity changes of bands due to interchain H-bonds are not observed adequately. These results suggest that the phase transition is induced by the dissociation of the O3-H3...O5 and O2-H2...O6 intrachain H-bonds. However, the interchain H-bonds are not so much responsible for the transition directly.

Carbohydrate Conformation↗

PubMed2006

Weak pairwise correlations imply strongly correlated network states in a neural population.

Biological networks have so many possible states that exhaustive sampling is impossible. Successful analysis thus depends on simplifying hypotheses, but experiments on many systems hint that complicated, higher-order interactions among large groups of elements have an important role. Here we show, in the vertebrate retina, that weak correlations between pairs of neurons coexist with strongly collective behaviour in the responses of ten or more neurons. We find that this collective behaviour is described quantitatively by models that capture the observed pairwise correlations but assume no higher-order interactions. These maximum entropy models are equivalent to Ising models, and predict that larger networks are completely dominated by correlation effects. This suggests that the neural code has associative or error-correcting properties, and we provide preliminary evidence for such behaviour. As a first test for the generality of these ideas, we show that similar results are obtained from networks of cultured cortical neurons.

Action Potentials↗

PubMed2006

The importance of including local correlation times in the calculation of inter-proton distances from NMR measurements: ignoring local correlation times leads to significant errors in the conformational analysis of the Glc alpha1-2Glc alpha linkage by NMR spectroscopy.

The experimental determination of oligosaccharide conformations has traditionally used cross-linkage 1H-1H NOE/ROEs. As relatively few NOEs are observed, to provide sufficient conformational constraints this method relies on: accurate quantification of NOE intensities (positive constraints); analysis of absent NOEs (negative constraints); and hence calculation of inter-proton distances using the two-spin approximation. We have compared the results obtained by using 1H 2D NOESY, ROESY and T-ROESY experiments at 500 and 700 MHz to determine the conformation of the terminal Glc alpha1-2Glc alpha linkage in a dodecasaccharide and a related tetrasaccharide. For the tetrasaccharide, the NOESY and ROESY spectra produced the same qualitative pattern of linkage cross-peaks but the quantitative pattern, the relative peak intensities, was different. For the dodecasaccharide, the NOESY and ROESY spectra at 500 MHz produced a different qualitative pattern of linkage cross-peaks, with fewer peaks in the NOESY spectrum. At 700 MHz, the NOESY and ROESY spectra of the dodecasaccharide produced the same qualitative pattern of peaks, but again the relative peak intensities were different. These differences are due to very significant differences in the local correlation times for different proton pairs across this glycosidic linkage. The local correlation time for each proton pair was measured using the ratio of the NOESY and T-ROESY cross-relaxation rates, leaving the NOESY and ROESY as independent data sets for calculating the inter-proton distances. The inter-proton distances calculated including the effects of differences in local correlation times give much more consistent results.

Acetylglucosamine↗

PubMed2002

Immunoglobulin G3 cardiac myosin autoantibodies correlate with left ventricular dysfunction in patients with dilated cardiomyopathy: immunoglobulin G3 and clinical correlates.

BACKGROUND: Effector functions of an aberrant immune response have been implicated in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). The immunologic determinants of myocardial dysfunction, however, remain poorly understood. This study sought to determine the relation of different immunologic responses to hemodynamic dysfunction in DCM. METHODS: Immunoglobulin (Ig) G class/subclass response ELISA (enzyme-linked immunosorbent assay) against cardiac myosin heavy chain, histologic characteristics (DALLAS criteria), immunohistochemistry, plasma interleukin-4 and plasma interferon gamma (IFN-gamma) were determined in patients (n = 76) with clinically suspected myocarditis or DCM. Patients were prospectively evaluated, both clinically and hemodynamically, on admission (baseline) and at 6-month follow-up. RESULTS: Indices of hemodynamic dysfunction (by cardiac catheterization and transthoracic echocardiography) correlated significantly with an Ig subclass response. IgG3 levels correlated with left ventricular ejection fraction (P =.02), pulmonary capillary wedge pressure (P <.0001), left ventricular end-systolic volume index (P =.002), left ventricular end-diastolic volume index (P =.033), left ventricular end-diastolic pressure (P =.04), right ventricular end-diastolic pressure (P =.039), and left ventricular end-systolic dimension and left ventricular end-diastolic dimension (P <.05). Patients positive for IgG3 (predominantly male, P =.01) had depressed left ventricular ejection fraction (< or =45%, relative risk 3.0, 95% CI 1.5-5.7, P =.005) at baseline and 6 months. Mitral-septal separation at follow-up improved in patients negative for IgG3 (P =.018), and the number of patients on conventional therapy in this group declined at 6-month follow-up (P <.05). Lymphocyte counts/high-power field; CD2, CD3, CD4, and CD8 (independent of IgG class/subclass response and left ventricular dysfunction) were significantly higher in patients positive for IFN-gamma (25%). A positive IFN-gamma response was higher in patients positive for IgG3. These patients, positive for IgG3 and IFN-gamma (10%), had significantly shorter duration of clinical symptoms: 0.17 years (0.12-2.36 y) versus 1.01 years (0.49-5.35 y, P =.04). CONCLUSION: IgG3 reactivity correlated with depressed myocardial dysfunction. This may render this subclass Ig a surrogate target for therapeutic intervention in DCM. With IFN-gamma, IgG3 may reflect a more aggressive disease.

Adult↗

PubMedDate not supplied

Homocysteinemia is inversely correlated with platelet count and directly correlated with sE- and sP-selectin levels in females homozygous for C677T methylenetetrahydrofolate reductase.

Plasma homocysteine levels depend in part on the molecular nature of the methylenetetrahydrofolate reductase (MTHFR) and on blood folate intake. Little has been reported on platelet counts in the presence of hyperhomocysteinemia and MTHFR polymorphisms, with the exception of delayed platelet recovery in homozygous MTHFR C677T subjects after treatment with methotrexate for ovarian cancer. The aim of this investigation was to evaluate the possibility of a link between the platelet count and plasma homocysteine levels in different MTHFR variants in 165 female patients. Determinations of plasma homocysteine levels were by ELISA and of MTHFR polymorphisms (A1298C and C677T) were by inverse hybridization. Serum P- and E-selectin concentrations were obtained by ELISA. An inverse correlation (R=-0.88, P<0.001) was observed between blood platelet counts and plasma homocysteine levels in the women homozygous for MTHFR C677T. This correlation did not depend on pregnancy or other variables reported. Serum concentrations of sE- and sP-selectin, markers of endothelial and platelet activation, were significantly and positively correlated with homocysteine levels. These findings suggest that homocysteine affects platelet numbers in women with MTHFR C677T possibly consequent to endothelial and platelet activation.

Adolescent↗