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At least 919 records · Page 51Linked to original sources
PubMed2006

Conceptual structure modulates anteromedial temporal involvement in processing verbally presented object properties.

Recent research has indicated that anteromedial temporal cortex (including the perirhinal cortex) may function as the endpoint of a hierarchically organized visual object-processing network providing the basis for fine-grained discrimination among objects. The present study examines whether the same system is involved in processing conceptual information when concepts, and their properties, are denoted by words. A lesion-behavior correlational study was conducted in which cortical damage in 21 brain-damaged patients was correlated with behavioral scores in a verbally presented property verification task. Results indicated that the neural correlates of conceptual processing depend on the dynamic interaction between the content of a conceptual representation and the specific demands of the task and that the role of anteromedial temporal cortex in this process is not limited to the visual input modality. The results are consistent with the claim that anteromedial temporal cortex provides the neural structure necessary for the emergence of fine-grained conceptual knowledge about objects, although the region is strongly weighted toward processing of visually based object features.

Adaptation, Physiological↗
PubMed2006

Locating mammalian transcription factor binding sites: a survey of computational and experimental techniques.

Fields such as genomics and systems biology are built on the synergism between computational and experimental techniques. This type of synergism is especially important in accomplishing goals like identifying all functional transcription factor binding sites in vertebrate genomes. Precise detection of these elements is a prerequisite to deciphering the complex regulatory networks that direct tissue specific and lineage specific patterns of gene expression. This review summarizes approaches for in silico, in vitro, and in vivo identification of transcription factor binding sites. A variety of techniques useful for localized- and high-throughput analyses are discussed here, with emphasis on aspects of data generation and verification.

Animals↗
PubMed2002

A model and experimental study of fiber orientation effects on shear wave propagation through composite laminates.

The strong elastic anisotropy of the discrete unidirectional plies in a composite laminate interacts sensitively with the polarization direction of a shear ultrasonic wave propagating in the thickness direction. The transmitted shear wave can therefore be used to detect errors in the ply orientation and stacking sequence of a laminate. The sensitivity is particularly high when the polarization directions of the shear wave transmitter and receiver are orthogonal to each other. To understand the interaction between normal-incident shear waves and ply orientations in a laminate, a complete analytical model was developed using local and global transfer matrices. The model predicted the transmitted signal amplitude as a function of polarization angle of the transmitter and time (or frequency) for a given laminate and input signal. To alleviate the experimental problems associated with shear wave coupling, electromagnetic acoustic transducers (EMATs) and metal delay lines were used in the angular scan of the transmitted signal. The EMAT system had the added advantage of being applicable to uncured composite laminates. Experiments were performed on both cured and uncured laminates with common layups for model verification. The sensitivity of the measured shear wave signals to fiber misorientation and stacking sequence errors was also demonstrated.

Acoustics↗
PubMed2002

Perspectives on protein evolution from simple exact models.

Understanding the evolution of biopolymers is important to rationalise the directed and undirected design of functional molecules. Large scale experiments or detailed computational studies are often impractical. Therefore, simple model systems, such as RNA secondary structure and lattice proteins have been adapted to study general statistical and topological features of genotype (sequence) to phenotype (structure) maps. We review findings from such models that address aspects of thermodynamic and mutational robustness, neutral evolution and recombination of proteins. We compare various modelling approaches, and discuss their generality, parameter dependency and experimental verifications of their predictions. The most striking observation is the universal emergence of neutral nets--sets of phenotypically identical genotypes that are interconnected by series of point mutations. However, fast adaptation by point mutations appears to be problematic for proteins. This may explain why proteins appear to be more specific while RNA is rather versatile. This could even be the reason why RNA had to evolve before proteins. Similar principles of biological organisation are reflected in sequence and structure databases of real proteins. Insights gained from modelling are useful for designing more efficient database organisation and search strategies.

Biopolymers↗
PubMed1998

An example of a protein ligand found by database mining: description of the docking method and its verification by a 2.3 A X-ray structure of a thrombin-ligand complex.

A computer program (SANDOCK) has been developed for the automated docking of small ligands to a target protein. It uses a guided matching algorithm to fit ligand atoms into the protein binding pocket. The protein is described by a modified Lee-Richard's dotted surface with each dot coded by chemical property and accessibility. Orientations of the ligand in the active site are generated such that a chemical and a shape complementary between the ligand and the active site cavity have to be fulfilled. The generated fits are evaluated with scoring functions which account for van der Waals, hydrophobic and hydrogen bonding interactions. This newly developed docking program can efficiently screen very large databases in a reasonable time and has been used to successfully identify novel ligands. The X-ray structure of a thrombin-ligand complex predicted by SANDOCK is described. The ligand binds to thrombin with a Kd of 65 microM and has an rmsd of 0.7 A for all ligand atoms from the predicted binding mode by SANDOCK.

Algorithms↗
PubMed2005

An allosteric model for heterogeneous receptor complexes: understanding bacterial chemotaxis responses to multiple stimuli.

The classical Monod-Wyman-Changeux model for homogeneous allosteric protein complex is generalized in this article to model the responses of heterogeneous receptor complexes to multiple types of ligand stimulus. We show that the recent in vivo experimental data of Escherichia coli chemotaxis responses for mutant strains with different expression levels of the chemo-receptors to different types of stimulus [Sourjik, V. & Berg, H. C. (2004) Nature 428, 437-441] all can be explained consistently within this generalized Monod-Wyman-Changeux model. Based on the model and the existing data, responses of all of the strains (studied in this article) to the presence of any combinations of ligand (Ser and MeAsp) concentrations are predicted quantitatively for future experimental verification. Through modeling the in vivo response data, our study reveals important information about the properties of different types of individual receptors, as well as the composition of the cluster. The energetic contribution of the nonligand binding, cytoplasmic parts of the cluster, such as CheA and CheW, is also discussed. The generalized allosteric model provides a consistent framework in understanding signal integration and differentiation in bacterial chemotaxis. It should also be useful for studying the functions of other heterogeneous receptor complexes.

Bacterial Physiological Phenomena↗
PubMed2000

History and radiographic findings associated with clinically suspected radial head subluxations.

OBJECTIVES: To determine: 1) physician practices regarding the use of radiographs for radial head subluxations (RHS), 2) the prevalence of missed fractures in children with a clinical diagnosis of RHS, 3) the relative risk of a fracture with a nonclassic history for mechanism of injury for RHS, and 4) radiographic findings associated with RHS that are difficult to reduce. METHODS: This study began with a physician survey that addressed the integration of radiographs into the management of RHS. We subsequently conducted a prospective randomized trial with a consecutive sampling of children less than 6 years of age who presented to one of 2 urban pediatric emergency departments and 2 suburban pediatric urgent care centers with a clinical diagnosis of RHS. After informed consent was obtained, reduction was undertaken with a maximum of four attempts (two by hyperpronation and two by supination/flexion), 15 minutes apart. Failure to reduce the RHS resulted in the procurement of a radiograph of the elbow. At the conclusion of the study, all radiographs were evaluated by a radiologist blinded to the diagnosis. Patients receiving radiographs were contacted 2 weeks after discharge for verification of the diagnosis. RESULTS: Eighty-four percent of 224 physicians returned completed surveys. Fifty-six percent reported using radiographs for failed reduction attempts. In the second phase of the study, 136 patients were enrolled prospectively: 127 were reduced successfully and 9 patients failed attempts at reduction. Of the nine patients receiving radiographs: four had fractures (prevalence of 2.9% with 95% confidence interval (CI) = 0.8-7.4), two had no radiographic findings and normal function on follow up, and three had isolated posterior fat pads on radiograph and normal function on follow-up. The relative risk of a fracture in children with a nonclassic history defined as any mechanism other than "pull" was 1.200 (95% CI = 0.441-3.264); the relative risk was 1.886 (95% CI = 0.680-5.231) when defining a nonclassic history as any mechanism other than "pull" or "fall." CONCLUSIONS: 1) Physicians tend to order radiographs for elbow injuries they initially perceive to be radial head subluxations when attempts at reduction fail. 2) In our study, fractures in children who presented with the classic flexed elbow/pronated wrist position were rare. 3) The relative risk of a fracture in children with a nonclassic history for mechanism of injury was not significant. 4) An isolated finding of a posterior fat pad in a child with RHS that is difficult to reduce was not associated with a fracture in our small sample of children with radiographic findings.

Child, Preschool↗
PubMed2001

Drug discovery and target validation.

Recent drug discovery has been driven largely by a genomics-based approach. This revolution in pharmaceutics is based on localized expression of either a novel gene or homologue of a known gene found in cDNA libraries made from normal versus diseased tissue. The choice and quality of cDNA library is critical for the success of this approach. Expression is normally verified at the cellular level by either immunocytochemistry or in situ hybridization. Activity of the recombinant protein in secondary cell-based assays allows highthroughput screens to be formulated to identify small-molecule effectors of this protein. More recently, a proteomics approach has also been incorporated into this process. This technology directly measures proteins whose expression is localized in disease tissue as the basis for cell-based screens to look for either activators or inhibitors, of this activity. The majority of screens are designed to look for inhibitors. Activity of small-molecules found by screening gives rise to pharmacokinetic studies and verification of activity in animal models of the disease. Structure-activity relationship (SAR) optimization of these small-molecules allows for suitable oral bioavailability and pharmacokinetics, resulting in compounds progressing from discovery to development. Based on these strategies, we have developed inhibitors of osteoclast-mediated bone resorption and are currently screening for bone anabolic agents. In addition, we have also developed small-molecule caspase inhibitors which prevent chondrocyte apoptosis and retain cell function in an attempt to find therapeutic agents to either prevent or treat osteoarthritis. These agents may well have utility in the treatment of temporomandibular joint diseases.

Animals↗
PubMed2005

Correction of accurate mass measurement for target compound verification by quadrupole time-of-flight mass spectrometry.

The aim of this work is to evaluate quadrupole/time-of-flight (QTOF) mass spectrometry for simultaneous measurement of accurate mass and quantification of a target by using a stable isotopically labeled internal standard. Mixtures of caffeine and (13)C(3)-caffeine (internal standard) at different concentration ratios were analyzed by capillary HPLC/QTOF. A calibration plot for quantification is linear over a factor of 20. Without invoking any correction scheme, the mass accuracy seriously degraded when the ratio of the mass standard to the test compound was not unity. The accuracy could be restored to approximately 2 ppm by using a quadratic function to correct the measured mass as a function of the measured signal ratio of target and internal calibrant.

Caffeine↗
PubMed1983

Diagnosis of exocrine pancreatic insufficiency from stool fat and weight.

Diagnostic workup was performed in 118 patients with a chronic malassimilation syndrome. 45 patients had exocrine pancreatic insufficiency, 23 patients jejunal mucosal atrophy (mainly celiac disease), 36 patients increased enteral deconjugation of bile acids and as shown by the 14C-glycocholate breath test and in 14 patients with chronic diarrhea and steatorrhea the cause could not be determined. Eleven patients with irritable bowel syndrome served as controls. Stool fat and weight were determined in all patients. Classification function coefficient were calculated on the basis of a discriminant analysis, leading to a correct classification in 82.2% of the patients with pancreatic insufficiency, 67.8% in the patients with jejunal mucosal atrophy and 83.3% in the patients with increased enteral deconjugation of bile acids. Calculation of sensitivity, specificity and predictive value in the total group and in two randomized subgroups and the correct diagnosis of exocrine pancreatic insufficiency in 78.5% of the patients of an independent verification group suggest clinical usefulness of this approach mainly in the diagnosis of exocrine pancreatic insufficiency.

Atrophy↗
PubMed2002

VERIDOS: a new tool for quality assurance for intensity modulated radiotherapy.

BACKGROUND: The use of intensity modulated radiation fields needs an extended quality assurance concept. This consists of a linac related part and a case related part. Case related means the verification of an individual treatment plan, optimized on a CT data set of an individual patient and prepared for the treatment of this patient. This part of the quality assurance work is usually time consuming, delivers only partially quantitative results and is uncomfortable without additional help. It will be shown in this paper how the software VERIDOS will improve the optimization of the case related part of the quality assurance work. MATERIAL AND METHODS: The main function of the software is the quantitative comparison of the calculated dose distribution from the treatment planning software with the measured dose distribution of an irradiated phantom. Several additional functions will be explained. Two self-developed phantoms made of RW3 (solid water) and GAFCHROMIC films or Kodak EDR2 films for the measurement of the dose distributions were used. VERIDOS was tested with the treatment planning systems Helay-TMS and Brainscan. RESULTS: VERIDOS is a suitable tool for the import of calculated dose matrices from the treatment planning systems Helax-TMS and Brainscan and of measured dose matrices exported from the dosimetry software Mephysto (PTW). The import from other treatment planning systems and scanning software applications for film dosimetry is generally possible. In such case the import function has to be adapted to the special header of the import matrix. All other functions of this software tool like normalization (automatically, manually), working with corrections (ground substraction, factors), overlay/comparison of dose distributions, difference matrix, cutting function (profiles) and export functions work reliable. CONCLUSIONS: VERIDOS improves the optimization of the case related part of the quality assurance work for intensity modulated radiation therapy (IMRT). The diverse functions of the software offer the radiation physicist a wide base to verify the IMRT plan independent from the mode of its delivery (compensator technology or MLC technology).

Dose Fractionation, Radiation↗
PubMed1997

Lichen sclerosus et atrophicus of the oral cavity: report of two cases.

Lichen sclerosus et atrophicus is a depigmenting mucocutaneous disease most frequently affecting the female genitalia. Genital lesions are symptomatic and may be functionally debilitating. Oral lesions are of little significance other than the esthetic concerns of perioral lesions. In view of the rarity of reported cases, one lesion of the labial mucocutaneous area and a second of the palate are presented along with a description of the disease's clinical and histopathologic findings and a brief review of the literature. The lip lesion was partially resolved with topical corticosteroids and was then fully eliminated with topical testosterone. Histologic verification and examination for the simultaneous occurrence or absence of oral and the more common genital-cutaneous lesions is essential if meaningful information in the medical-dental literature is to be obtained in the future.

Administration, Topical↗
PubMed2000

Insights into the rotary catalytic mechanism of F0F1 ATP synthase from the cross-linking of subunits b and c in the Escherichia coli enzyme.

The transmembrane sector of the F(0)F(1) rotary ATP synthase is proposed to organize with an oligomeric ring of c subunits, which function as a rotor, interacting with two b subunits at the periphery of the ring, the b subunits functioning as a stator. In this study, cysteines were introduced into the C-terminal region of subunit c and the N-terminal region of subunit b. Cys of N2C subunit b was cross-linked with Cys at positions 74, 75, and 78 of subunit c. In each case, a maximum of 50% of the b subunit could be cross-linked to subunit c, which suggests that either only one of the two b subunits lie adjacent to the c-ring or that both b subunits interact with a single subunit c. The results support a topological arrangement of these subunits, in which the respective N- and C-terminal ends of subunits b and c extend to the periplasmic surface of the membrane and cAsp-61 lies at the center of the membrane. The cross-linking of Cys between bN2C and cV78C was shown to inhibit ATP-driven proton pumping, as would be predicted from a rotary model for ATP synthase function, but unexpectedly, cross-linking did not lead to inhibition of ATPase activity. ATP hydrolysis and proton pumping are therefore uncoupled in the cross-linked enzyme. The c subunit lying adjacent to subunit b was shown to be mobile and to exchange with c subunits that initially occupied non-neighboring positions. The movement or exchange of subunits at the position adjacent to subunit b was blocked by dicyclohexylcarbodiimide. These experiments provide a biochemical verification that the oligomeric c-ring can move with respect to the b-stator and provide further support for a rotary catalytic mechanism in the ATP synthase.

Catalysis↗
PubMed1998

Software for constructing and verifying pedigrees within large genealogies and an application to the Old Order Amish of Lancaster County.

This paper describes PedHunter, a software package that facilitates creation and verification of pedigrees within large genealogies. A frequent problem in medical genetics is to connect distant relatives with a pedigree. PedHunter uses methods from graph theory to solve two versions of the pedigree connection problem for genealogies as well as other pedigree analysis problems. The pedigrees are produced by PedHunter as files in LINKAGE format ready for linkage analysis. PedHunter uses a relational database of genealogy data, with tables in specified format, for all calculations. The functionality and utility of PedHunter are illustrated by examples using the Amish Genealogy Database (AGDB), which was created for the Old Order Amish community of Lancaster County, Pennsylvania.

Christianity↗
PubMed2004

Low-flow vascular malformations: MR-guided percutaneous sclerotherapy in qualitative and quantitative assessment of therapy and outcome.

PURPOSE: To prospectively assess the therapeutic procedure and outcome of magnetic resonance (MR)-guided percutaneous sclerotherapy in patients with low-flow vascular malformations. MATERIALS AND METHODS: Seventy-six percutaneous sclerotherapy treatments were performed by one radiologist with real-time MR guidance in 15 patients (six female patients; mean age, 54.4 years +/- 11.1; nine male patients; mean age, 32.9 years +/- 14.1) with vascular malformations in the head and neck (n = 64), spine (n = 5), and extremities (n = 7). Qualitative assessment was used to analyze (a) individual success of therapy, (b) occurrence of complications, (c) time required for minimally invasive MR-guided sclerotherapy in regression analysis, (d) ability of MR imaging to depict postinterventional perfusion changes within the vascular malformation with calculation of changes in contrast-to-noise ratios, and (e) detection of volume changes at follow-up examinations with volumetric analysis. RESULTS: Percutaneous sclerotherapy was performed successfully and without complications by filling targeted vascular malformations with sclerosing agent. Induced vascular sclerosis was used to successfully treat individual predominant symptoms, such as hemorrhage, pain, cosmetic disfigurement, and functional impairment. Quantitative analysis focusing on the actual interventional length of time presented an acceleration over the 5-year time period, matching a cubic function in regression curve fit and taking 31 minutes 50 seconds +/- 14 minutes. Induced vascular thrombosis was identified in all treated portions on postinterventional images by the statistically significant changes in contrast-to-noise ratio (P < .05) compared with preinterventional imaging. On follow-up images (ie, those obtained after 12 weeks +/- 6), shrinkage was observed in targeted portions (67.2% +/- 18.9). CONCLUSION: MR imaging allows safe guidance and monitoring of minimally invasive sclerotherapy and permits verification of therapeutic success postinterventionally and during follow-up examinations.

Adolescent↗
PubMed2006

Hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an antigen to which the subject has been previously sensitized. The incidence of HP is unknown. A population-based study estimated the annual incidence of interstitial lung diseases as 30:100,000 and HP accounted for less than 2% of these cases. The diagnosis of HP can often be made or rejected with confidence, especially in areas of high or low prevalence respectively, using simple diagnostic criteria. Chest X-rays may be normal in active HP; High Resolution Computed Tomography is sensitive but not specific for the diagnosis of HP. The primary use of pulmonary function tests is to determine the physiologic abnormalities and the associated impairment. Despite the pitfalls of false positive and false negatives, antigen-specific IgG antibodies analysis can be useful as supportive evidence for HP. Bronchoalveolar lavage plays an important role in the investigation of patients suspected of having HP. A normal number of lymphocytes rules out all but residual disease. Surgical lung biopsy should be reserved for rare cases with puzzling clinical presentation or for verification the clinical diagnosis when the clinical course or response to therapy is unusual. Being an immune reaction in the lung, the most obvious treatment of HP is avoidance of contact with the offending antigen. Systemic corticosteroids represent the only reliable pharmacologic treatment of HP but do not alter the long-term outcome. The use of inhaled steroids is anecdotal. Treatment of chronic or residual disease is supportive.

Adult↗
PubMed2002

[Metformin has a positive effect on disorders of carbohydrate metabolism in long-term care with low doses of prednisone].

BACKGROUND: The influence of long-term, low doses of prednison administration (< 0.3 mg/kg/day) on glucoregulation and glucose tolerance was studied in 20 female patients (15-20 yrs), including verification of possibility to correct the impairment of glucose tolerance (IGT) by metformin (M). METHODS AND RESULTS: During prednison treatment, we found typical signs of insulin resistance manifestation: HOMAIR 3.55 (5.13), blood insulin/glucose ratio 3.8 (5.84), QUICKI 0.61 (0.124). These were associated with higher Langerhans (L.) islets hormone secretion detected under basal conditions as well as after bolus of 5 g arginine chloride. However, detailed analysis of hormone secretion ratios revealed distinct signs of L. islets function impairment and subcompensation. Specifically, low ratio C peptide/proinsulin and C peptide/glucagon were characteristicaly observed. Six months of M. administration (1000 mg/day) had a beneficial effect on glucose metabolisms deviations as indicated by the following: insulin resistance decreased (HOMAIR 1.96 (1.60), insulin/glucose ratio 2.34 (1.52), QUICKI increased at 0.699 (0.238)). At the same time we found a decrease in the basal levels of insulin, proinsulin, glucagon, C peptide and amyline, and AUC proinsulin and glucagon as well. HOMAsecretion decreased from an initial value of 389 (376) to 207 (119). CONCLUSIONS: Judging by the new hormonal secretion ratios, the L. islets' function following M. treatment substantially improved. From the clinical point of view, it is important to note that M. was tolerated very well. No patient interrupted the follow up because of M. intolerance. IGT in the whole group normalised, in spite of the fact that no accent was put on the regime, diet including. The 90% of lactate values did not exceed 1.7 mmol/l. Based on the results, we may conclude that M. has a beneficial effect on long-term, low doses of glucocorticoid-related (induced) glucose metabolism impairment, and therefore, M. administration could be recommended, particularly in the situations with higher levels of glycosylated hemoglobin.

Adolescent↗
PubMed2001

Point load wave excitation in multi-layered solids: experiments and model verification.

Studies of transient wave propagation in a single plate, a two-layer plate structure, and a two-layer-on-a-half-space structure are reported. Experimental results are used to verify the accuracy of a new model for wave propagation in layered solids. The experiments are performed using point load excitation and point detection at the surface of the layered structure. The basis of the new wave propagation model is first introduced. Then, experiments performed on a single plate are described. Results from different wave sources, plate materials, and wave sensors are compared with each other and with computed results from the model. The transient source function for a pencil-lead-break wave source is obtained. Next, the results of experiments performed on a two-layer plate structure (aluminum bonded to stainless steel) are reported. The cases of stainless steel atop aluminum and aluminum atop stainless steel are considered. The effects of the second layer on the transient displacement at the top surface are discussed. Finally, a two-layer-on-a-half-space structure consisting of a stainless steel plate as the top layer, an aluminum plate as the second layer and a thick acrylic resin block as the half-space is studied. The obtained experimental transient measurements agree with the computed results for all cases, thus verifying the accuracy of the model.

Journal Article↗