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PubMed2006

Knowledge-based proteome profiling: considering identified proteins to evaluate separation efficiency by 2-D PAGE.

Proteome profiling techniques rely on the separation of proteins or peptides and their subsequent quantification. The reliability of this technique is still limited because a proteome profiling result does not necessarily represent the true protein composition of the analysed sample, thus seriously hampering proper data interpretation. Many experimentally observed proteome alterations are biologically not significant. It was the aim of this study to use the knowledge of the biological context of proteins in order to establish optimised proteome profiling protocols. While 2-D spot patterns of total cell protein fractions were found to poorly represent the true protein composition, purified subcellular protein fractions were found to better represent the protein composition of the analysed sample. The application of a standardised protocol to different kinds of cells revealed several striking observations. Firstly, the protein composition of cultured cells of various origins is very similar. Secondly, proteome alterations observed with the described protocols do make sense from a biologic point of view and may thus be considered as truly representative for the analysed samples. Thirdly, primary white blood cells isolated from different donors were found to show minor, but reproducible and significant individual differences. We designate the consideration of known properties of identified proteins in proteome profiles as a knowledge-based approach. The present data suggest that this approach may tremendously help to improve the applied techniques and assess the results. We demonstrate that the fulfilment of well-defined criteria of proteome profiles eventually results in reliable and biologically relevant data.

Amino Acid Sequence↗
PubMed1991

[High pressure extraction of marjoram. 1. Sensory characterization of marjoram oleoresin by profile analysis].

A flavour profile analysis has been developed for the evaluation of carbon dioxide extracts of marjoram. On the basis of the commercial quality of various proveniences of marjoram a first flavour profile was established. Components which decisively influence the flavour were examined for the determination of relevance factors. The taste profile is the basis for the calculation of the quality coefficient as measure of the sensory quality. The expert profile as a theoretical model is based on optimum intensities of individual taste components. Differences from the expert profile are considered by corrected intensities and lead to a decrease of the quality coefficient. The method used for the development of a high pressure extraction technology is quite suitable for the characterization of marjoram extracts as well as for the evaluation of commercial marjoram samples.

Carbon Dioxide↗
PubMed1986

Platelet population profiles: significance of species variation and drug-induced changes.

Platelet counts are routinely assessed from whole blood samples and recent technical advances enable the total platelet counts to be complemented by additional information which fully profiles the platelet population. In this report the platelet count, mode and mean platelet volumes and platelet profile histograms are presented for eight mammalian species. Species and strain variation in platelet profiles and the degree of volume heterogeneity are presented, and a platelet profile is presented for the marmoset which is previously unreported. The significance of these parameters and their potential importance to the toxicologist are discussed in the light of an observation of a drug-induced alteration in a platelet population profile.

Adolescent↗
PubMed2005

Micromechanics of shelf-aged and retrieved UHMWPE tibial inserts: indentation testing, oxidative profiling, and thickness effects.

Understanding the surface micromechanical properties of ultra-high-molecular-weight polyethylene (UHMWPE) may allow for improvement in its wear characteristics. Microtomed sections of two UHMWPE tibial bearings, one that had been irradiation sterilized and shelf-aged, and the other irradiation sterilized and used in a patient, were subjected to depth sensing indentation testing. The microtomed sections exhibited a white band in the subsurface region that is characteristic of oxidation, and the indentation testing, followed by FTIR analysis at the same testing locations, was performed across this region and into the bulk of the material. Indentation testing yielded data leading to hardness, modulus, and energy dissipation factor (EDF). FTIR profiling generated information about oxidation; oxidation indices were calculated by taking a ratio of peak heights at 1,716 cm(-1) (ketone) to 2,022 cm(-1) (methylene). The mechanical properties showed a strong linear correlation with oxidation index above a minimum thickness. Modulus, hardness, and EDF all increased with increasing oxidation. The appropriate thickness-to-indentation-depth ratio was determined by two methods and was found to be approximately 20:1. The mechanical properties through the oxidized region were seen to vary with depth into the sample in a profile similar to the oxidation profile. The differing aging environments of the tibial bearings are hypothesized to have had an effect on both the mechanical and oxidation profiles. The retrieved bearing exhibited a narrower oxidation profile with peaks closer to the surface, and oxidation indices of lower magnitude. The mechanical properties proved similar, with less intense and narrower readings for the retrieved sample. This research is consistent with much of the literature.

Humans↗
PubMed2003

Isomers of C(20): an energy profile II.

Semi-empirical calculations, at the PM3 level provided within the Winmopac v2.0 software package, are used to geometrically optimize and determine the absolute energies (heats of formation) of a variety of C(20) isomers that are predicted to exist in and around the bowl and cage isomers. Using the optimized Cartesian coordinates for the bowl and the cage isomers, a saddle-point calculation was performed. The output file generated, containing energy, distance, and geometry information, is then organized into a graphical format. The resulting graph, which plots the energy of the 20-atom system as a function of the distance from the geometric midpoint, is a two-dimensional energy profile. This profile illustrates an estimation of the contours on the potential energy surface, showing energy minima and maxima that are encountered as the bowl evolves into the cage structure, or vice-versa. To expand the surface into three dimensions, geometry optimizations were performed on the sets of Cartesian coordinates that correspond to energy minima in the bowl-cage profile. Based on these optimizations, eight additional isomers of C(20) have been identified and are predicted to be energetically stable. These additional isomers were subsequently subjected to saddle-point calculations in order to identify those isomers that lie adjacent to one another on the three-dimensional surface. Two isomers that are adjacent to each other will exhibit an energy profile that progresses smoothly from the potential well of each isomer up to the saddle point separating them. Consequently, these adjacent pairs of isomers establish a step-wise transformation between the bowl and the cage. This process, which extends out over the three-dimensional surface, is predicted to require less energy than that of the direct, two-dimensional transformation predicted in the bowl-cage profile.

Journal Article↗
PubMed2002

Software news and updates. Basis-set completeness profiles in two dimensions.

A two-electron basis-set completeness profile is proposed by analogy with the one-electron profile introduced by D. P. Chong (Can J Chem 1995, 73, 79). It is defined as Y(alpha, beta) = sigmam sigman (Galpha(1)Gbeta(2)/(1/r12)/ psim(1)psin(2)) (psim(1)psin(2)/r12/Galpha(1)Gp(2)) and motivated by the expression for the basis-set truncation correction that occurs in the framework of explicitly correlated methods (Galpha is a scanning Gaussian-type orbital of exponent alpha and [psim] is the orthonormalized one-electron basis under study). The two-electron basis-set profiles provide a visual assessment of the suitability of basis sets to describe electron-correlation effects. Furthermore, they provide the opportunity to assess the quality of the basis set as a whole--not only of the individual angular momentum subspaces, as is the case for the one-electron basis-set profiles. The two-electron completeness profiles of the cc-pVXZ (X = D, T, Q), aug-cc-pVTZ, cc-pCVTZ, and SVP-auxiliary basis sets for the carbon atom are presented as illustrative examples.

Journal Article↗
PubMed2001

MMPI-2 profiles of filicidal, mariticidal, and homicidal women.

The present study compared the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) clinical and content scale profiles of a group of adult women (N = 73) charged with either murder of their child (filicide) (n = 30), their partner (mariticide) (n = 19), or an unrelated adult (homicide) (n = 24). No significant differences were seen among the three groups on either the MMPI-2 clinical or content scales. Clinical inspection of the 53 valid MMPI-2 profiles (F < 110T) revealed a 6-8 mean profile for the filicidal women, a 2-6 mean profile for the mariticidal women, and a 4-8 mean profile for the homicidal women. Application of the data for criminal forensic psychological evaluations is discussed.

Adult↗
PubMed2003

Variation correction algorithm: analysis of phase suppression and thermal profile fidelity for proton resonance frequency magnetic resonance thermometry at 0.2 T.

PURPOSE: To develop and analyze the performance of the variation correction algorithm (VCA), a phase correction technique that mitigates the contribution of background phase variations by combining accurate alignment of echoes, K-space-based phase correction (as opposed to spatial polynomials), and extraction of alias-free phase difference images. MATERIALS AND METHODS: A series of echo-shifted gradient-recalled echo (GRE) images was processed with K-space alignment and phase corrected with increasing sizes of M x M masks of central K-space coefficients. The extent of background phase variation suppression due to magnet field drift was assessed. Further, a simulated thermal profile was superimposed on the same data in a related experiment. Residual errors in reconstructed simulated thermal profiles were quantitatively characterized to estimate algorithm performance. RESULTS: Using a 3 x 3 K-space mask, the VCA was able to 1) maintain the typical mean background error in a 35 x 35 pixel region of interest (ROI) at -0.1 degrees C; and 2) reconstruct, relative to the applied thermal profile, a phase-corrected profile that typically contains a 1.7 degrees C underestimation of peak temperature difference and a mean error along the 60 degrees C line of -0.8 degrees C. CONCLUSION: The results suggest that thermal profiles can be accurately reconstructed at 0.2 T using the VCA, even in the presence of over 1 ppm spatially and temporally dependent field drift over a 1-hour time frame.

Algorithms↗
PubMed2006

Cognitive profiles of individual patients with Parkinson's disease and dementia: comparison with dementia with lewy bodies and Alzheimer's disease.

We describe the pattern of cognitive profiles within a community-based sample of patients with Parkinson's disease (PD) and dementia (PDD) using cluster analyses, and compare the results with data from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Fifty patients with PDD and 39 with AD from Stavanger, Norway, and 62 patients with DLB from San Diego, CA, USA were diagnosed by either standardized clinical procedures or criteria (all PDD and all AD cases) or necropsy (all DLB cases). Four subgroups were identified: two subgroups with a subcortical cognitive profile (one with mild and one with moderate dementia severity), one subgroup with global impairment and severe dementia, and one subgroup with a cortical cognitive profile and moderate dementia. Of the patients with PDD and with DLB, 56% and 55%, respectively, had a subcortical cognitive profile, compared with only 33% of the AD patients. Conversely, 30% of the patients with PDD and 26% of those with DLB had a cortical cognitive profile, compared with 67% of the patients with AD. These findings suggest that in some patients with PDD, frontosubcortical changes are the main contributing factor to dementia, whereas in other patients, cortical and hippocampal changes are more important.

Aged↗
PubMed1988

Epididymal sperm profiles in young adult, middle-aged, and testosterone-supplemented old rats.

Both ejaculated semen and epididymal contents from an individual male contain sperm that differ in various physicochemical characteristics. An experiment is reported in which epididymides from rats 5-24 months old were subjected to density gradient centrifugation to separate gametes of different stages of maturity. The research was designed to examine typical changes in "profiles" of sperm maturity during the reproductive lifetime of rats. Also, testosterone complexed with cyclodextrin that mimics the episodic release of the endogenous hormone was used to supplement the decreased circulating titers of some of the old males. Results revealed clear ontogenetic patterns of gradually decreasing reproductive competence as measured by absolute numbers of sperm, circulating levels of testosterone, and various other physiological markers of fertility. Sperm profiles also revealed age-specific changes with a shift toward progressively more mature, perhaps senile, gametes that begins at middle age. Testosterone supplementation (400 micrograms/kg b.w./day for 30 days) failed to restore sperm numbers or other measures of physiology in the old males, but the steroid modified sperm profiles to approximate more closely the profiles characteristic of young adult males than either untreated middle-aged or old males. The data were interpreted as suggesting that epididymal sperm profiles clearly identify males of different ages, and that the aging epididymis retains its capacity to respond to manipulations that modify the endocrine milieu.

Aging↗
PubMed2004

TurboFLASH FAIR imaging with optimized inversion and imaging profiles.

Optimal implementation of pulsed arterial spin labeling (PASL) methods such as flow-sensitive alternating inversion recovery (FAIR), require the minimization of interactions between the inversion and imaging slabs. For FAIR, the inversion:imaging slice thickness ratio (STR) is usually at least 3:1 in order to fully contain the extent of the imaging slice. The resulting gap exacerbates the transit time. So far, efforts to minimize the STR have concentrated on the inversion profile. However, the imaging profile remains a limiting factor especially for rapid sequences such as turbo fast low-angle shot (TurboFLASH) which uses short pulses. This study reports the implementation of a TurboFLASH sequence with optimized inversion and imaging profiles. Slice-selection is achieved with a preparation module incorporating a pair of identical adiabatic frequency offset corrected inversion (FOCI) pulses. The optimum radiofrequency (RF) and gradient scheme for this pulse combination is described, and the relaxation characteristics of the slice-selection scheme are investigated. Phantom experiments demonstrate a reduction in the STR to approximately 1.13:1. Implementation in an animal model is described, and the benefit of the improved profile in probing the sensitivity of the flow signal to tagging geometry is demonstrated. Sensitivity to transit time effects can be minimized with this sequence, and ASL methodologies can be better explored as a result of the improved conformance with the ideal of square slice profiles.

Animals↗
PubMed1991

Fast MR cardiac profiling with two-dimensional selective pulses.

A rapid-profiling NMR pulse sequence has been designed to provide an interactive, real-time cardiac probe analogous to M-mode ultrasound. The pulse sequence employs a two-dimensional (2D) selective NMR pulse to excite a narrow (nominally 1-cm-diameter) cylinder of magnetization intersecting the heart. This procedure is followed by a readout gradient applied along the length of the cylinder, or "beam," to yield an M-mode type profile with a one-dimensional Fourier transform reconstruction. k-space techniques were used to design 2D pulses which excite cylinders characterized by either Gaussian or square radial excitation profiles. Images of phantoms acquired at 1.5 T confirm the predictions of the k-space analysis. The cylinder can be displaced interactively by modulating the rf excitation and the beam axis can be reoriented to any oblique direction by changing the relative mixing of the gradient waveforms. Flow compensation using bipolar gradient waveforms inverts the contrast of flowing blood and suppresses flow artifacts. A gated cardiac image is acquired as a reference to locate the excitation axis. A series of cardiac experiments was performed on several healthy volunteers. As the beam is moved and rotated to probe the myocardium, the profile plots resemble an M-mode echocardiogram. Unlike in M-mode echocardiography, however, the axis of interrogation is not limited to specific windows, and there is distinct flexibility of contrast. However, the temporal resolution is currently less than that achieved by ultrasound. NMR M-mode profiling provides a direct, fast method of measuring heart motion to assess cardiac function as part of an MR cardiac exam.

Fourier Analysis↗
PubMed2004

Cross-cultural adaptation of the Sensory Profile: establishing linguistic equivalency of the Hebrew version.

In the process of translating assessment tools from one language to another, researchers often run the risk of altering the intended meaning of the test items, and consequently affecting the validity of the assessment tool. In this study, the accuracy of a Hebrew translation of the Sensory Profile (Dunn, 1999) was validated. A multi-step process, based on back-translation and the bilingual method was undertaken to examine whether the Hebrew translation was linguistically equivalent to the original Sensory Profile. Quantitative and qualitative measures were used to detect and explain inconsistencies in the translation. The analysis of the back-translation revealed that the discrepancies found in a number of items stemmed from inaccurate translation or back-translation, erroneous substitution, omission, or addition of words/phrases, and from substitution of words/phrases because there was no equivalent in the Hebrew language. Of the 59 back-translated items, which were not linguistically equivalent to the original Sensory Profile items, only 12 items generated inconsistent responses by the bilingual parents. Overall, the responses of the bilingual parents to the Hebrew and the English version were inconsistent in 26 of the 125 Sensory Profile items. The coefficient alpha values in all sections of the Hebrew version (except for section N) were above.70, indicating a good overall reliability. Based on proposed criteria, results indicate that the Hebrew translation of the Sensory Profile is accurate. Inconsistencies found in a number of items may relate to connotation effect, language effect, and measurement errors.

Adult↗
PubMed2004

Morphological changes in tumour type after radiotherapy are accompanied by changes in gene expression profile but not in clinical behaviour.

The morphological features of neoplastic cells, combined with a stromal reaction, determine the presence of cancer at the microscopic level. Malignant tumours arise through a series of genetic alterations, but these do not entirely explain invasive and metastatic behaviour and correlate only weakly with morphological changes. In order to understand the relationship between the morphology of cancer tissue, gene expression, and clinical behaviour, a study of radiation-induced mucinous rectal carcinoma was performed. Short-term radiotherapy of rectal carcinoma results in an increased incidence of mucinous carcinoma. A cohort of rectal carcinomas (n = 1304), from patients who participated in a randomized radiotherapy trial, was evaluated for the presence and amount of a mucinous component. The results were compared with data from the pre-irradiation biopsies and revealed the presence of two distinct classes of mucinous carcinoma in the radiotherapy group, namely pre-existing (un-induced; n = 24) and induced mucinous carcinoma (n = 29). Clinical data, pathological parameters, and immunohistochemical data from these patients and their tumours showed that induced mucinous carcinomas were more comparable to typical adenocarcinomas than to pre-existing mucinous carcinomas. The prognosis of patients with induced mucinous carcinoma was significantly better than that of patients with pre-existing mucinous carcinomas (91.2% versus 39.3% recurrence-free interval at 2 years, p = 0.02). Gene expression profiles of the different groups of mucinous carcinomas and adenocarcinomas were analysed using Affymetrix Human Cancer Chips. Surprisingly, despite the difference in prognosis, the expression profile of radiation-induced mucinous carcinomas was very closely related to that of their un-induced counterparts. It is shown in the present study that radiation therapy of rectal cancer leads within a few days to substantial changes in both morphology and expression profile. However, the morphology of the pre-therapy biopsy predicts patient survival far better than post-therapy expression profiles. It is concluded that tumour morphology equates to expression profile, but that external factors might influence both, leading to sub-optimal prognostication.

Adenocarcinoma, Mucinous↗
PubMed2003

Spatial profiling of protein hydrophobicity: native vs. decoy structures.

A recent study of 30 soluble globular protein structures revealed a quasi-invariant called the hydrophobic ratio. This invariant, which is the ratio of the distance at which the second order hydrophobic moment vanished to the distance at which the zero order moment vanished, was found to be 0.75 +/- 0.05 for 30 protein structures. This report first describes the results of the hydrophobic profiling of 5,387 non-redundant globular protein domains of the Protein Data Bank, which yields a hydrophobic ratio of 0.71 +/- 0.08. Then, a new hydrophobic score is defined based on the hydrophobic profiling to discriminate native-like proteins from decoy structures. This is tested on three widely used decoy sets, namely the Holm and Sander decoys, Park and Levitt decoys, and Baker decoys. Since the hydrophobic moment profiling characterizes a global feature and requires reasonably good statistics, this imposes a constraint upon the size of the protein structures in order to yield relatively smooth moment profiles. We show that even subject to the limitations of protein size (both Park & Levitt and Baker sets are small protein decoys), the hydrophobic moment profiling and hydrophobic score can provide useful information that should be complementary to the information provided by force field calculations.

Algorithms↗
PubMed2005

The effect of provider-level ascertainment bias on profiling nursing homes.

Profiling health care providers for the purpose of public reporting and quality improvement has become commonplace. Recently, the Centers for Medicare and Medicaid Services (CMS) began publishing measures of quality for every Medicare/Medicaid-certified nursing home in the country. The facility-specific quality indicators (QIs) reported by CMS are based on quarterly measures from the minimum data set (MDS). However, some QIs from the MDS are potentially subject to ascertainment bias. Ascertainment bias would occur if there was variation in the way items that make up QIs are measured by nurses from each facility. This is potentially a problem for difficult-to-measure items such as pain and pressure ulcers. To assess the impact of ascertainment bias on profiling, we utilize data from a reliability study of nursing homes from six states. We develop methods for profiling providers in situations where the data consist of a response variable for each subject based on assessments from an internal rater, and, for a subset of subjects in each facility, a response variable based on assessments from an independent (external) rater. The internal assessments are potentially subject to provider-level ascertainment bias, whereas the independent assessments are considered the 'gold standard'. Our methods extend popular Bayesian approaches for profiling by using the paired observations from the subset of subjects with error-prone and error-free assessments to adjust for ascertainment bias. We apply the methods to MDS merged with the reliability data, and compare the bias-corrected profiles with those of standard approaches.

Aged↗
PubMed1994

WAIS-R subtest profile and cortical perfusion in Alzheimer's disease.

WAIS-R profiles were investigated in 28 Alzheimer's disease (AD) and 21 healthy elderly subjects. The Fuld subtest profile, previously reported to have potential as a diagnostic marker for AD, was observed in 35.7% of our AD patients and 4.8% of the controls. We compared AD patients with the Fuld profile (ADF+) to a group of patients without the profile (ADF-) with similar demographics and dementia severity and demographically matched normals using regional Cerebral Blood Flow. Both AD groups showed reduced blood flow in the parietotemporal cortex compared to normals, but the ADF+ patients had greater flow reductions than the ADF- group. Examination of WAIS-R performance indicated that the ADF+ group had lower scores than the ADF- patients on the Digit Symbol and Block Design subtests, and further, that these two subtests were associated with the parietotemporal perfusion deficit in our AD sample. Our findings do not support the use of the Fuld profile as a diagnostic marker for AD, but do provide physiological evidence for behavioral heterogeneity among AD patients based on WAIS-R subtest performance.

Aged↗
PubMed2001

An expression profile of active genes in human conjunctival epithelium.

The purpose of this study was to describe the quantitatively and qualitatively genes expressed in in vivo human conjunctival epithelium. A cDNA library was created from human conjunctival epithelial cells obtained from 38 normal eyes by brush cytology. Poly A(+)RNA isolated from these cells was used as a template for cDNA synthesis by the vector-priming method. A 3'-directed cDNA library consisting of the cDNA moiety covering the poly A(+)RNA tail through the nearest Mbo I site was constructed and transformed into Escherichia coli. Inserts in 933 randomly chosen clones were sequenced. The resulting sequences were compared to determine frequency of appearance in the library, and to establish an expression profile of genes in the conjunctival epithelium. The sequences were sent to GenBank for gene identification. The result was an expression profile of active genes reflecting their relative abundance in the conjunctival epithelial mRNA population. The expression profile of human conjunctival epithelium showed that the most abundant gene transcript in human conjunctival epithelium was that for cytokeratin 13. Altogether 102 genes were found to be very active, including beta-2 microglobulin, lipocortin I and insulin-like growth factor binding protein-3. The gene expression profile of the conjunctival epithelium reflects the unique properties and functions of this tissue. Comparison of this expression profile with that obtained from corneal epithelium discloses clear differences and helps us better understand the physiology and pathophysiology of the ocular surface in humans.

Adult↗