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At least 649 records · Page 36Linked to original sources
PubMed1989

A reference shape library for computer aided socket design in above-knee prostheses.

A Reference Library of socket shapes for an Above-Knee Computer Aided Socket Design (CASD) System has been created. This library forms part of a more general CASD System (Dean & Saunders, 1985; Novicov & Foort, 1982). It consists of a matrix of reference shapes representing above-knee socket characteristics and is based upon skeletal structure, residuum length and tissue mass. A set of 27 biomechanical reference shapes in the form of male plaster casts were produced by a combination of CNC milling and traditional artisan techniques. Each reference shape was digitized to obtain its cylindrical coordinates. Cross-sectional areas and tissue distributions within each shape and between the shapes were analyzed, modified and then stored numerically within the computer for further implementation of the CASD System for the above-knee amputees. The creation and the analysis of the reference shape data is described.

Artificial Limbs↗
PubMed2000

A knowledge model for analysis and simulation of regulatory networks.

MOTIVATION: In order to aid in hypothesis-driven experimental gene discovery, we are designing a computer application for the automatic retrieval of signal transduction data from electronic versions of scientific publications using natural language processing (NLP) techniques, as well as for visualizing and editing representations of regulatory systems. These systems describe both signal transduction and biochemical pathways within complex multicellular organisms, yeast, and bacteria. This computer application in turn requires the development of a domain-specific ontology, or knowledge model. RESULTS: We introduce an ontological model for the representation of biological knowledge related to regulatory networks in vertebrates. We outline a taxonomy of the concepts, define their 'whole-to-part' relationships, describe the properties of major concepts, and outline a set of the most important axioms. The ontology is partially realized in a computer system designed to aid researchers in biology and medicine in visualizing and editing a representation of a signal transduction system.

Animals↗
PubMed1999

Electronic medical record in the intensive care unit.

The EMR in the ICU has the utility of providing the necessary information to make sound clinical decisions for critically ill patients. For it to be optimized, the EMR must be more than just what is being replicated in the written record or merely a documentation tool; it must add value that supports and enhances clinical decision support. The EMR is too expensive a tool just to be a computer designed to ease documentation and retrieve data faster. Gardner and Huff have suggested that the EMR must answer three questions: Why, What, and So What. The "Why" is relatively easy to answer, but the "What" data to use so that the information is meaningful to a provider and the "So What" are more difficult to answer. Provided one can qualitatively assess "What" information is important for a health care provider, then "So What" becomes an important objective in the empirical quantification of the benefits that the EMR provides. It is clear that to analyze some of the outcomes that health care delivery provides, one needs some mechanism to automate the information at the point of care, particularly now that the regulatory agencies are requiring it. Given the fact that there is no single integrated computerized patient record, this becomes the daunting task for the next century. Making it easier for health care providers to interact with the system and providing them with instantaneous feedback that changes their medical decision so they can deliver better care (clinical pathways, clinical practice guidelines) will be the task required of the next generation of CISs.

Computer Systems↗
PubMed2000

Ligand-induced conformational changes in tissue transglutaminase: Monte Carlo analysis of small-angle scattering data.

Small-angle neutron and x-ray scattering experiments have been performed on type 2 tissular transglutaminase to characterize the conformational changes that bring about Ca(2+) activation and guanosine triphosphate (GTP) inhibition. The native and a proteolyzed form of the enzyme, in the presence and in the absence of the two effectors, were considered. To describe the shape of transglutaminase in the different conformations, a Monte Carlo method for calculating small-angle neutron scattering profiles was developed by taking into account the computer-designed structure of the native transglutaminase, the results of the Guinier analysis, and the essential role played by the solvent-exposed peptide loop for the conformational changes of the protein after activation. Although the range of the neutron scattering data is rather limited, by using the Monte Carlo analysis, and because the structure of the native protein is available, the distribution of the protein conformations after ligand interaction was obtained. Calcium activation promotes a rotation of the C-terminal with respect to the N-terminal domain around the solvent-exposed peptide loop that connects the two regions. The psi angle between the longest axes of the two pairs of domains is found to be above 50 degrees, larger than the psi value of 35 degrees calculated for the native transglutaminase. On the other hand, the addition of GTP makes possible conformations characterized by psi angles lower than 34 degrees. These results are in good agreement with the proposed enzyme activity regulation: in the presence of GTP, the catalytic site is shielded by the more compact protein structure, while the conformational changes induced by Ca(2+) make the active site accessible to the substrate.

Calcium↗
PubMed1996

Significant progression of white matter lesions and small deep (lacunar) infarcts in patients with stroke.

OBJECTIVE: To investigate whether the extent of white matter lesions (WMLs) and the number of small deep infarcts and territorial infarcts progress over time in patients with stroke and to test the hypothesis that WMLs are associated with small deep infarcts. DESIGN: Computed tomographic follow-up study in a cohort of 107 patients with ischemic stroke (median follow-up, 3.0 years). SETTING: Primary and referral care center. PATIENTS: Sixty-three of 144 registered patients with a first-ever symptomatic lacunar stroke and 44 of 155 with a territorial stroke entered this study. Forty-seven (33%) of the nonparticipating patients with a lacunar stroke and 54 (35%) of those with a territorial stroke died, and 34 (24%) and 57 (37), respectively, refused computed tomographic follow-up. MAIN OUTCOME MEASURES: The extent of the WMLs and the number of small deep and territorial infarcts on computed tomographic scans at study entry and at follow-up. RESULTS: Progression of WMLs occurred in 26 patients (26%), and multivariate regression analysis showed that it was associated with symptomatic lacunar stroke at study entry (adjusted odds ratio [aOR], 5.0; 95% confidence interval [CI], 1.2-20.3), silent small deep infarcts at study entry (aOR, 6.0, 95% CI, 1.0-34.6), old age (aOR, 5.5; 95% CI, 1.3-23.1), and longer follow-up (aOR, 12.7; 95% CI, 1.8-89.0). We found progression of small deep infarcts in 41 patients (38%). The progression was associated with symptomatic lacunar stroke at study entry (aOR, 27.7; 95% CI, 6.3-120.9) and longer follow-up (aOR, 7.7; 95% CI, 1.4-41.3). Progression of both WMLs and small deep infarcts, which occurred in 16 patients (16%), was associated with symptomatic lacunar stroke at study entry (aOR, 34.1; 95% CI, 2.5-471.7), silent small deep infarcts at study entry (aOR, 12.5; 95% CI, 1.4-112.0), and longer follow-up (aOR, 29.7; 95% CI, 1.8-501.0). The number of territorial infarcts increased in 14 patients (13%). The increase was associated with symptomatic territorial stroke at study entry (aOR, 7.9; 95% CI, 1.5-40.8) and a history of ischemic heart disease (aOR, 6.6; 95% CI, 1.3-34.8). CONCLUSIONS: The marked progression of WMLs and small deep infarcts that occurred mainly in patients with lacunar stroke suggests that both WMLs and small deep (lacunar) infarcts are caused by a similar vasculopathy that affects small vessels, which is progressive despite standard stroke treatment.

Adult↗
PubMed1996

Genetic factors for the development of Alzheimer disease in the Cherokee Indian.

OBJECTIVE: To study the relationship between the genetic degree of Cherokee ancestry, the apolipoprotein E *E4 (APOE*E4) allele type, and the development of Alzheimer disease (AD) in individuals from the Cherokee Nation who reside in northeastern Oklahoma. SETTING: Alzheimer disease center satellite clinic and university departments of neurology, psychiatry, and academic computing. DESIGN: Standardized dementia evaluations based on criteria from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association were performed on 26 patients aged 65 years or older to establish a diagnosis of AD. Twenty-six control subjects were recruited and similarly assessed. The APOE allele type determinations were obtained on all patients and control subjects. Appropriate statistical analyses were used to compare the genetic degree of Cherokee ancestry, the APOE allele type, and the development of AD. RESULTS: The data indicated that as the genetic degree of Cherokee Indian ancestry increased, the representation of AD decreased. The 9 patients with AD with a greater than 50% genetic degree of Cherokee ancestry constituted 35% of the group with AD. The 17 remaining patients with AD who were less than 50% Cherokee constituted 65% of the group with AD. In contrast, 17 (65%) of the control subjects were more than 50% Cherokee; only 9 (35%) were less than 50% Cherokee. These percentages of AD were not changed by the *E4 allele. This inverse relationship between the genetic degree of Cherokee ancestry and AD, independent of the APOE*E4 allele status, diminished with increasing age, suggesting an age-related protective effect of being Cherokee. For a decrease of 10% in Cherokee ancestry, the odds of developing AD are estimated to be 9.00 times greater at age 65 years but only 1.34 times greater at age 80 years. CONCLUSIONS: A greater genetic degree of Cherokee ancestry reduces the risk of developing AD and, thus, seems protective. This protective genetic factor is independent of APOE allele type and diminishes with age.

Aged↗
PubMed2006

Benign tremulous parkinsonism.

BACKGROUND: Benign tremulous parkinsonism has never been precisely defined nor has the long-term course been studied. OBJECTIVE: To report the clinical features and longitudinal course of patients with benign tremulous parkinsonism encountered in our movement disorders practice. DESIGN: Computer search of medical records database. SETTING: Mayo Clinic, Rochester, Minn. PATIENTS: Of 116 patients identified, 16 (10 male and 6 female) had at least an 8-year history of this disease, had been examined by a senior movement disorders specialist, and had ultimately been diagnosed as having benign tremulous parkinsonism after an initial diagnosis of Parkinson disease (PD). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Age at onset of disease, response to levodopa therapy, tremor characteristics, and family history. RESULTS: Mean disease duration was 11 years (range, 8-25 years) at last follow-up. Mean age at onset, 58.5 years, was younger than in most PD series, and most patients had a poor levodopa response (although levodopa trials were inadequate in some). A moderate to marked postural tremor was noted in 13 of the 16 patients, including 6 with a kinetic tremor. A family history of PD and/or tremor was reported in 10 (63%) of our patients. Three patients required thalamic deep brain surgery to treat their tremor. CONCLUSIONS: Benign tremulous parkinsonism may be a distinct clinical entity characterized by tremor predominance plus minimal progression of other aspects of parkinsonism. The tremor is often not very responsive to levodopa therapy. In this series, most patients had immediate family members with a diagnosis of tremor or PD.

Adult↗
PubMed2005

Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness.

OBJECTIVE: To analyze the physical manifestations and genetic features of 2 families segregating X-linked deafness, which is most commonly reported to be caused by mutations of the POU domain gene POU3F4 at the DFN3 locus. DESIGN: Computed tomographic study of the temporal bone in probands from each family, followed by mutation screening and deletion mapping of POU3F4 in family members. SETTING: Two midwestern genetics clinics. PARTICIPANTS: Two families with X-linked deafness. MAIN OUTCOME MEASURES: Anomalies of the inner ear in the probands; results of gene mapping and severity and effects of hearing loss in the family members. RESULTS: In the first family, a large deletion was identified that includes POU3F4 and extends upstream approximately 530 kilobases; in the second family, a novel serine-to-leucine (S228L) amino acid mutation was identified in the POU-specific domain of POU3F4. Both the deletion and the missense mutation segregate with the clinical phenotype and are causally related to the deafness in these families. CONCLUSIONS: Deafness related to the POU3F4 gene is associated with dilation of the internal auditory canal and a spectrum of other temporal bone anomalies that range in severity from mild to severe dysplasia of the cochlea and semicircular canals. The consequence of these anomalies is a congenital mixed hearing loss, the sensorineural component of which progresses over time. Affected males can also present with vestibular dysfunction that is associated with delayed developmental motor milestones. Intrafamilial variability occurs.

Chromosome Deletion↗
PubMed1994

The 24-hour profiles of cortisol, prolactin, and growth hormone secretion in mania.

OBJECTIVE: To characterize sleep and the 24-hour profiles of cortisol, prolactin (PRL), and growth hormone (GH) secretion in mania. METHODS: Blood was sampled at 15-minute intervals, and sleep was polygraphically recorded in eight unmedicated male patients with pure mania and the results compared with those from a group of 14 healthy age-matched controls. The circadian, sleep-related, and pulsatile hormonal variations were quantitatively characterized using specifically designed computer algorithms. RESULTS: The manic state was associated with alterations of corticotropic activity and circadian rhythmicity partially overlapping those previously observed in acute endogenous depression, consisting of an elevation of nocturnal cortisol levels and an early timing of the nadir of the circadian variation. Sleep onset was delayed and the sleep period was reduced. A trend for short rapid eye movement latencies was apparent in the adult patients. Both the amount and the temporal organization of PRL and GH secretion were normal. CONCLUSION: The manic state seems to be characterized by similar but less severe neuroendocrine and circadian abnormalities, compared with major depression.

Acute Disease↗
PubMed1986

Effect of controlled dietary consistency and cage environment on the rat mandibular growth.

Forty Fischer strain inbred albino rats, evenly divided by sex, were obtained at 9 days of age. The animals were weaned at 21 days and randomly divided into the four experimental groups. Two variations on dietary consistency, hard and soft diet, as well as two variations on cage environment, normal and no biting surfaces, constituted the experimental groupings. The experimental period consisted of 16 weeks during which the animals were raised under the designated conditions. At the end of the experimental period the animals were killed with carbon dioxide, and the entire mandible, and both femurs, were dissected free. Weight and volumetric analysis were carried out in a standard fashion on the cleaned specimens. Area and linear measurements were performed and analyzed with a specially designed computer program. The results showed that there was sexual dimorphism in the Fischer rat both with respect to body weight and the weight, volume, area, and linear measurements of the mandible. The effects of dietary consistency had a greater influence on mandibular ramus size and form than did those caused by alteration in cage environment. The posterior region of the mandible, in association with the heavy muscles of mastication, was affected more by dietary consistency than was the anterior region. The entire region of the mandibular ramus acted as an area of adaptation and growth. The findings of this study indicate that dietary consistency has a small but significant effect on mandibular size in specific measurements. The cage environment used in this experiment did not limit function to the extent necessary to see measurable changes in mandibular measurements.

Animal Husbandry↗
PubMed2004

mRNA openers and closers: modulating AU-rich element-controlled mRNA stability by a molecular switch in mRNA secondary structure.

Approximately 3 000 genes are regulated in a time-, tissue-, and stimulus-dependent manner by degradation or stabilization of their mRNAs. The process is mediated by interaction of AU-rich elements (AREs) in the mRNA's 3'-untranslated regions with trans-acting factors. AU-rich element-controlled genes of fundamentally different functional relevance depend for their activation on one positive regulator, HuR. Here we present a methodology to exploit this central regulatory process for specific manipulation of AU-rich element-controlled gene expression at the mRNA level. With a combination of single-molecule spectroscopy, computational biology, and molecular and cellular biochemistry, we show that mRNA recognition by HuR is dependent on the presentation of the sequence motif NNUUNNUUU in single-stranded conformation. The presentation of the HuR binding site in the mRNA secondary structure appears to act analogously to a regulatory on/off switch that specifically controls HuR access to mRNAs in cis. Based on this finding we present a methodology for manipulating ARE mRNA levels by actuating this conformational switch specifically in a target mRNA. Computationally designed oligonucleotides (openers) enhance the NNUUNNUUU accessibility by rearranging the mRNA conformation. Thereby they increase in vitro and endogenous HuR-mRNA complex formation which leads to specific mRNA stabilization (as demonstrated for TNFalpha and IL-2, respectively). Induced HuR binding both inside and outside the AU-rich element promotes functional IL-2 mRNA stabilization. This opener-induced mRNA stabilization mimics the endogenous IL-2 response to CD28 stimulation in human primary T-cells. We therefore propose that controlled modulation of the AU-rich element conformation by mRNA openers or closers allows message stabilization or destabilization in cis to be specifically triggered. The described methodology might provide a means for studying distinct pathways in a complex cellular network at the node of mRNA stability control. It allows ARE gene expression to be potentially silenced or boosted. This will be of particular value for drug-target validation, allowing the diseased phenotype to ameliorate or deteriorate. Finally, the mRNA openers provide a rational starting point for target-specific mRNA stability assays to screen for low-molecular-weight compounds acting as inhibitors or activators of an mRNA structure rearrangement.

Antigens, Surface↗
PubMed2003

Zwitterionic silenes: interesting goals for synthesis?

Properties of silenes, as a function of increased reversal of the Si=C bond polarity, have been examined through quantum-chemical calculations. The aim of this study was to identify silenes that can be of general interest for organic synthesis. The calculations were carried out primarily with the B3LYP hybrid density functional method, but also with the CASSCF, MP2, MP4(SDQ), and CCSD(T) methods. The study was performed on Z(2)Si=CXY compounds which were divided into three sets that differ with regard to their Si substituents (Z), and with their C substituents (X and Y) varying from weakly to strongly pi-electron-donating groups. The charge at the Si atom (q(Si)) was used as a measure of the extent of reversed silicon-carbon bond polarity. For each of the three sets, the variation in silicon-carbon bond lengths (r(Si=C)) and extent of Si pyramidalization (SigmaSi) in relation to q(Si) follow three separate curves. Silenes with strongly pi-electron-donating X and Y groups are completely described by zwitterionic (reverse-polarized) resonance structures. Such zwitterionic silenes are singly (Si=C) rather than doubly bonded (Si=C), and have a distinctly pyramidal Si atom due to negative charge localization. These silenes also have much lower heats of dimerization than the parent silene. Finally, inversion barriers of zwitterionic silenes are increased by electron-withdrawing substituents, and this enables computational design of silenes with their Si atoms as chiral centers. It is hoped that such chiral zwitterionic silenes can find use in organic synthesis.

Journal Article↗
PubMed1985

Tests of homogeneity and trend with medians.

Algorithms for tests of homogeneity and trend with medians are presented. Under certain conditions the tests are more efficient than many standard nonparametric tests on one-way classification designs. Computationally the tests are very simple and could be performed by hand or with the help of a calculator. Application to certain types of data derived in cytogenetics is pointed out with an example.

Animals↗
PubMed2004

The effects of curing history on residual stresses in bone cement during hip arthroplasty.

During cement curing in total hip arthroplasty, residual stresses are introduced in the cement mantle as a result of curing shrinkage, thermal shrinkage, and geometrical constraints. These high residual stresses are capable of initiating cracks in the mantle of cemented hip replacements. The purpose of this study was to determine the residual stresses in the cemented hip replacements. The finite element method was developed to predict the residual stresses built up in joint arthroplasties. Experimental tests were then performed to validate the numerical methodology. Then the effects of curing history on the residual stress distribution were investigated with finite element simulations. Results showed that the predictions of the thermal shrinkage residual stresses by the developed method agreed with the experimental tests very well. The residual stress buildup was shown to depend on the curing history. By preheating the prosthesis stem prior to implantation, a desired low-level residual stress at the critical prosthesis-cement interface was obtained. As a result, this article provides a numerical tool for the quantitative simulation of residual stress and for examining and refining new designs computationally.

Arthroplasty, Replacement, Hip↗
PubMed1992

Tumor necrosis factor-alpha decreases neutrophil chemotaxis to N-formyl-1-methionyl-1-leucyl-1-phenylalanine: analysis of single cell movement.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine produced by mononuclear cells in response to endotoxin, inhibits neutrophil chemotaxis. We analyzed the effects of TNF-alpha on the orientation and movement of individual neutrophils in a chemoattractant gradient. Neutrophils, treated or untreated with TNF-alpha, were observed migrating in a gradient of the chemotactic peptide N-formyl-1-methionyl-1-leucyl-1-phenylalanine (fMLP) on a specially constructed chamber (Zigmond bridge). The movement of these cells was videotaped, digitized, and then tracked using a newly designed computer algorithm. The data obtained from this algorithm were then utilized to calculate distance traveled, speed and ability to polarize and migrate in a directed manner for each individual cell. TNF-alpha-treated cells behaved like cells not exposed to fMLP in that they failed to orient in a chemotactic gradient and moved in a manner similar to randomly migrating cells. This study provides unique observations of the effect of TNF-alpha on multiple parameters of PMN migration.

Algorithms↗
PubMed1995

1H-NMR microscopy of tablets.

A 1H-nuclear magnetic resonance (NMR) microscopy method was utilized for the first time to determine the porosity distribution of physically intact tablets. The main advantage of this newly developed method was that porosity cross sections through whole tablets or specific locations could be obtained without mechanically destroying the tested tablet. This was achieved by filling tablet cavities with silicone oil under vacuum. The amount of silicone oil locally within the tablet was then determined by 1H-NMR microscopy, revealing the inverse inner structure. To reduce the measuring time, a paramagnetic gadolinium complex was added to the silicone oil. The cross sectional signals produced by 1H-NMR microscopy through the tablet were transformed into a color image by a specially designed computer graphic program. To improve the signal-noise ratio an algorithm of 3D-filtering was introduced. The maximal spatial resolution achieved with this method was about 95 microns for a cube's edge length corresponding to some 380,000 positions in a 9-mm-diameter compression-coated tablet. Uneven porosity distributions within tablets, cracks, or cavities could be visualized with this newly developed method. Different compaction mechanisms were observed with plastic- or brittle-type tablets. The different states of densification during compaction of powders could be detected. The integrity of compression coatings was determined to be dependent on the pressure load and the location of the core within the coat.

Magnetic Resonance Imaging↗
PubMed1994

Assembly of ordered contigs of cosmids selected with YACs of human chromosome 13.

We have developed an efficient method for assembling ordered cosmid contigs aligned to mega-YACs and midi-YACs (average insert sizes of 1.0 and 0.35 Mb, respectively) and used this general method to initiate high-resolution physical mapping of human chromosome 13 (Chr 13). Chr 13-enriched midi-YAC (mYAC) and mega-YAC (MYAC) sublibraries were obtained from corresponding CEPH total human YAC libraries by selecting colonies with inter-Alu PCR probes derived from Chr 13 monochromosomal cell hybrid DNA. These sublibraries were arrayed on filters at high density. In our approach, the MYAC 13 sublibrary is screened by hybridization with cytogenetically assigned Chr 13 DNA probes to select one or a small subset of MYACs. Inter-Alu PCR products from each MYAC are then hybridized to the MYAC and mYAC sublibraries to identify overlapping YACs and to an arrayed Chr 13-specific cosmid library to select corresponding cosmids. The set of selected cosmids, gridded on filters at high density, is hybridized with inter-Alu PCR products from each of the overlapping YACs to identify subsets of cosmids and also with riboprobes from each cosmid of the arrayed set ("cosmid matrix cross-hybridization"). From these data, cosmid contigs are assembled by a specifically designed computer program. Application of this method generates cosmid contigs spanning the length of a MYAC with few gaps. To provide a high-resolution map, ends of cosmids are sequenced at preselected sites to position densely spaced sequence-tagged sites.

Base Sequence↗
PubMed2001

Influence of intercodon and base frequencies on codon usage in filarial parasites.

Base frequency, codon usage, and intercodon identity were analyzed in five filarial parasite species representing five Onchocercidae genera. Wucheria bancrofti, Brugia malayi, Onchocerca volvulus, Acanthocheilonema viteae, and Dirofilaria immitis gene sequences were downloaded from NCBI, and analysis was performed using locally designed computer programs and other freely available applications. A clear sequence bias was observed among the nematode species examined. At the nucleotide level, AT basepairs were present in gene sequences at higher frequencies than GC. In addition, codons ending in A or T were used proportionately more than those with G or C in the third-codon position. In addition, the amino acids used most often corresponded to codons ending in AT basepairs. Intercodon base proportion was biased in that A was found most often at N4, second only to T in certain specific cases. Since all of these sequence biases were observed in a relatively consistent fashion among all of the organisms studied, we conclude that sequence bias is a genetic characteristic, which is associated with multiple filarial genera.

Animals↗