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PubMed1978

[Highly different values for the plausibility of fatherhood and for the exclusion chance (author's transl)].

More than 1800 HLA-typed mother-child-putative father triplets were biostatistically analyzed on the basis of the Essen-Möller principle. 14 of them had W-values (= probability of paternity) of less than 50%, the lowest value being 4,4%. Using a specially designed computer program, exclusion probabilities between 68 and 96% were calculated. This demonstrates (a) that nonexclusion is not necessarily in every case a positive indication of the paternity of the man involved; and (b) that the probability of exclusion as a biological method of establishing paternity is not a suitable piece of evidence. The W-value (= "probability of paternity"), obtained on the basis of the Essen-Möller principle, provides complete information, and is alone conclusive.--The high proportion of non-fullhouse children among the 14 cases allows the conclusion that the more comprehensive the specificity spectrum of the antiserums used in the typing is, the fewer the number of such cases.

Blood Group Antigens↗

PubMed1992

Rapid molecular characterization of mutations leading to unstable hemoglobin beta-chain variants.

Characterization of unstable hemoglobins by protein analysis is often difficult. However, it is facilitated by DNA analysis, especially in the case of hyperunstable beta-chain variants, which produce a beta-thalassemia phenotype. We have applied an efficient strategy to the detection of such variants at the DNA level, based on computer-designed denaturing gradient gel electrophoresis (DGGE) of amplified DNA fragments. This approach makes it possible to detect any anomaly in the beta-globin gene. We describe the use of the DGGE method for rapid characterization of beta-chain variants and report a new missense mutation in the beta-globin gene third exon, beta 127 CAG-CGG/Gln-Arg, which is responsible for the synthesis of a highly unstable hemoglobin.

Adolescent↗

PubMedDate not supplied

Ethanol's influence on the stimulus level required to evoke an orienting response in goldfish.

In goldfish the heart rate orienting response to periodic photic stimuli was measured by a specially designed computer that also regulated the intensity of the stimuli to maintain the response. When ethanol was administered, the fish then exhibited orienting responses to less intense stimuli; this increased excitability was maintained for the duration of all tests (i.e., a maximum of 26 hours). There also seemed to be a residual increase of excitability lasting as long as 7 days after the ethanol was administered.

Animals↗

PubMed2006

MHC-BPS: MHC-binder prediction server for identifying peptides of flexible lengths from sequence-derived physicochemical properties.

Major histocompatibility complex (MHC)-binding peptides are essential for antigen recognition by T-cell receptors and are being explored for vaccine design. Computational methods have been developed for predicting MHC-binding peptides of fixed lengths, based on the training of relatively few non-binders. It is desirable to introduce methods applicable for peptides of flexible lengths and trained by using more diverse sets of non-binders. MHC-BPS is a web-based MHC-binder prediction server that uses support vector machines for predicting peptide binders of flexible lengths for 18 MHC class I and 12 class II alleles from sequence-derived physicochemical properties, which were trained by using 4,208 approximately 3,252 binders and 234,333 approximately 168,793 non-binders, and evaluated by an independent set of 545 approximately 476 binders and 110,564 approximately 84,430 non-binders. The binder prediction accuracies are 86 approximately 99% for 25 and 70 approximately 80% for five alleles, and the non-binder accuracies are 96 approximately 99% for 30 alleles. A screening of HIV-1 genome identifies 0.01 approximately 5% and 5 approximately 8% of the constituent peptides as binders for 24 and 6 alleles, respectively, including 75 approximately 100% of the known epitopes. This method correctly predicts 73.3% of the 15 newly published epitopes in the last 4 months of 2005. MHC-BPS is available at http://bidd.cz3.nus.edu.sg/mhc/ .

Algorithms↗

PubMed1970

The ergonomics laboratory, E.M.I. Electronics Ltd.

The origins of the Ergonomics Laboratory within EMI Electronics are outlined and milestones in its development discussed. Reference is made to important contributions to the growth of ergonomics in areas including research, consumer goods, equipment design, system design, computers, training and military work. A selected bibliography of the more significant published work is included.

Journal Article↗

PubMed1991

Sensory neurons of the rat sciatic nerve.

Experiments have been undertaken in this laboratory over recent years to accurately determine the numbers and sizes of somatic neurons which contribute to the normal sciatic nerve, at mid-thigh levels, of the adult, albino rat. This article is concerned with the dorsal root ganglion (DRG) neuron population of the sciatic nerve whose cell bodies were identified through retrograde labeling of cut branches of the sciatic with horseradish peroxidase (HRP) and/or its wheat germ conjugate (WGA-HRP). It is essential to understand the neuronal composition of the normal rat sciatic nerve if the consequences of aging, nerve injury, and surgical repair to improve functional regeneration are to be properly evaluated. Neuron counts were determined from camera-lucida paper drawings of all labeled profiles in DRGs L3-L6 at 100 x magnification. The profiles, obtained by labeling individual branches of the sciatic nerve (sural, lateral sural, tibial, peroneal, medial, and lateral gastrocnemius/soleus nerves) were traced from 40-microns-thick, serial, frozen sections. The sizes of the perikarya, areas and diameters, were determined by tracing the perimeters of the drawn profiles on a digitizing tablet. The tablet's output was inputted directly into a specially designed computer spreadsheet which contained a mathematical table for correcting the split-cell error inherent to the sectioning process. Afferents from any given branch of the sciatic normally occupied two to three adjacent ganglia. Sciatic DRG neurons were normally located in lumbar ganglia L3-L6. Nearly 98-99% of all sciatic DRG perikarya resided in the L4 and L5 DRGs. The L6 DRG, traditionally regarded as an important contributor to the rat sciatic, contained merely 0.4% of its afferent neurons while the L3 ganglion, frequently overlooked as a contributor, contained 1.2% of the mid-thigh sciatic afferents. The mean size of rat DRG neurons was about 29 microns (550-600 microns2). The corrected counts revealed that the normal sciatic nerve (at mid-thigh levels), in rats between 2 and 12 months of age, contained a mean, total DRG neuron population of about 10,500 neurons. This is probably an underestimate by 3-5% of the true number due to occasional unreliable labeling of some of the small DRG neurons. It is estimated that the normal, mean number of sciatic DRG neurons of young to middle-aged rats lies somewhere between 10,500 and 11,000 +/- 2000. The data suggest that nearly 20% of all DRG neurons in the sciatic nerve supply muscle afferents. The vast majority of the remaining neurons are involved with innervation of the skin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Failure mechanisms at the human dentin-resin interface: a fracture mechanics approach.

The present study reports on the failure mechanisms at the human dentin-resin interface, with special reference to two specific questions: (1) does failure at the human dentin-resin interface occur by a cohesive or an adhesive mechanism? (2) is the failure mechanism accompanied by a plastic deformation, and if so how important is it? The experimental design, computational analysis, and fractography were applied to two generically different bonding systems: Scotchbond-2 (SB2) and Scotchbond-multipurpose (SBM). The theoretical basis of the study required a three-dimensional finite element analysis for calibration of the new geometric factor coefficient. A minimum geometric factor coefficient (Ym) of 17.3 was then obtained which was vital for the determination of the interfacial fracture toughness. Accordingly, the dentin-resin interfacial fracture toughness (GIC), for the SB2 and for the SBM were 30.22 +/- 5.61 and 49.56 +/- 7.65 J m-2, respectively, which were significantly different (p < 0.01). Both SB2 and SBM interfaces with dentin displayed significant degrees of plasticity (0.15 and 0.19) which were beneficial to crack resistance. Thus, correcting for the plasticity, the GIC for SB2 and for SBM increased to 42.83 +/- 7.75 and 74.97 +/- 10.47 J m-2, respectively. The fractography of the two systems reflected these numeric differences. SB2 showed largely interfacial adhesive failure, while SBM showed adhesive-cohesive failure with occasional dentin adhesions attached to the composite interface and vice versa.

Adhesiveness↗

PubMed1984

Left ventricular wall motion: its dynamic transmural characteristics.

Cardiac wall motion has been studied extensively. It is usually determined by indirect two-dimensional measurements for the true three-dimensional (3D) motion with its specific speed and direction. Errors are also introduced by using internally fixed reference systems and by the inability to identify precise points on the heart wall during the cardiac cycle. Because of these limitations, the endocardial and epicardial wall motion and their relationship are still unclear. This study was designed to assess endocardial and epicardial wall motion by measuring the direction and speed of implanted markers in an externally fixed 3D coordinate system. Fifty-seven pairs of endocardial and epicardial metallic markers were placed at anterior, lateral, posterior, basal, and apical regions of the left ventricles of 14 normal mongrel dogs. Biplane cineradiographs were performed at 50 frames/sec, and the 3D motions of the markers were analyzed using a specially designed computer system. It was found that the speeds, directions, displacements, and phases of the movements of corresponding endocardial and epicardial points were highly correlated. The correlation coefficients were 0.77 to 0.95 for the mean directions, 0.61 to 0.96 for the mean speeds, and 0.59 to 0.96 for the mean displacements at various regions of the heart, and the periodic movements of the endocardium and epicardium were always in phase. The mean epicardial speeds and displacements are fixed proportions (approximately 70%) of the mean endocardial speeds and displacements despite the differences in absolute values between regions in the same dog and the same regions in different dogs. The correlation coefficients for endocardial and epicardial instantaneous speeds, directions, and velocities ranged from 0.68 to 0.83, 0.81 to 0.88, and 0.77 to 0.86, respectively, for different regions of the heart. The correlation coefficients were significant for both the mean values and the instantaneous values. Thus, when only fixed epicardial points are accessible for wall motion measurements in clinical situations, it is possible to infer the endocardial motion from the epicardial motion.

Animals↗

PubMed1991

Cellular and subcellular redistribution of glutamate-, glutamine- and taurine-like immunoreactivities during forebrain ischemia: a semiquantitative electron microscopic study in rat hippocampus.

The effect of 20 min of ischemia on the cellular and subcellular distribution of glutamate, glutamine and taurine in the rat hippocampus was studied by means of an immunocytochemical procedure based on antisera raised against protein glutaraldehyde conjugates of the respective amino acids. Forebrain ischemia was induced by temporary occlusion of the common carotid arteries in rats with permanently occluded vertebral arteries. Within 90 s after removal of the carotid ligatures, the rats were perfused through the heart with a mixture of glutaraldehyde and paraformaldehyde. For semiquantitative electron microscopic analysis, ultrathin sections were incubated in a primary antiserum followed by a secondary antibody coupled to colloidal gold particles. The gold particle densities over different tissue compartments within the CA1 field and the mossy fiber zone of the hippocampus were determined by means of a specially designed computer program, and values from normal and ischemic animals were compared. It was found that in the astrocytes, the level of immunoreactivity for glutamine and taurine is unchanged or slightly decreased after ischemia, while that for glutamate is increased, particularly within the mitochondria (by about 100%). In contrast, pyramidal cell bodies display a reduced immunolabeling for all three amino acids following the ischemic episode. The results show that ischemia causes a redistribution of glutamate from neurons to glia. The observed increase in the glial immunolabeling for glutamate indicates that the capacity of the glial cells to metabolize glutamate is exceeded during ischemia. This glial response to ischemia has not previously been recognized and may play a role in the chain of events leading to "excitotoxic" cell death during or following an ischemic episode. The reduction of glutamate and taurine immunolabeling in neurons points to a possible amino acid efflux and is compatible with previous biochemical studies demonstrating an elevated extracellular level of these amino acids during ischemia.

Animals↗

PubMed1984

Interstitial high dose-rate brachytherapy: principle, practice and first clinical experiences with a new remote-controlled afterloading system using Ir-192.

In our newly developed remote-controlled afterloading system, a single Ir-192-source is moved within hollow stainless steel needles, which are arranged strictly parallel and are uniformly spaced. Dose calculation is performed by an especially designed computer program using geometrical bodies (ellipsoid, cylinder and plane parallel body) as idealized tumor shapes. Reference points for calculation are defined on the surface of the chosen geometrical body. Theoretical base, principles of dosage, handling and first clinical experiences after treatment of 28 patients are presented.

Brachytherapy↗

PubMed1995

Novelty seeking behavior in the rat is dependent upon the integrity of the noradrenergic system.

These experiments were designed to investigate the role of the noradrenergic system in promoting investigation of novelty in rats. Behavior was monitored in a hole board equipped with photoelectric cells strategically placed so that locomotor activity, rearing and investigation of each of the holes could be quantified independently. Specially designed computer software permitted recording of the sequence and cumulative duration of the visits to specific holes throughout the session. Dose-response curves of the sedative effect of the alpha 2 adrenergic receptor agonist clonidine were established, a sedative effect being defined as a decrease in overall horizontal displacements, rearings and hole visits. After a one week interval, the rats were rerun in the holeboard, with novel objects placed in four of the nine holes. Previous experiments had shown that rats spend significantly more time investigating holes containing objects than empty holes in this apparatus and this was replicated here. Doses of clonidine which were below threshold for inducing any sedative effect (10 micrograms/kg) totally eliminated preference for holes with objects while having no effect on total time investigating the holes. A subsequent experiment showed that the beta receptor antagonist propranolol (10 mg/kg) produced a similar effect. These results suggest that the noradrenergic system is implicated in stimulus seeking behavior and the post-synaptic beta receptors are involved in mediating the behavior.

Adrenergic beta-2 Receptor Antagonists↗

PubMed1993

Inhibition of estrogen stimulated mitogenesis by 3-phenylacetylamino-2,6-piperidinedione and its para-hydroxy analog.

3-Phenylactetylamino-2,6-piperidinedione (A10) inhibited estradiol stimulated cell growth in the MCF-7 (E3) human breast tumor cell line in vivo and in vitro. While high concentrations of A10 were needed to inhibit cell proliferation (IC50 = 3 x 10(-3) M in vitro), the compound demonstrated little toxicity. The effect appeared specific since a hydrolysis product of A10, phenylacetylglutamine, demonstrated no growth inhibitory activity at similar concentrations in MCF-7 (E3) cells in vitro. A computer designed analog, p-hydroxy A10, was more potent than A10 in inhibiting activity in MCF-7 (E3) cells in vitro. The IC50 for p-hydroxy A10 was 7 x 10(-6) M which was comparable to that of the antiestrogen, tamoxifen (IC50 1 x 10(-7) M). All three compounds caused a decline in estrogen receptor levels in a dose-dependent fashion. A10 also inhibited estradiol induction of progesterone receptors. Examination of protein kinase activity following an acute exposure to a 10(-11) M growth stimulatory dose of estradiol revealed a 168% increase in protein kinase activity over that of untreated control cells. A10 in a dose-responsive fashion inhibited the estradiol stimulated increase in protein kinase activity. The protein kinase activity was also inhibited by p-hydroxy A10. These activities of A10 and p-hydroxy A10 coupled with the low toxicity and novelty of the basic A10 structure provide an exciting possibility of developing a new class of clinically useful antineoplastic drugs with minimal side effects.

Animals↗

PubMed2005

Non-stochastic and stochastic linear indices of the 'molecular pseudograph's atom adjacency matrix': application to 'in silico' studies for the rational discovery of new antimalarial compounds.

Malaria is one of the most deadly diseases, affecting million of people especially in developing countries. Because of the rapidly increasing threat worldwide of malaria epidemics multidrugs resistant to therapies, there is an urgent global need to discover new classes of antimalarial compounds. In an effort to overcome this problem, we have investigated the use of structure-based classification models for the 'rational' selection/identification or design/optimization of new lead antimalarials from virtual combinatorial data sets. In this sense, TOpological MOlecular COMputer Design strategy (TOMOCOMD approach) has been introduced in order to obtain two quantitative models for the discrimination of antimalarials. A collected data set containing 597 antimalarial compounds is presented as a helpful tool not only for theoretical chemist but for other researchers in this area. The validated models (including non-stochastic and stochastic indices) classify correctly more than 90% of compounds in both training and external prediction data sets. They showed high Matthews' correlation coefficients; 0.87 and 0.82 for training and 0.86 and 0.79 for test set. The TOMOCOMD-CARDD approach implemented in this work was successfully compared with two of the most useful models for antimalarials selection reported so far. Thus we expect that these two QSAR models can be used in the identification of previously un-known antimalarials compounds.

Antimalarials↗

PubMed2004

Synthesis of new fluoroquinolones and evaluation of their in vitro activity on Toxoplasma gondii and Plasmodium spp.

The synthesis of four new computer-designed fluoroquinolones which have been predicted by QSAR analysis to be active against the protozoa Toxoplasma gondii is described. These compounds are inhibitory in vitro for T. gondii. One of these compounds has a remarkably high activity comparable to that of trovafloxacin. It combines the basic cyclopropyl-quinoline structure of gatifloxacin or moxifloxacin with the C-7 6-amino-3-azabicyclo[3.1.0]hexyl side chain of trovafloxacin. The four compounds are also inhibitory for blood stages of Plasmodium falciparum though at high concentration. These results confirm the potential of quinolones as anti-T. gondii and antimalarial drugs but also show that the QSAR models for T. gondii cannot be reliably extended for screening antimalarial activity.

Animals↗

PubMed2006

Ca2+ indicators based on computationally redesigned calmodulin-peptide pairs.

The binding interface of calmodulin and a calmodulin binding peptide were reengineered by computationally designing complementary bumps and holes. This redesign led to the development of sensitive and specific pairs of mutant proteins used to sense Ca(2+) in a second generation of genetically encoded Ca(2+) indicators (cameleons). These cameleons are no longer perturbed by large excesses of native calmodulin, and they display Ca(2+) sensitivities tuned over a 100-fold range (0.6-160 microM). Incorporation of circularly permuted Venus in place of Citrine results in a 3- to 5-fold increase in the dynamic range. These redesigned cameleons show significant improvements over previous versions in the ability to monitor Ca(2+) in the cytoplasm as well as distinct subcellular localizations, such as the plasma membrane of neurons and the mitochondria.

Amino Acid Sequence↗

PubMed2006

Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants.

OBJECTIVE: The aim of this study was to examine the relationship between cortical development and cerebral electrical activity at early gestational ages. METHODS: We obtained EEGs (7.2+/-3.8 days) and MR brain images (3.2+/-2.9 days) after birth in 17<30 week gestation infants without evidence of focal brain injury The EEGs were assessed for discontinuity and characteristic maturational features (delta brush, occipital and temporal sawtooth); cortical development was quantified from MR scans using a specially designed computer programme to measure cortical folding. RESULTS: The inter-burst interval shortened and cortical folding increased with increasing post-menstrual age (PMA). In contrast, the minimum duration of bursts was independent of PMA and cortical folding. Delta brush (8-20 Hz activities) was seen at all PMAs; temporal and occipital sawtooth activities were always more prominent than delta brush but were seen less frequently with increasing PMA and complexity of cortical folding. CONCLUSION: There was a positive correlation between some but not all maturational features of the preterm neonatal EEG and the complexity of whole brain cortical folding and PMA. These relationships were strong for the inter-burst interval, a global measure of maturation, but not strongly seen for regional features such as occipital and temporal sawtooth within this gestational age range. SIGNIFICANCE: Combining neurophysiological examination with detailed neuroimaging gives insights into developmental changes occurring in the very preterm brains and suggests further comparative studies focusing on measures of focal brain development at different gestational ages.

Cerebral Cortex↗

PubMed2006

Factors influencing operation time of laparoscopy-assisted distal subtotal gastrectomy: analysis of consecutive 100 initial cases.

AIMS: There is little information on patient selection criteria for laparoscopy-assisted distal gastrectomy (LADG) that would facilitate a successful initial experience for a surgeon new to the procedure. This study aimed to establish patient selection criteria that will allow increased proficiency and shorter operation times for the LADG procedure. METHOD: One hundred LADG with lymphadenectomy and no other combined procedures were consecutively performed by one surgeon. These 100 consecutive LADG procedures were analyzed retrospectively from a prospectively designed computer database. Uni- and multivariate analyses were performed to identify factors influencing operation time. RESULTS: According to univariate analysis, operation time was influenced by sex, BMI, surgical experience, and tumor location, whereas multivariate analysis indicated that operation time was significantly influenced only by BMI and surgical experience. The same analyses of only the first 50 cases showed that sex, BMI, surgical experience, and tumor location were independently associated with operation time. As BMI increased, so did operation time, whereas operation time decreased with increasing surgical experience. CONCLUSION: This study suggests that surgeons who have limited experience with this advanced procedure may shorten operation time by considering patient and tumor characteristics in their early attempts at LADG. With a shortened operation time, surgeon with limited experience may become proficient to LADG rapidly.

Adult↗

PubMed2005

The problem of single parent/child paternity analysis--practical results involving 336 children and 348 unrelated men.

In a certain amount of paternity investigations, only DNA from child and alleged father is analyzed, thus increasing the possibility of false paternity inclusions. The aim of this study was to determine how many wrong paternity inclusions could be detected in a rather small geographical area comparing empirical results from 336 children and 348 men (13-15 STRs were investigated per person). This comparison between each child and all unrelated men (i.e. all putative fathers from the other cases) with an especially designed computer program resulted in 116,004 man/child pairs. Less than three excluding STRs were found in 1666 child/unrelated man pairs (1.44% of the comparisons). At least one unrelated man with only two or less STR mismatches could be determined for 322 children (95.8% of all investigated children). In 26 comparisons no STR mismatches between a child and an unrelated man were detected, thus at least one and up to three "second father(s)" under 350 men could be found for 23 children, if the mother is excluded. Paternity probabilities between 95.475% and 99.996% were calculated. Our results underline the difficulties in motherless paternity cases using only STR analysis and advise great precaution in assigning verbal predicates such as "paternity proven" in those investigations.

Adult↗