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At least 937 records · Page 52Linked to original sources
PubMed2006

A live cell, image-based approach to understanding the enzymology and pharmacology of 2-bromopalmitate and palmitoylation.

The addition of a lipid moiety to a protein increases its hydrophobicity and subsequently its attraction to lipophilic environments like membranes. Indeed most lipid-modified proteins are localized to membranes where they associate with multiprotein signaling complexes. Acylation and prenylation are the two common categories of lipidation. The enzymology and pharmacology of prenylation are well understood but relatively very little is known about palmitoylation, the most common form of acylation. One distinguishing characteristic of palmitoylation is that it is a dynamic modification. To understand more about how palmitoylation is regulated, we fused palmitoylation substrates to fluorescent proteins and reported their subcellular distribution and trafficking. We used automated high-throughput fluorescence microscopy and a specialized computer algorithm to image and measure the fraction of palmitoylation reporter on the plasma membrane versus the cytoplasm. Using this system we determined the residence half-life of palmitate on the dipalmitoyl substrate peptide from GAP43 as well as the EC(50) for 2-bromopalmitate, a common inhibitor of palmitoylation.

Amino Acid Motifs↗
PubMed2003

Use of sibutramine to treat obesity.

Medications are useful adjuncts to diet and exercise and may help patients lose weight and maintain significant weight loss (5%-10% from baseline). Pharmacologic approaches are indicated in those patients who have had prior weight-loss attempts, who have a body mass index greater than or equal to 30 kg/m2 or greater than or equal to 27 kg/m2 with comorbidity, and who are motivated and ready to undertake dietary and physical activity changes. This article provides a treatment algorithm to help physicians measure meaningful weight loss and proposes conservative blood pressure limits to guide the long-term prescription of sibutramine. Sibutramine can be a useful tool in the obesity treatment toolbox if used by knowledgeable practitioners.

Anti-Obesity Agents↗
PubMedDate not supplied

Measuring the PSF from aperture images of arbitrary shape--an algorithm.

A new algorithm for determining the point spread function (PSF) of digital imaging systems is presented. The input is an image of an aperture whose shape need not be regular. The aperture shape is refined to an effective sub-pixel resolution and the PSF of the system is determined by de-convolution, assuming uniform illumination and a step function edge. The method has been tested on theoretical aperture images of varying shape and PSF, with and without noise. Depending on the degree of noise, a known PSF can be recovered to an accuracy of between 0.2 and 0.8%. Some typical results are given for a Gatan Image Filter with a 794 YAG multiscan camera on a Philips EM 430 transmission electron microscope at 200 and 300 kV. An example of a de-convoluted convergent beam electron diffraction pattern is included. The algorithm tolerates a small amount of de-focus.

Journal Article↗
PubMedDate not supplied

Spectroscopy of atomic chains with tunneling microscopy.

Recently, it has been possible to create metallic chains down to seven-atom long. This has two implications. Experimentally it is necessary to have algorithms that allow converting measured data into microscopic information as, for example, processing a current-voltage curve to obtain electronic density of states (DOS). From a theoretical standpoint, we have a new framework to test extant theories and to further develop them. With this in mind, we present a new theoretical solution to the problem of mapping scanning tunneling microscopy current-voltage curves into DOS-energy curves. Our model is based on a self-consistent solution to the quantum problem of electrons in the presence of an array of attractive centers. The problem, being simpler than its three-dimensional counterparts is solved exactly for DOS and for the current-voltage curves. The main results are that the current-voltage peaks at the position of the energies of the electron in the chain and, when an impurity is present in the chain, its chemical information can be extracted from the value of analytical curves.

Journal Article↗
PubMed1997

Using prior knowledge of human anatomy to constrain MR image acquisition and reconstruction: half k-space and full k-space techniques.

In this note, we demonstrate how to utilize prior knowledge of human cranial anatomy to constrain full k-space and half k-space acquisition and reconstruction of 128 times 128 images. We used a database of magnetic resonance head images to derive new basis functions which represent the most important features of the head. the "training" images were also used to derive formulas for reconstructing head images from a subset of the usual 128 phase-encoded signals and to determine the optimal k-space locations of those signal measurements. We used this algorithm, called Feature-Recognizing MRI, to reconstruct 128 times 128 head images from 50-60% of the signals filling the full k-space. Furthermore, we combined the algorithm with a conventional half k-space technique to create 128 times 128 images from only 60% of the 80 signals required by the usual unconstrained half k-space imaging. Thus, the prior knowledge represented by the image database, together with a half k-space technique, made it possible to construct accurate magnetic resonance images from only 30-40% of the complete set of 128 signals. In other words, a database of head images was used to devise a 1/3 k-space method for imaging the head.

Adult↗
PubMed1997

Left ventricular hypertrophy in hypertensive patients is associated with abnormal rate adaptation of QT interval.

OBJECTIVES: This study sought to examine whether the responses of the QT interval to changes in the heart rate were altered in left ventricular hypertrophy (LVH). BACKGROUND: The QT interval has been shown to have a delayed adaptation to sudden changes in heart rate in normal subjects. Abnormalities in the adaptation of the QT interval to changes in the RR interval may facilitate the development of ventricular arrhythmias. METHODS: Consecutive newly diagnosed hypertensive subjects, not taking any medications, were age and gender matched for LVH (n = 21) versus on LVH (n = 16). QT interval dynamics were analyzed under visual control using a validated algorithm with automatic QT measurements at the end of the T wave. A computerized Holter system was developed to study the QT interval response to changes in the RR interval. The adaptive response of the QT interval was measured as the ratio of the slope from 10% to 90% of the QT change relative to the RR interval change (dQT/dRR10-90). Steady state adaptation was also studied as the percent shortening and lengthening of the QT interval during acceleration and deceleration of heart rate. RESULTS: The adaptive response of the QT interval measured as dQT/dRR10-90 was increased in the LVH group compared with that in the control subjects during both acceleration (0.33 +/- 0.06 vs. 0.18 +/- 0.02, p = 0.02) and deceleration phases (0.23 +/- 0.04 vs. 0.16 +/- 0.02, p = 0.03). In the LVH group, the percent lengthening of the QT interval was greater (7.6 +/- 0.7 vs. 5.1 +/- 0.2, p = 0.03), whereas the percent shortening was not significantly different (5.71 +/- 0.5 vs. 4.6 +/- 0.3, p = 0.43), than that in control subjects. CONCLUSIONS: The QT interval response to changes in the RR interval is rapid and exaggerated in LVH. These abnormalities of the QT interval response demonstrate that there are altered repolarization dynamics in patients with LVH that may make them vulnerable to serious ventricular arrhythmias.

Adaptation, Physiological↗
PubMed1998

Detection of high intensity transient signals (HITS): how and why?

HITS (high intensity transient signals) in transcranial Doppler recordings reflect either microemboli, both gaseous and solid, or artefacts. Various frequencies in number of microembolic signals (MES) have been reported in the same clinical condition. A possible explanation for these discrepancies may be different device settings and algorithms for embolus detection. For reproducibility of data, we suggest that studies on MES report the following parameters: (1) Ultrasound device; (2) transducer type; (3) insonated artery; (4) insonation depth; (5) algorithms for signal intensity measurement; (6) scale settings; (7) detection threshold; (8) axial extension of sample volume; (9) fast Fourier transform (FFT) size (number of points used); (10) FFT length (time); (11) FFT overlap; (12) transmitted ultrasound frequency; (13) high pass filter settings; and (14) recording time. No current system of automatic embolus detection has the full sensitivity and specificity required for clinical use. Therefore, each of the signals detected by these devices needs to be checked and verified by an experienced investigator. MES will help to identify the site and activity of the embolizing lesion. Microembolus detection might reduce the observation time and the number of patients needed to perform interventional trials. First, however, MES needs to be validated as a meaningful prognostic parameter. Microemboli originating from prosthetic cardiac valves are mainly gaseous. Therefore, they cannot serve as an indicator of the valves thromboembolic activity or the patient's stroke risk.

Carotid Stenosis↗
PubMed2004

A method of obtaining starting values of k(in) and k(out) for the indirect response models.

A method based on the multivariate technique known as principal component analysis is proposed to obtain starting values for the rate constants of indirect response models. The method is not iterative and only requires standard deviation calculations for two quantities, which are simple functions of the measured pharmacodynamic response. An algorithm is provided which can be implemented in a spreadsheet. The methodology is justified theoretically herein, nevertheless, two examples are provided to illustrate the method and demonstrate its viability.

Algorithms↗
PubMed2002

Regulation of gene expression by melatonin: a microarray survey of the rat retina.

The pineal secretory product melatonin is synthesized by pinealocytes and retinal photoreceptors on a cyclic rhythm, with highest levels occurring at night. Our previous work has demonstrated that melatonin treatment increases the sensitivity of the rat retina to light-induced photoreceptor cell death. This raises the possibility that inappropriate exposure of photoreceptors to melatonin may result in visual impairment, caused by a loss of retinal photoreceptors. We hypothesize that retinal genes whose expression levels are altered in response to melatonin may be involved in processes that contribute to light-induced photoreceptor cell death. To identify retinal genes that are up- or down-regulated in response to melatonin receptor binding, rats were treated with or without melatonin, and the RNA from the neural retinas and retinal pigment epithelium (RPE) were analyzed for differential gene expression by hybridization of labeled cRNA probes to an Affymetrix rat genome microarray set. GeneChip algorithms were applied to measured hybridization intensities of compared samples and showed that in the neural retina, six genes were up-regulated, and eight were down-regulated. In the RPE, 15 genes were up-regulated, and two genes were down-regulated. The protein products of these specific genes are potentially involved in the molecular mechanism of melatonin action in the retina, and may play a role in the effect of melatonin on light-induced photoreceptor cell death. Identification of these candidate genes and their response to melatonin administration may provide a foundation for further studies on gene regulation by melatonin, the function of melatonin in the retina, and the role of circadian signaling in inherited and environmentally induced photoreceptor degenerations.

Animals↗
PubMed2005

Global estimate of aerosol direct radiative forcing from satellite measurements.

Atmospheric aerosols cause scattering and absorption of incoming solar radiation. Additional anthropogenic aerosols released into the atmosphere thus exert a direct radiative forcing on the climate system. The degree of present-day aerosol forcing is estimated from global models that incorporate a representation of the aerosol cycles. Although the models are compared and validated against observations, these estimates remain uncertain. Previous satellite measurements of the direct effect of aerosols contained limited information about aerosol type, and were confined to oceans only. Here we use state-of-the-art satellite-based measurements of aerosols and surface wind speed to estimate the clear-sky direct radiative forcing for 2002, incorporating measurements over land and ocean. We use a Monte Carlo approach to account for uncertainties in aerosol measurements and in the algorithm used. Probability density functions obtained for the direct radiative forcing at the top of the atmosphere give a clear-sky, global, annual average of -1.9 W m(-2) with standard deviation, +/- 0.3 W m(-2). These results suggest that present-day direct radiative forcing is stronger than present model estimates, implying future atmospheric warming greater than is presently predicted, as aerosol emissions continue to decline.

Aerosols↗
PubMed2004

[Performance of anesthesia systems in the future, O(2) delivery and O(2) measurement as example].

Closed loops will help to simplify the operation of anesthesia devices in the future. The technical prerequisites for the closed loop controlled delivery of oxygen are a electronically controlled dosage system, a fast and redundant O (2) measurement and the right algorithms. Benefits from this closed loop control are a steady quality of oxygenation, the O (2) uptake and consumption data.

Anesthesia↗
PubMed2006

[Invasive airway management].

Invasive airway management techniques are the bottom line of most difficult airway management algorithms when less invasive measures (e.g. endotracheal intubation, bag-valve-mask ventilation, or supraglottic airways) have failed. Various devices for transtracheal jet ventilation in children are available, while cricothyrotomy is the gold standard for establishing an invasive airway in adults. Percutaneous tracheostomy could become an alternative to cricothyrotomy if applied by experienced physicians, however, clear scientific evidence to advocate percutaneous tracheostomy in airway emergencies is still pending.

Anesthesia↗
PubMed1987

[Classification of spot-shaped lung changes by texture analysis].

Classification of opacities in pneumoconiosis was accomplished by textural analysis in digitised chest x-rays. A good discrimination was achieved by a set of 10 parameters. These texture measures were computed by algorithms for edge detection, local extremes, difference statistics, the co-occurrence matrix and the power spectrum. The classes of the training set were classified correctly at 99%. A test set comprising additional classes that were not contained in the training set, was classified at 82%.

Algorithms↗
PubMed2001

Extracting information from cDNA arrays.

High-density DNA arrays allow measurements of gene expression levels (messenger RNA abundance) for thousands of genes simultaneously. We analyze arrays with spotted cDNA used in monitoring of expression profiles. A dilution series of a mouse liver probe is deployed to quantify the reproducibility of expression measurements. Saturation effects limit the accessible signal range at high intensities. Additive noise and outshining from neighboring spots dominate at low intensities. For repeated measurements on the same filter and filter-to-filter comparisons correlation coefficients of 0.98 are found. Next we consider the clustering of gene expression time series from stimulated human fibroblasts which aims at finding co-regulated genes. We analyze how preprocessing, the distance measure, and the clustering algorithm affect the resulting clusters. Finally we discuss algorithms for the identification of transcription factor binding sites from clusters of co-regulated genes. (c) 2001 American Institute of Physics.

Journal Article↗
PubMed2006

An innovative approach to teaching resuscitation skills.

We report the impact of a monthly educational exercise for residents that emphasized practical skills and equipment usage rather than knowledge of advanced cardiac life support (ACLS) protocols. Residents were divided into groups of approximately four that rotated through three stations. Each station included several objectives, most of which related to specific types of equipment. The exercise was held six times from July 2003 to June of 2004. Sixty-seven residents participated and completed a questionnaire prior to and following the exercise. The questionnaire elicited comfort level with basic tasks including using an automated external defibrillator (AED), attaching leads and paddles to read a cardiac rhythm, delivering unsynchronized shocks with monophasic and biphasic defibrillators and implementing the pacing function on a defibrillator. There were significant differences in the pre- and post-answers to each question. The largest difference was found in the question asking how comfortable participants were delivering unsynchronized shocks with a defibrillator. Importantly, responses for the question 'How comfortable are you being a code leader?' showed significant improvement. Simple skills such as attaching tubing to the oxygen tank, turning on the defibrillator and entering appropriate charge, or positioning paddles and monitor leads properly often caused significant difficulty. Cardiopulmonary arrests tend to generate anxiety among house staff, despite certification in ACLS and adequate knowledge of protocols. Exercises, such as the one presented here, will reduce anxiety by specifically addressing this skill. We conclude that residents benefit from additional teaching and practice in actual performance of basic skills used during cardiac arrests. Furthermore, our data demonstrate that comfort levels among house officers increase when they are given the opportunity to practice these skills.

Advanced Cardiac Life Support↗
PubMed2001

Reconstruction of conductivity changes due to ventilation and perfusion from EIT data collected on a rectangular electrode array.

In this paper we demonstrate that conductivity changes caused by ventilation and perfusion in a human subject can be reconstructed from electrical impedance tomography data collected on a rectangular array of electrodes placed on a subject's chest. Currents are applied on the electrodes and the resulting voltages on the electrodes are measured. A 3D reconstruction algorithm is used to reconstruct the conductivity distribution in the region beneath the array. Time traces of the reconstructed conductivity distribution demonstrate the detected changes in conductivity due to ventilation and perfusion.

Algorithms↗
PubMed1988

Discriminant analysis of promoter regions in Escherichia coli sequences.

We have previously developed a general method based on the statistical technique of discriminant analysis to predict splice junctions in eukaryotic mRNA sequences [Nakata, K., Kanehisa, M. and DeLisi, C. (1985) Nucleic Acids Res., 13, 5327-5340]. In order to evaluate further applicability of this method, we now analyze the promoter region of Escherichia coli sequences. The attributes used for discrimination include the accuracy of consensus sequence patterns measured by the perceptron algorithm, the thermal stability map, the base composition and the Calladine-Dickerson rules for helical twist angle, roll angle, torsion angle and propeller twist angle. When applied to selected E. coli sequences in the GenBank database, the method correctly identifies 75% of the true promoter regions.

Algorithms↗