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PubMed1990

Metadata-based generation and management of knowledgebases from molecular biological databases.

Present-day knowledge-based systems (or expert systems) and databases constitute 'islands of computing' with little or no connection to each other. The use of software to provide a communication channel between the two, and to integrate their separate functions, is particularly attractive in certain data-rich domains where there are already pre-existing database systems containing the data required by the relevant knowledge-based system. Our evolving program, GENPRO, provides such a communication channel. The original methodology has been extended to provide interactive Prolog clause input with syntactic and semantic verification. This enables automatic generation of clauses from the source database, together with complete management of subsequent interfacing to the specified knowledge-based system. The particular data-rich domain used in this paper is protein structure, where processes which require reasoning (modelled by knowledge-based systems), such as the inference of protein topology, protein model-building and protein structure prediction, often require large amounts of raw data (i.e., facts about particular proteins) in the form of logic programming ground clauses. These are generated in the proper format by use of the concept of metadata.

Artificial Intelligence↗
PubMed2006

Artificial neural network based identification of Campylobacter species by Fourier transform infrared spectroscopy.

Two prototypes of artificial neural network (ANN), multilayer perceptron (MLP), and probabilistic neural network (PNN), were used to analyze infrared (IR) spectral data obtained from intact cells belonging to the species Campylobacter coli and Campylobacter jejuni. In order to establish a consistent identification and typing procedure, mid infrared spectra of these species were obtained by means of a Fourier transform infrared (FT-IR) spectroscope. FT-IR patterns belonging to 26 isolates subclassified into 4 genotypes were pre-processed (normalized, smoothed and derivatized) and grouped into training, verification and test sets. The two architectures tested (PNN, MLP) were developed and trained to identify or leave unassigned a number of IR patterns. Two window ranges (w(4), 1200 to 900 cm(-1); and w(5), 900 to 700 cm(-1)) in the mid IR spectrum were presented as input to the ANN models functioning as pattern recognition systems. No matter the ANN used all the training sets were correctly identified at subspecies level. For the test set, the four-layer MLP network was found to be specially suitable to recognize FT-IR data since it correctly identified 99.16% of unknowns using the w(4) range, and was fully successful in detecting atypical patterns from closely related Campylobacter strains and other bacterial species. The PNN network obtained lower percentages in assignation and rejection. Overall, ANNs constitute an excellent mathematical tool in microbial identification, since they are able to recognize with a high degree of confidence typical as well as atypical FT-IR fingerprints from Campylobacter spp.

Campylobacter↗
PubMed1994

The temperature-composition phase diagram of monomyristolein in water: equilibrium and metastability aspects.

The temperature-composition phase diagram of monomyristolein in water was constructed using x-ray diffraction. Low- and wide-angle diffraction patterns were collected from samples of fixed hydration as a function of temperature in the heating direction on x-ray-sensitive film and/or image plates. The phases identified in the system include the lamellar crystalline phase, the lamellar liquid crystalline phase, the fluid isotropic phase, and two inverted cubic phases. Particular attention has been devoted to the issues of phase equilibrium and phase boundary verification. Cubic phase undercooling was examined by adjusting the temperature of several samples in the cubic phase to a value where the lamellar liquid crystalline phase represents equilibrium behavior. Cooling-induced structure and phase changes were monitored continuously over a 30-min period by recording low-angle diffraction patterns from the samples using a streak camera. The cubic-to-lamellar transition rate decreased with increasing sample hydration. Additionally, the transition proceeded more rapidly at an incubation temperature of 25 degrees C compared to that at 0 degrees C. A mechanism is proposed that accounts for the hydration and temperature sensitivity of the phase transition under nonequilibrium conditions.

Biophysical Phenomena↗
PubMed2002

Family with acute myelocytic leukemia, breast, ovarian, and gastrointestinal cancer.

We report a multigeneration family in which hematologic cancers, particularly acute myelocytic leukemia (AML), and solid tumors were interspersed in cancer-prone lineages consistent with an autosomal dominant mode of genetic transmission. This combination of AML and solid tumors, in the absence of a known hereditary disorder such as the Li-Fraumeni syndrome, appears to be unique. This pedigree appears to support our hypothesis of a genetic susceptibility to both solid tumors and hematologic cancer in this kindred. Our study involved the genetic work-up of the family and the education of high-risk patients. Medical and pathology reports were retrieved for cross-referencing and verification of family reports. Blood collected through venipuncture and, when available, diagnostic bone marrow specimens were obtained for cytogenetic studies, inclusive of multiflour fluorescence in situ hybridization (M-FISH) and G-banding methods. Slides and tissue blocks were reviewed, when available. No constitutional chromosomal abnormality or rearrangement and no abnormal platelet count or function was identified in cancer-affected members or high-risk relatives in this family. However, two family members affected with AML exhibited abnormal acquired clones in their bone marrow specimens by both G-band studies and interphase FISH, both with a deletion of 5q.

Bone Marrow↗
PubMed2004

Transcriptional profiling of estrogen-regulated gene expression via estrogen receptor (ER) alpha or ERbeta in human osteosarcoma cells: distinct and common target genes for these receptors.

Estrogens exert many important effects in bone, a tissue that contains both estrogen receptors alpha and beta (ERalpha and ERbeta). To compare the actions of these receptors, we generated U2OS human osteosarcoma cells stably expressing ERalpha or ERbeta, at levels comparable with those in osteoblasts, and we characterized their response to 17beta-estradiol (E2) over time using Affymetrix GeneChip microarrays to determine the expression of approximately 12,000 genes, followed by quantitative PCR verification of the regulation of selected genes. Of the approximately 100 regulated genes we identified, some were stimulated by E2 equally through ERalpha and ERbeta, whereas others were selectively stimulated via ERalpha or ERbeta. The E2-regulated genes showed three distinct temporal patterns of expression over the 48-h time course studied. Of the functional categories of the E2-regulated genes, most numerous were those encoding cytokines and factors associated with immune response, signal transduction, and cell migration and cytoskeleton regulation, indicating that E2 can exert effects on multiple pathways in these osteoblast-like cell lines. Of note, E2 up-regulated several genes associated with cell motility selectively via ERbeta, in keeping with the selective E2 enhancement of the motility of ERbeta-containing cells. On genes regulated equally by E2 via ERalpha or ERbeta, the phytoestrogen genistein preferentially stimulated gene expression via ERbeta. These studies indicate both common as well as distinct target genes for these two ERs, and identify many novel genes not previously known to be under estrogen regulation.

Bone Neoplasms↗
PubMed2005

Electron beam treatment verification using measured and Monte Carlo predicted portal images.

Electron beam treatments may benefit from techniques to verify patient positioning and dose delivery. This is particularly so for complex techniques such as mixed photon and electron beam radiotherapy and electron beam modulated therapy. This study demonstrates that it is possible to use the bremsstrahlung photons in an electron beam from a dual scattering foil linear accelerator to obtain portal images of electron beam treatments. The possibility of using Monte Carlo (MC) simulations to predict the electron beam treatment portal images was explored. The MC code EGSnrc was used to model a Varian CL21EX linear accelerator (linac) and to characterize the bremsstrahlung photon production in the linac head. It was found that the main sources of photons in the electron beam are the scattering foils, the applicator and the beam-shaping cut-out. Images were acquired using the Varian CL21EX linac and the Varian aS500 electronic portal imager (EPI); four electron energies (6, 9, 12, 16 MeV), and different applicator and cut-out sizes were used. It was possible to acquire images with as little as 10.7 MU per image. The contrast, the contrast-to-noise ratio (CNR), the signal-to-noise ratio (SNR), the resolution and an estimate of the modulated transfer function (MTF) of the electron beam portal images were computed using a quality assurance (QA) phantom and were found to be comparable to those of a 6 MV photon beam. Images were also acquired using a Rando anthropomorphic phantom. MC simulations were used to model the aS500 EPID and to obtain predicted portal images of the QA and Rando phantom. The contrast in simulated and measured portal images agrees within +/-5% for both the QA and the Rando phantom. The measured and simulated images allow for a verification of the phantom positioning by making sure that the structure edges are well aligned. This study suggests that the Varian aS500 portal imager can be used to obtain patient portal images of electron beams in the scattering foil linacs.

Computer Simulation↗
PubMed1986

Membrane transport: a mathematical investigation.

It is known that the primary constituents of the membranes of cells are lipids. These lipids are arranged in two layers and the membrane is frequently called a bilipid layer. Recent low intensity scanning electron micrographs of the bilipid layer has revealed that the bilipid layer has revealed that the bilipid membrane layer also contains proteins. The proteins in the bilipid membrane layer pass from one side of the layer to the other and thus constitute a "hole" in the membrane layer. The structure of the proteins is such that an essentially void space exists surrounded by the molecular structures of the protein. The exact functioning of the proteins has not yet been determined. The thesis of this paper is that the proteins act as mediators for the transport of specific catabolites. The supporting arguments for the thesis are in the form of mathematical models for the catabolite - protein interactions, and the results of simulations based upon the mathematical models. Physical verifications of the results presented in this paper await physiological experimental data. However the results of this work indicate that modest changes in the membrane proteins result in a significant change in the amount of catabolite transported across the cell membrane. The mediation of the catabolite transport by the proteins has the pathological implications that long term post-disease states of the cells may be linked closely to the altered states of the membrane proteins: which may occur during the period of the disease state.

Biological Transport↗
PubMed2005

Dynamic characterization of hysteresis elements in mechanical systems. I. Theoretical analysis.

The pre-sliding-pre-rolling phase of friction behavior is dominated by rate-independent hysteresis. Many machine elements in common engineering use exhibit, therefore, the characteristic of "hysteresis springs," for small displacements at least. Plain and rolling element bearings that are widely used in motion guidance of machine tools are typical examples. While the presence of a hysteresis element may mark the character of the resulting dynamics, little is to be found about this topic in the literature. The study of the nonlinear dynamics caused by such elements becomes imperative if we wish to achieve accurate control of such machines. In this Part I of the investigation, we examine a single-degree-of-freedom mass-hysteresis-spring system and show that, while the free response case is amenable to an exact solution, the more important case of forced response has no closed form solution and requires other methods of treatment. We consider harmonic-balance analysis methods (which are common analysis tools in engineering) suitable for frequency-domain treatment, in particular the approximate describing function (DF) method, and compare those results with "exact" numerical simulations. The DF method yields basically a linear equation with amplitude-dependent modal parameters. We find that agreement in the frequency response function, between DF and exact solution, is good for small excitation amplitudes and for very large amplitudes. Intermediate values, however, show high sensitivity to amplitude variations and, consequently, no regular solution is obtainable by either approach. This appears to be an inherent property of the system pointing to the need for developing further analysis methods. Experimental verification of the analysis outlined in this Part I is given in Part II of the paper.

Fourier Analysis↗
PubMed1994

A data management program for the Electra 800 automatic analyser.

The Electra 800 automatic coagulation analyser rapidly performs most chronometric coagulation tests with high precision. To facilitate data handling, software, adaptable to any PC running under MS-DOS, was written to manage the analyser. Data are automatically collected via the RS232 interface or can be manually input. The software can handle 64 different analyses, all entirely 'user defined'. An 'electronic worksheet' presents the results in pages of ten patients. This enables the operator to assess the data and to perform verifications or complementary tests if necessary. All results outside a predetermined range can be flagged and results can be deleted, modified or added. A patient's previous files can be recalled as the data are archived at the end of the day. A 120 Mb disk can store approximately 130,000 patient files. A daily archive function can print the day's work in alphabetical order. A communication protocol allows connection to a mainframe computer. This program and the user's manual are available on request, free of charge, from the authors.

Autoanalysis↗
PubMed2001

The relationship between trauma center volume and outcome.

In spite of the limited direct evidence available, increasing data support a positive volume-outcome association in trauma care. When coupled with the extensive indirect data suggesting that regions with organized systems of trauma care are associated with lower trauma-related mortality rates than regions where the number of centers and their level of commitment are unlimited and untested, there is little doubt that experience improves outcome and that volume plays a critical role in the accrual of experience. Although regionalization of trauma care has the inevitable consequence of increased prehospital transport times, particularly in rural areas remote from large trauma centers, some states have designed inclusive systems where a large number of smaller centers have been verified and designated as lower level trauma centers (i.e., level 3-5). The process of trauma center verification holds these smaller volume centers to a standard of care such that the quality of care of the trauma patient may exceed that of other, less-regulated aspects of medical or surgical care. Several reports have suggested that trauma outcomes in smaller rural level 3 centers or centers with dedicated trauma programs with appropriate, functional triage protocols are comparable to national norms, thus reflecting the importance of commitment to outcome. These data suggest that quality of care does not only follow volume, particularly when stipulations and requirements are clear regarding the process of care and ongoing quality assurance.

Hospital Mortality↗
PubMed2004

Sublexical and lexical influences on gender assignment in French.

Two experiments showed that French native speakers rely on sublexical and lexical cues to allocate gender during word recognition. Sublexical cues were based on whether the word ending was typical for a particular gender rather than neutral with regard to gender. Lexical cues were based on whether the associated definite article was informative (for words beginning with a consonant) or uninformative (for words beginning with a vowel). Classification of single nouns and verification of grammatical combinations of indefinite article and noun led to longer times when both sublexical and lexical cues were uninformative compared with when one or both cues were informative. Verification of ungrammatical combinations of indefinite article and noun yielded separate effects of both cues, though only when monitoring for both semantic and syntactic unacceptability in meaningful phrases did people attend to both cues independently. It was argued that people became more cautious in their gender assignments as task requirements became "deeper": If strategic changes as a function of task demands are incorporated, the results are compatible with connectionist models proposing that gender decisions are computed from strength of past associations of the word and gender-specifying elements.

Adult↗
PubMed2004

Differentially expressed genes in HIV-1-infected macrophages following treatment with the virus-suppressive immunomodulator murabutide.

The synthetic immunomodulator murabutide has been found to suppress human immunodeficiency virus type-1 (HIV-1) replication, in macrophages, through a regulated expression of cellular factors needed at different steps in the virus replication cycle. To identify cellular genes implicated in the murabutide-induced virus inhibition, we have carried out a differential display analysis on HIV-1-infected macrophages that were treated, or not, with murabutide. Sequencing of the differentially regulated cDNA bands and verification of the reproducibility of the murabutide effects, by reverse transcription-polymerase chain reaction or by Northern blotting, revealed an up-regulated expression of 21 genes and a down-regulation of seven others. The murabutide-regulated genes encoded proteins implicated in DNA binding, regulation of transcription, oxidative stress, metal binding, and other physiological functions. Six of the genes corresponded to unassigned/expressed sequence tags with yet unknown function. Among the genes which were up-regulated by murabutide and with established effects on inhibiting virus transcription, was the octamer binding factor 1 (Oct-1). We demonstrate the ability of murabutide to induce enhanced Oct-1 protein expression and DNA-binding activity in macrophages. Furthermore, our findings suggest the potential implication of additional transcription factors and metal-binding proteins in mediating the inhibitory effect of murabutide on virus transcription.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2002

Behavioral characterization of mice lacking histamine H(3) receptors.

Brain histamine H(3) receptors are predominantly presynaptic and serve an important autoregulatory function for the release of histamine and other neurotransmitters. They have been implicated in a variety of brain functions, including arousal, locomotor activity, thermoregulation, food intake, and memory. The recent cloning of the H(3) receptor in our laboratory has made it possible to create a transgenic line of mice devoid of H(3) receptors. This paper provides the first description of the H(3) receptor-deficient mouse (H(3)(-/-)), including molecular and pharmacologic verification of the receptor deletion as well as phenotypic screens. The H(3)(-/-) mice showed a decrease in overall locomotion, wheel-running behavior, and body temperature during the dark phase but maintained normal circadian rhythmicity. H(3)(-/-) mice were insensitive to the wake-promoting effects of the H(3) receptor antagonist thioperamide. We also observed a slightly decreased stereotypic response to the dopamine releaser, methamphetamine, and an insensitivity to the amnesic effects of the cholinergic receptor antagonist, scopolamine. These data indicate that the H(3) receptor-deficient mouse represents a valuable model for studying histaminergic regulation of a variety of behaviors and neurotransmitter systems, including dopamine and acetylcholine.

Adjuvants, Anesthesia↗
PubMed1996

Microbial elicitors and their receptors in plants.

Elicitors are molecules that stimulate any of a number of defense responses in plants. Research over the past decade has focused on the mechanisms by which plant cells perceive and transduce these biological signals to activate defense responses. Of particular interest has been the identification of specific elicitor-binding proteins that might function as physiological receptors in the signal transduction cascade. The existence of specific high-affinity binding sites has been demonstrated for oligosaccharide, glycopeptide, and peptide elicitors, and candidate elicitor-binding proteins have been identified for several of them. The properties of these binding sites/proteins are consistent with those expected of physiologically important receptors, although experimental verification of the role of these binding proteins as receptors has not yet been obtained. The purification and characterization of specific elicitor-binding proteins is essential for a detailed understanding of the molecular basis for the signal exchange between plant hosts and microbial pathogens that leads to activation of host defenses.

Journal Article↗
PubMed1994

Data management for toxicological studies.

Organized data management increases the reliability of statistical analysis. The basic purpose of data management is to assure the integrity and the quality of data. To assure data validity, establishing a checking system, such as data audit, would be desirable at the following points: protocol design, supervision of study schedule, definition of data, data collection, choice of tests and procedures, verification, data checking, data recording, data handling, data analysis, and data validation. To process an enormous amount of data on a multitude of items, use of a computerized system would be advantageous. The data processing system in toxicological studies should be based on a protocol-driven system, which gathers and records the data accurately. The main functions that are to be handled by computer are data collection, recording and retrieval via terminals, and statistical analysis of data and assembling of reports. One should be able to validate whether the computer system would perform its intended function accurately, reliably, and consistently. This paper discusses the basic considerations of data management and provides examples of the state of the computerized data management system and its validation.

Animals↗
PubMed2004

Component dorsal hump reduction: the importance of maintaining dorsal aesthetic lines in rhinoplasty.

Dorsal hump reduction can create both functional and aesthetic problems if performed incorrectly. Component dorsal hump reduction allows a graduated approach to the correction of the nasal dorsum by emphasizing the integrity of the upper lateral cartilages when performing dorsal reduction. Use of this approach can minimize the need for spreader grafts in primary rhinoplasty patients. Possible untoward sequelae of dorsal hump reduction include long-term dorsal irregularities caused by uneven resection or overresection or underresection of the osseocartilaginous hump irregularity; the inverted-V deformity; and excessive narrowing of the midvault. The component dorsal hump reduction technique is a five-step method: (1) separation of the upper lateral cartilages from the septum, (2) incremental reduction of the septum proper, (3) dorsal bony reduction, (4) verification by palpation, and (5) final modifications (spreader grafts, suturing techniques, osteotomies). A graduated approach is described that offers control and precision at each interval. Fundamental to the final outcome is the protection and formation of strong dorsal aesthetic lines that define the appearance of the dorsum on frontal view. Furthermore, preservation of the transverse portions of the upper lateral cartilages is essential to maintain patency of the internal nasal valve, maintain the shape of the dorsal aesthetic lines, and avoid the inverted-V deformity. Finally, if needed, spreader grafts are enormously adaptable and can be customized for any deformity (unilateral or bilateral, visible or invisible) to handle functional or aesthetic problems.

Adult↗
PubMed1998

[The influence of acute hypercapnia on the permeability of the blood-brain barrier for gentamycin under conditions of general anesthesia in rabbits].

UNLABELLED: The aim of the work was to demonstrate whether acute hypercapnia (paCO2 > 65 mm Hg) influenced the permeability of blood-brain barrier (BBB). Twelve Chinchilla rabbits which underwent general anaesthesia were randomly divided into 2 groups. The animals were sedated with intravenous administration of pentobarbital, then were subjected to endotracheal intubation and connected to volume-controlled respirator (Zimmermann pump). Artificial ventilation using air/oxygen mixture was applied. Auricular artery, inferior caval vein and aorta were catheterized with a catheter being also placed in the lateral ventricle of the brain. General anaesthesia was supported with continuous intravenous administration of pentobarbital. To maintain normal paCO2 values, the investigation was performed under normal ventilation in control group (5 rabbits). Controlled hypoventilation was applied to achieve an increase of paCO2 in the shortest possible time in the investigated group (7 rabbits). Heart rate (HR), systolic (SAP), diastolic (DAP) and mean (MAP) arterial blood pressure, intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were continuously recorded. Gentamycin was applied as the marker of function of BBB, because it couldn't penetrate into the cerebrospinal fluid after intravenous administration under physiological conditions. BBB function in normal and significantly increased paCO2 was evaluated using gentamycin permeability indexes (QG), defined as gentamycin concentration ratio in the cerebrospinal fluid to serum gentamycin concentration in the same moment of trial. Comparative analysis of the QG index for both groups according to values achieved before the trial and after 1 and 3 hours of experiment indicates the degree of BBB damage. Non-parametric differences significance test according to Kolmogorow-Smirnow was applied for statistical verification of the results. Significance level for the trial was alpha = 0.05. RESULTS: None of the monitored parameters has changed in the control group. In the group of hypoventilated animals paCO2 values significantly statistically increased and pH values decreased after 1, 2 and 3 hours of the experiment (Fig. 1). In the investigated group increasing paCO2 values were followed by increase of ICP values, which became statistically significant during the third hour of hypercapnia. No statistically significant changes of the CPP values between animals from the control and investigated groups have been noticed. While comparing mean values of the gentamycin permeability index for the investigated group a minimal, statistically insignificant increase of the indexes has been stated during the first hour of hypercapnia. Continuous severe hypercapnia during next two hours caused increase of mean QG value of over 130% (Tab. 1, Fig. 2). That increase remained statistically insignificant as compared to the initial value and also to the estimated one after the first hour of hypercapnia. While comparing QG indexes between control and investigated groups in the given moments of trial it has been stated that mean QG value is statistically significantly higher in animals hypoventilated for 3 hours than in animals which experienced normal ventilation during the whole experiment. CONCLUSIONS: 1. Acute, severe hypercapnia disturbs the function of the blood-brain barrier for gentamycin. 2. For paCO2 values higher than 65 mm Hg no distinct relation between continuous increase of hypercapnia and functional status of blood-brain barrier has been found. 3. Evaluation of the blood-brain barrier function is a new and effective method for gentamycin application.

Acute Disease↗