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Biomedical subjects

F Gosselin

Publications and source records attributed to F Gosselin.

At least 19 recordsLinked to original sources

Sigma smooth pursuit eye tracking: constant k values revisited.

Effective sigma tracking, i.e., apparent movement perception when slow eye movements are made across a stationary repetitive pattern under stroboscopic illumination, has been shown to be a function of the distance between sequential stimuli (P(s)) and the flash frequency (f(s)). The relationship between these factors and eye velocity ( V (e)) has been formally specified as V (e)= k P(s)f(s)[deg s(-1)], where it has been argued that the value of k, which defines the rate limit for eye velocity, is normally 1, or exceptionally 2 or 3. However, theoretically the limitations on the maximum value for k are the maximum optimal pursuit speed for eye tracking (V(max)) and the minimum values which P(s) and f(s) can assume while preserving target discrimination, and since the values for V(max) are known to lie well beyond 20 deg/s and those for P(s) and f s) well below 0.3 deg and 10 Hz respectively, it should be possible to demonstrate empirically that k can assume integer values considerably larger than the indicated maximum of 3. To test this prediction, three subjects performed seven series of five EOG-monitored trials producing sigma-pursuit, with values of k ranging from 1 to 7. All subjects evidenced smooth pursuit eye tracking for every condition and reported experiencing sigma-type apparent motion in 95% of the trials. The results confirm theoretical expectations and unequivocally demonstrate that sigma tracking can be readily effected under conditions where k significantly exceeds the maximal values previously reported, in conformity with theory.

Adolescent↗

Asymmetric synthesis of the tricyclic core of NGF-inducing cyathane diterpenes via a transition-metal-catalyzed [5 + 2] cycloaddition.

[reaction: see text] A concise asymmetric synthesis of the tricyclic core of cyathane diterpenes is described, based on a novel transition-metal-catalyzed intramolecular [5 + 2] cycloaddition of ynone-vinylcyclopropane 10 (assembled from commercially available (S)-(-)-limonene), which proceeds in 90% yield with >95% selectivity. This strategy provides efficient access (14 steps and 13% overall yield) to potential analogues as well as precursors of nerve growth factor (NGF)-inducing diterpenes.

Cyclohexenes↗

Bubbles: a technique to reveal the use of information in recognition tasks.

Everyday, people flexibly perform different categorizations of common faces, objects and scenes. Intuition and scattered evidence suggest that these categorizations require the use of different visual information from the input. However, there is no unifying method, based on the categorization performance of subjects, that can isolate the information used. To this end, we developed Bubbles, a general technique that can assign the credit of human categorization performance to specific visual information. To illustrate the technique, we applied Bubbles on three categorization tasks (gender, expressive or not and identity) on the same set of faces, with human and ideal observers to compare the features they used.

Facial Expression↗

Why do we SLIP to the basic level? Computational constraints and their implementation.

The authors introduce a new measure of basic-level performance (strategy length and internal practicability; SLIP). SLIP implements 2 computational constraints on the organization of categories in a taxonomy: the minimum number of feature tests required to place the input in a category (strategy length) and the ease with which these tests are performed (internal practicability). The predictive power of SLIP is compared with that of 4 other basic-level measures: context model, category feature possession, category utility, and compression measure, drawing data from other empirical work, and 3 new experiments testing the validity of the computational constraints of SLIP using computer-synthesized 3-dimensional artificial objects.

Adult↗

Probing opioid receptor-ligand interactions by employment of indolizidin-9-one amino acid as a constrained Gly(2)-Gly(3) surrogate in a leucine-enkephalin mimic.

The relationship between the conformation and biological activity of Leu-enkephalin was studied using (2S,6R,8S)-9-oxo-8-N-(Boc)amino-1-azabicyclo[4.3.0]nonane-2-carboxylic acid [(2S,6R,8S)-1, I(9)AA] as a constrained Gly(2)-Gly(3) dipeptide surrogate. [I(9)AA](2,3)-Leu-enkephalin 12 was assembled using solid-phase peptide synthesis on Merrifield resin with TBTU as the coupling reagent. The in vitro assays indicated that [I(9)AA](2,3)-Leu-enkephalin 12 exhibited affinities for the mu- and delta-opioid receptors that were three orders of magnitude lower than that of Leu-enkephalin, as well as partial agonist character for both receptors. In in vivo assays for spinal analgesia, the indolizidinone analog 12 showed significantly enhanced duration of action, indicating an increased metabolic stability. Conformational analysis was performed using NMR and CD spectroscopy. The amide temperature coefficients and 3J(NH-CalphaH) coupling constants for 12 could not support a hydrogen-bonded beta-turn structure; however, its CD spectrum indicated a turn conformation. Incorporation of indolizidinone amino acid 1 into Leu-enkephalin thus provided additional support for the importance of a turn conformation for the biological activity of the native peptide.

Amino Acids↗

Rigid dipeptide surrogates: syntheses of enantiopure quinolizidinone and pyrroloazepinone amino acids from a common diaminodicarboxylate precursor.

A versatile and practical approach for synthesizing azabicyclo[X.Y.0]alkane amino acids of different ring sizes from a common diaminodicarboxylate precursor has been developed as a means for mimicking different peptide conformations. (2S,9S)-1-tert-Butyl 10-benzyl 5-oxo-2-[N-(PhF)amino] 9-[N-(BOC)amino]dec-4-enedioate (18) was first prepared in 83% yield by the Horner-Wadsworth-Emmons olefination of N-(PhF)aspartate beta-aldehyde 8 with pyroglutamate-derived beta-keto phosphonate 12 (PhF = 9-phenylfluoren-9-yl). The practicality of this approach for making azabicyclo[X.Y.0]alkane amino acids was then illustrated by the first synthesis of enantiopure quinolizidin-2-one amino acid 6 in seven steps and 40% overall yield from L-pyroglutamic acid. Hydrogenation of delta-keto alpha,omega-diaminosebacate 18, followed by lactam cyclization and protection, gave quinolizidin-2-one amino acid 6 as a single diastereomer. The versatility of this approach was next demonstrated by the synthesis of both ring-fusion isomers of pyrroloazepin-2-one amino acid 6 in 11 steps and 13% overall yield from pyroglutamic acid. Hydride reduction of 18, followed by methanesulfonate displacement, gave 5-alkylproline 22. Protective group manipulations, lactam cyclization, and removal of the ester group afforded readily separable pyrroloazepinone amino acids (7S)- and (7R)-7 in a 1:2 diastereomeric ratio. By introducing two new azabicycloalkane amino acids using our olefination approach, we have expanded the diversity of these important heterocycles for studying the conformational requirements for peptide biological activity.

Amino Acids↗

Design, synthesis, and conformational analysis of azacycloalkane amino acids as conformationally constrained probes for mimicry of peptide secondary structures.

Conformationally constrained amino acid and dipeptide units can serve in mimics of specific secondary structures for studying relationships between peptide conformation and biological activity. A variety of mimics are required to study systematically the structure-activity relationships in biologically relevant peptides. We present our efforts on the design, synthesis, and conformational analysis of a series of rigid surrogates of amino acid and dipeptide units for application within constrained peptide analogues, and for employment as inputs for combinatorial science. Conceived to be general and versatile, our methodology has delivered a variety of azacycloalkane and azabicycloalkane amino acids in enantiomerically pure form, via practical methods, from readily available and inexpensive starting materials.

Amino Acids↗

Prenatal diagnosis of congenital cytomegalovirus infection: prospective study of 237 pregnancies at risk.

OBJECTIVE: To develop recommendations for prenatal diagnosis of congenital cytomegalovirus (CMV) infection and evaluate possible prognostic markers. METHODS: We studied 237 pregnant women who had suspected or confirmed primary CMV infections by amniocenteses with or without funipuncture. Diagnosis of CMV was based on culture and polymerase chain reaction (PCR) done on amniotic fluid (AF) samples; fetal blood tests for CMV immunoglobulin M antibodies, PCR, and nonspecific biologic markers; and repeated ultrasound examinations. In cases of pregnancy termination, viral and pathologic examinations of fetuses were done. At birth, CMV infections were sought in newborns. Pediatric follow-up was scheduled for at least 2 years. RESULTS: Of 210 fetuses and newborns correctly evaluated, 55 had CMV infections. Ten of 38 fetuses infected before 20 weeks' pregnancy had severe congenital disease. The global sensitivity of prenatal diagnosis was 80%. Best sensitivity and 100% specificity were achieved by PCR done on AF sampled after 21 weeks' gestation, respecting a mean interval of 7 weeks between diagnosis of maternal infection and prenatal diagnosis. Fetal thrombocytopenia was associated with severe fetal disease. Ultrasound follow-up missed two fetuses who presented with neurologic impairment due to CMV after birth. CONCLUSION: A reliable prenatal diagnosis of congenital CMV infection based on PCR on amniocentesis samples can be made after 21 weeks' pregnancy, after a 7-week interval between diagnosis of maternal infection and antenatal procedure. Ultrasound and nonspecific biologic parameters are not sufficient to identify all fetuses at risk of severe sequelae.

Biomarkers↗

Test of mathematical assumptions behind the 'incidence function' estimation process of metapopulations' dynamic parameters.

I question Hanski's [I. Hanski, A practical model of metapopulation dynamics, J. Animal Ecol. 63 (1994) 151] assumption that incidence functions are relevant approximations of the equilibrium dynamics of stochastic metapopulation models to estimate models' parameters based on snapshot data. Based on ten different metapopulation models, this assumption is found to be at least partly unjustified when referring to the asymptotic behaviour of the models. This leads me to recommend the use of explicit extinction-colonisation transition probabilities and process data (rather than snapshot data) in the estimation process of metapopulation models.

Animals↗

Using the full power of linkage analysis in 11 French Canadian families to fine map the oculopharyngeal muscular dystrophy gene.

Oculopharyngeal muscular dystrophy (OPMD) is a late onset autosomal dominant muscular dystrophy with a high prevalence in the French Canadian population. We report linkage analysis with 7 chromosome 14q polymorphic markers in 11 large French Canadian families. An observed recombination in one family establishes D14S283 as the new centromeric flanking marker, therefore reducing the previously reported candidate interval from 5cM to 2cM. The highest two-point LOD score was 26.05 at theta = 0.01 for MYH7.1. Multipoint analysis suggested that the OPMD genes lies within a 1.5cM region around D14S990. This study of large French Canadian families underlines the great power of this population to fine map disease genes.

Adult↗

Motion-blur illusions.

The still-radii illusion, the figure-of-eight illusion, the band-of-heightened-intensity illusion and the dark-blurred-concentric-circles illusion have remained, until now, isolated relatively ill-explained phenomena. A single algorithmic model is proposed which explains these four visual illusions. In fact, this model predicts phenomena produced by motion of any gray-shaded patterns relative to the eyes (termed 'motion-blur illusions'). Results of a computer simulation of the model are presented. A novel instance of the proposed class of illusions, which can be readily experienced by the reader, is introduced to illustrate the generality of the model.

Computer Simulation↗

Friedreich ataxia in Acadian families from eastern Canada: clinical diversity with conserved haplotypes.

The gene for Friedreich ataxia (FRDA), an autosomal-recessive neurodegenerative disease, remains elusive. The current candidate region of about 150 kb lies between loci FR2 and F8101 near the D9S15/D9S5 linkage group at 9q13-21.1. Linkage homogeneity between classical FRDA and a milder, slowly progressive Acadian variant (FRDA-Acad) has been demonstrated. An extended D9S15-D9S5 haplotype (C6) predominates in FRDA-Acad chromosomes from Louisiana. We studied 10 Acadian families from New Brunswick, Canada. In eight families, affected individuals conformed to the clinical description of FRDA-Acad; in one, 2 sibs presented with spastic ataxia (SPA-Acad). In the last family, 2 sibs had FRDA-Acad, and one had SPA-Acad. We found that SPA-Acad is linked to the FRDA gene region. The C6 haplotype and a second major haplotype (B7) were identified. The same ataxia-linked haplotypes segregated with both FRDA-Acad and SPA-Acad in two unrelated families. The parental origins of these haplotypes were different. Our observation of different phenotypes associated with the same combination of haplotypes may point to the influence of the parent of origin on gene expression, indicate the effect of modifier genes, or reflect the presence of different mutations on the same haplotypes. Our findings underline the need to investigate families with autosomal-recessive ataxias for linkage to the FRDA region, despite lack of key diagnostic manifestations such as cardiomyopathy or absent deep-tendon reflexes.

Canada↗

Evaluation of commercial antisera for Shigella serogrouping.

Shigella serogrouping antisera from six companies (Becton Dickinson, Denka, Difco, Murex, Roach, and Sanofi-Pasteur) intended for the slide agglutination test and those of the Wellcolex Colour Shigella latex agglutination test were evaluated to identify quality products for Shigella identification. Forty-six reference Shigella strains (one for each serotype and species), 50 clinical strains (21 S. flexneri, 21 S. sonnei, 4 S. dysenteriae, 4 S. boydii) representing the most prevalent species and serotypes encountered in Quebec, and 9 non-Shigella strains were tested according to the manufacturers' instructions. A 3+ reaction (> or = 75% agglutination) was considered positive for the slide agglutination tests. Sensitivity varied from 47% (Roach) to 94% (Difco). For the 105 strains tested, accuracy ranged from 53% (Roach) to 91% (Wellcolex). Specificity varied from 97 to 100% for group A antisera, from 96 to 100% for group B antisera, from 88 to 100% for group C antisera, and from 95 to 99% for group D antisera. The costs of reagents required to test one strain varied from $3.50 to $13.20 (in Canadian dollars). In conclusion, Roach reagents proved to be unsatisfactory for Shigella serogrouping. Among those from the remaining companies, the Denka, Difco, and Wellcolex reagents met a performance standard of 90% accuracy.

Agglutination Tests↗

Red blood cell Cu/Zn superoxide dismutase activity in sporadic amyotrophic lateral sclerosis.

To determine the possible role of Cu/Zn superoxide dismutase (SOD1) in the pathophysiology of sporadic amyotrophic lateral sclerosis (SALS), we measured SOD1 activity in red blood cell lysates in patients with SALS. SOD1 activity in red blood cell lysates was independent of age and sex in control patients, and no significant difference was found between the levels of SOD1 activity in controls (1174.8 +/- 213, n = 29) and SALS patients (1203.4 +/- 214, n = 27). These results suggest that point mutations in the SOD1 gene are apparently unrelated to SALS.

Adult↗

[Fetomaternal alloimmunization: role of cordocentesis].

Twenty one pregnancies complicated by alloimmunization were managed by the use of intravascular method on an outpatient basis. One group was made of 9 women having had at least one pregnancy with a severely affected fetus. The other group was composed of 12 women without a previously affected infant; in 5 cases a situation at risk, either a transfusion (4 cases) or a severe obstetrical hemorrhage (1 case), was evidenced. Knowledge of fetal blood type (2 cases) and hematocrit determination obtained by fetal blood sampling allowed treatment individualized to the specific needs of each patient. In total 59 cordocenteses were performed, including 19 intrauterine transfusions.

Blood Transfusion, Intrauterine↗