Showing papers by "Laval University published in 1995"

Heteronuclear decoupling in rotating solids

Abstract: A simple two pulse phase modulation (TPPM) scheme greatly reduces the residual linewidths arising from insufficient proton decoupling power in double resonance magic angle spinning (MAS) experiments. Optimization of pulse lengths and phases in the sequence produces substantial improvements in both the resolution and sensitivity of dilute spins (e.g., 13C) over a broad range of spinning speeds at high magnetic field. The theoretical complications introduced by large homo‐ and heteronuclear interactions among the spins, as well as the amplitude modulation imposed by MAS, are explored analytically and numerically. To our knowledge, this method is the first phase‐switched sequence to exhibit improvement over continuous‐wave (cw) decoupling in a strongly coupled homogeneous spin system undergoing sample spinning.

Potential theory in the complex plane

Abstract: Potential theory is the broad area of mathematical analysis encompassing such topics as harmonic and subharmonic functions, the Dirichlet problem, harmonic measure, Green's functions, potentials and capacity. This is an introduction to the subject suitable for beginning graduate students, concentrating on the important case of two dimensions. This permits a simpler treatment than other books, yet is still sufficient for a wide range of applications to complex analysis; these include Picard's theorem, the Phragmen–Lindelof principle, the Koebe one-quarter mapping theorem and a sharp quantitative form of Runge's theorem. In addition there is a chapter on connections with functional analysis and dynamical systems, which shows how the theory can be applied to other parts of mathematics, and gives a flavour of some recent research. Exercises are provided throughout, enabling the book to be used with advanced courses on complex analysis or potential theory.

A semiparametric estimation procedure of dependence parameters in multivariate families of distributions

Abstract: SUMMARY This paper investigates the properties of a semiparametric method for estimating the dependence parameters in a family of multivariate distributions. The proposed estimator, obtained as a solution of a pseudo-likelihood equation, is shown to be consistent, asymptotically normal and fully efficient at independence. A natural estimator of its asymptotic variance is proved to be consistent. Comparisons are made with alternative semiparametric estimators in the special case of Clayton's model for association in bivariate data.

The Molecular Basis of Turcot's Syndrome

Abstract: Background Turcot's syndrome is characterized clinically by the concurrence of a primary brain tumor and multiple colorectal adenomas. We attempted to define the syndrome at the molecular level. Methods Fourteen families with Turcot's syndrome identified in two registries and the family originally described by Turcot and colleagues were studied. Germ-line mutations in the adenomatous polyposis coli (APC) gene characteristic of familial adenomatous polyposis were evaluated, as well as DNA replication errors and germ-line mutations in nucleotide mismatch-repair genes characteristic of hereditary nonpolyposis colorectal cancer. In addition, a formal risk analysis for brain tumors in familial adenomatous polyposis was performed with a registry data base. Results Genetic abnormalities were identified in 13 of the 14 registry families. Germ-line APC mutations were detected in 10. The predominant brain tumor in these 10 families was medulloblastoma (11 of 14 patients, or 79 percent), and the relative risk of cer...

PCR mapping of integrons reveals several novel combinations of resistance genes.

Abstract: The integron is a new type of mobile element which has evolved by a site-specific recombinational mechanism. Integrons consist of two conserved segments of DNA separated by a variable region containing one or more genes integrated as cassettes. Oligonucleotide probes specific for the conserved segments have revealed that integrons are widespread in recently isolated clinical bacteria. Also, by using oligonucleotide probes for several antibiotic resistance genes, we have found novel combinations of resistance genes in these strains. By using PCR, we have determined the content and order of the resistance genes inserted between the conserved segments in the integrons of these clinical isolates. PCR mapping of integrons can be a useful epidemiological tool to study the evolution of multiresistance plasmids and transposons and dissemination of antibiotic resistance genes.

Measuring System Usage: Implications for IS Theory Testing

Abstract: There is widespread agreement among researchers that system usage, defined as the utilization of information technology IT by individuals, groups, or organizations, is the primary variable through which IT affects white collar performance. Despite the number of studies targeted at explaining system usage, there are crucial differences in the way the variable has been conceptualized and operationalized. This wide variation of system usage measures hinders the efforts of MIS researchers to compare findings across studies, thus impeding the accumulation of knowledge and theory in this area. The purpose of this paper is to address conceptual as well as methodological issues related to measuring system usage. First, via LISREL measurement modeling techniques, we compare subjective and objective measures of system usage, namely, self-reported versus computer-recorded measures. Next, using a modified form of Davis' Technology Acceptance Model TAM as a nomological net, we test the nomological validity of these system usage constructs and measures. Results of the LISREL measurement and nomological net analysis suggest that system usage should be factored into self-reported system usage and computer-recorded system usage. Contrary to expectations, these constructs do not appear to be strongly related to each other. Moreover, while self-reported measures of system usage are related to self-reported measures of TAM independent variables, objective, computer-recorded measures show distinctly weaker links. In the face of such counter-evidence, it is tempting to argue that research that has relied on subjective measures of system usage for example, research confirming TAM may be artifactual. There are several alternative explanations, though, that maintain the integrity of TAM and studies that measure system usage subjectively. These alternative explanations suggest directions for further research as well as new approaches to measurement.

An STS-Based Map of the Human Genome

Abstract: A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorporated a genetic linkage map of the human genome containing 5264 loci. This information was combined with the results of STS-content screening of 10,850 loci against a yeast artificial chromosome library to produce an integrated map, anchored by the radiation hybrid and genetic maps. The map provides radiation hybrid coverage of 99 percent and physical coverage of 94 percent of the human genome. The map also represents an early step in an international project to generate a transcript map of the human genome, with more than 3235 expressed sequences localized. The STSs in the map provide a scaffold for initiating large-scale sequencing of the human genome.

The roles of social withdrawal, peer rejection, and victimization by peers in predicting loneliness and depressed mood in childhood

Abstract: The purpose of this study was to evaluate the relative contributions of social withdrawal, peer rejection, and victimization by peers in predicting feelings of loneliness and depressed mood over time. According to the proposed model, the feelings of loneliness associated with social withdrawal are mediated by the negative peer experiences (negative peer status and peer victimization) to which withdrawn children are exposed. In predicting depressed mood over time, it was further hypothesized that self-reported loneliness ultimately mediates the subsequent depressed mood associated with withdrawal and negative peer experiences. The study was conducted across 2 consecutive years (Time 1 and Time 2), with children each year nominating peers for peer status, social withdrawal, and victimization measures, and completing self-report measures of loneliness and depressed mood. Fourth- and fifth-grade children participated at Time 1, and children that remained in the same school were again evaluated at Time 2 (N = 567). A series of regression analyses indicated that the postulated sequence of mediations adequately represented the pattern of longitudinal associations between the variables, as well as their pattern of change over time. The contribution of social withdrawal to the prediction of subsequent loneliness was accounted for by the expected pattern of mediations of negative peer experiences. Self-reported loneliness ultimately mediated the subsequent depressed mood associated with withdrawal and negative peer experiences.

Cellular Basis of EEG Slow Rhythms: A Study of Dynamic Corticothalamic Relationships

Abstract: A slow oscillation (< 1 Hz) has recently been described in intracellular recordings from the neocortex and thalamus (Steriade et al., 1993c-e). The aim of the present study was to determine the phase relations between cortical and thalamic neuronal activities during the slow EEG oscillation. Intracellular recordings were performed in anesthetized cats from neurons in motor and somatosensory cortical areas, the rostrolateral sector of the reticular (RE) thalamic nucleus, and thalamocortical (TC) cells from ventrolateral (VL) nucleus. The EEG was used as time reference for alignment of activities in different, simultaneously recorded neurons, including dual impalements of cortical cells as well as cortical and TC cells. The spontaneous EEG oscillation was characterized by slowly recurring (0.3–0.9 Hz) sequences of surface- positive (depth-negative) sharp deflections, often followed by oscillatory activity within the frequency range of sleep spindles (7–14 Hz) or at faster frequencies. Cortical and RE cells were similarly hyperpolarized during the depth-positive EEG waves and were depolarized during the depth-negative EEG deflections. In many instances, the cell depolarization was associated with oscillations at the spindle frequency or with tonic firing at rates related to the level of depolarization. TC neurons were hyperpolarized during the depth- positive EEG waves and displayed a series of IPSPs, at the spindle frequencies, during the depth-negative EEG waves. Depending on the membrane potential (Vm), TC cells could fire spike bursts at the onset of the EEG depth-negativity, or their firing could be delayed by subsequent IPSPs. The sequence of spontaneous EEG and cellular events described above also characterized the responses to cortical and thalamic stimulation. Simultaneous intracellular recordings of pairs of cortical cells or cortical and TC cells showed that spontaneous transitions from less synchronized to more synchronized EEG states were marked by a simultaneous hyperpolarization, coincident with an overt depth-positive EEG wave. We conclude that during low-frequency oscillatory states, characteristic of slow-wave sleep, neocortical and thalamic neurons display phase relations that are restricted to narrow time windows, and that synchronization results from a generalized inhibitory phenomenon. Moreover, EEG synchronization is reflected as active inhibition in TC neurons. That this pattern is also present in states of hypersynchronization, such as seizure activity, is shown in the following paper (Steriade and Contreras, 1994).

Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27.

Abstract: Phosphorylation of heat shock protein 27 (HSP27) can modulate actinfilament dynamics in response to growth factors. During heat shock, HSP27 is phosphorylated at the same sites and by the same protein kinase as during mitogenic stimulation. This suggests that the same function of the protein may be activated during growth factor stimulation and the stress response. To determine the role of HSP27 phosphorylation in the heat shock response, several stable Chinese hamster cell lines that constitutively express various levels of the wild-type HSP27 (HU27 cells)oranonphosphorylatableformofhumanHSP27(HU27pm3cells)weredeveloped.IncontrasttoHU27cells, whichshowedincreasedsurvivalafterheatshock,HU27pm3cellsshowedonlyslightlyenhancedsurvival.Evidence is presented that stabilization of microfilaments is a major target of the protective function of HSP27. In the HU27pm3 cells, the microfilaments were thermosensitized compared with those in the control cells, whereas wild-typeHSP27causedanincreasedstabilityofthesestructuresinHU27cells.HU27butnotHU27pm3cellswere highly resistant to cytochalasin D treatment compared with control cells. Moreover, in cells treated with cytochalasin D, wild-type HSP27 but not the phosphorylated form of HSP27 accelerated the reappearance of actin filaments. The mutations in human HSP27 had no effect on heat shock-induced change in solubility and cellular localizationoftheprotein,indicatingthatphosphorylationwasnotinvolvedintheseprocesses.However,induction ofHSP27phosphorylationbystressingagentsormitogenscausedareductioninthemultimericsizeofthewild-type protein, an effect which was not observed with the mutant protein. We propose that early during stress, phosphorylation-induced conformational changes in the HSP27 oligomers regulate the activity of the protein at the level of microfilamentdynamics,resultinginbothenhancedstabilityandacceleratedrecoveryofthefilaments.Thelevelof protectionprovidedbyHSP27duringheatshockmaythusrepresentthecontributionofbettermaintenanceofactin filament integrity to overall cell survival.

Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution

Abstract: Although specific proteinases play a critical role in the active phase of apoptosis, their substrates are largely unknown. We previously identified poly(ADP-ribose) polymerase (PARP) as an apoptosis-associated substrate for proteinase(s) related to interleukin 1 beta-converting enzyme (ICE). Now we have used a cell-free system to characterize proteinase(s) that cleave the nuclear lamins during apoptosis. Lamin cleavage during apoptosis requires the action of a second ICE-like enyzme, which exhibits kinetics of cleavage and a profile of sensitivity to specific inhibitors that is distinct from the PARP proteinase. Thus, multiple ICE-like enzymes are required for apoptotic events in these cell-free extracts. Inhibition of the lamin proteinase with tosyllysine "chloromethyl ketone" blocks nuclear apoptosis prior to the packaging of condensed chromatin into apoptotic bodies. Under these conditions, the nuclear DNA is fully cleaved to a nucleosomal ladder. Our studies reveal that the lamin proteinase and the fragmentation nuclease function in independent parallel pathways during the final stages of apoptotic execution. Neither pathway alone is sufficient for completion of nuclear apoptosis. Instead, the various activities cooperate to drive the disassembly of the nucleus.

A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia

Abstract: The outcome of the first pilot study of liver-directed gene therapy is reported here. Five patients with homozygous familial hypercholesterolaemia (FH) ranging in age from 7 to 41 years were enrolled; each patient tolerated the procedure well without significant complications. Transgene expression was detected in a limited number of hepatocytes of liver tissue harvested four months after gene transfer from all five patients. Significant and prolonged reductions in low density lipoprotein (LDL) cholesterol were demonstrated in three of five patients; in vivo LDL catabolism was increased 53% following gene therapy in a receptor negative patient, who realized a reduction in serum LDL equal to ∼150 mg dl−1. This study demonstrates the feasibility of engrafting limited numbers of retrovirus-transduced hepatocytes without morbidity and achieving persistent gene expression lasting at least four months after gene therapy. The variable metabolic responses observed following low-level genetic reconstitution in the five patients studied precludes a broader application of liver-directed gene therapy without modifications that consistently effect substantially greater gene transfer.

Oocyte and follicular morphology as determining characteristics for developmental competence in bovine oocytes

Abstract: Follicular size, follicular atresia, and oocyte morphology were investigated for the possible relation of these characteristics to the developmental competence of bovine oocytes. Ovaries from a local slaughterhouse were dissected to obtain a heterogeneous population of follicles. Half of each follicle was fixed for histological analysis, and the oocytes were detached carefully and cultured individually. Before in vitro maturation, the oocytes were grouped into six different classes based on the morphology of the cumulus and the ooplasm: classes 1 and 2 represent oocytes with a homogeneous ooplasm plus a compact and complete cumulus, and classes 3-6 represent oocytes with a granulated ooplasm and an incomplete and/or expanded cumulus. Oocytes from class 3 (beginning of expansion in outer cumulus layers and slight granulations in the ooplasm) developed past the 16-cell stage significantly (P < 0.05) more than oocytes with a compact and complete cumulus (classes 1 and 2) and oocytes from classes 4-6 (incomplete and/or expanded cumulus) after 5 days of in vitro culture. Oocytes from follicles measuring 3 mm or less did not develop past the 16-cell stage, whereas follicles of 3-5 mm and 5 mm or larger developed at similar rates (17% and 21% morulae, respectively). The state of the follicle did not affect whether an embryo reached at least the 16-cell stage, as comparable rates were obtained in all three groups of follicles: nonatretic (20%), intermediate (14%), and slightly atretic (16%).(ABSTRACT TRUNCATED AT 250 WORDS)

Plankton and nutrient dynamics in marine waters

Abstract: Biological oceanographers generally distinguish between two contrasting trophic pathways in the pelagic environment, i.e. the herbivorous and the microbial food webs. The former goes from large phytoplankton and zooplankton to fish, whereas the latter comprises small eukaryotic algae and cyanobacteria as well as heterotrophic bacteria and protozoa. The present paper describes a continuum of trophic pathways, between systems dominated by the herbivorous food web and those dominated by the microbial loop (i.e. almost closed system of heterotrophic bacteria and zooflagel-late grazers, the latter releasing dissolved organic matter used as substrate by the bacteria). It is proposed that the continuum goes from the herbivorous web (or chain) to a “multivorous food web”, to the microbial web, and finally the microbial loop. Characteristics of the various pathways maybe summarized as a series of interconnected ratios. It is hypothesized that systems dominated by the herbivorous food web or the microbial ...

Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder.

Abstract: The disorder of autosomal dominant nocturnal frontal lobe epilepsy has recently been identified, and is now delineated in detail. A phenotypically homogeneous group of five families from Australia, Britain and Canada, containing 47 affected individuals, was studied. The largest family contained 25 affected individuals spanning six generations. This disorder is characterized by clusters of brief nocturnal motor seizures, with hyperkinetic or tonic manifestations. Subjects often experienced an aura, and remained aware throughout the attacks. Seizures occurred in clusters (mean eight attacks/night) typically as the individual dozed, or shortly before awakening. The epilepsy usually began in childhood, and persisted through adult life, with considerable intra-family variation in severity. Seizures were often misdiagnosed as benign nocturnal parasomnias, psychiatric and medical disorders. Interictal EEG studies were unhelpful. Ictal video-EEG studies showed that the attacks were partial seizures with frontal lobe seizure semiology. Neuro-imaging was normal. Carbamazepine monotherapy was frequently effective. This disorder showed autosomal dominant inheritance. Recognition of this entity is clinically important for diagnosis, appropriate therapy and genetic counselling. Moreover, this disorder now offers an opportunity to identify a gene for partial epilepsy.

A new mixed finite element method for computing viscoelastic flows

Abstract: A new mixed finite element method for computing viscoelastic flows is presented. The mixed formulation is based on the introduction of the rate of deformation tensor as an additional unknown. Contrary to the popular EVSS method [D. Rajagopalan, R.A. Brown and R.C. Armstrong, J. Non-Newtonian Fluid Mech., 36 (1990) 159], no change of variable is performed into the constitutive equation. Hence, the described method can be used to compute solutions of rheological models where the EVSS method does not apply. The numerical strategy uses a decoupled iterative scheme as a preconditioner for the GMRES algorithm. The stability and the robustness of the method are investigated on two benchmark problems: the 4:1 contraction flow problem and the stick-slip flow problem. Numerical results for the PTT [N. Phan-Thien and R.I. Tanner, J. Non-Newtonian Fluid Mech., 2 (1977) 353] and the Grmela [J. Grmela, J. Rheology, 33 (1989) 207] models show that our method is remarkably stable and cheap in computer time and memory.

Structural model for the β-amyloid fibril based on interstrand alignment of an antiparallel-sheet comprising a C-terminal peptide

Abstract: Amyloids are a class of noncrystalline, yet ordered, protein aggregates. A new approach was used to provide the initial structural data on an amyloid fibril—comprising a peptide (β34–42) from the C-terminus of the β-amyloid protein—based on measurement of intramolecular 13C–13C distances and 13C chemical shifts by solid-state 13C NMR and individual amide absorption frequencies by isotope-edited infrared spectroscopy. Intermolecular orientation and alignment within the amyloid sheet was determined by fitting models to observed intermolecular 13C–13C couplings. Although the structural model we present is defined to relatively low resolution, it nevertheless shows a pleated antiparallel β-sheet characterized by a specific intermolecular alignment.

Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity

Abstract: We investigated in anesthetized cats the progressive development from EEG-synchronized sleep patterns to low-frequency (

Corticothalamic projections from the cortical barrel field to the somatosensory thalamus in rats: a single-fibre study using biocytin as an anterograde tracer.

Abstract: This study investigated the pattern of axonal projections of single corticothalamic neurons from the cortical barrel field representing the vibrissae in the rat. Microiontophoretic injections of biocytin were performed in cortical layers V and VI to label small pools of corticothalamic cells and their intrathalamic axonal projections. After a survival period of 48 h, the animals were perfused and the tissue was processed for biocytin histochemistry. On the basis of the intrathalamic distribution of axonal fields and of the types of terminations found in the thalamus, four types of corticothalamic projections were identified. (i) Cells of the upper part of layer VI projected exclusively to the ventral posteromedial (VPm) nucleus, where they arborized in long rostrocaudally oriented bands or 'rods'. (ii) All cells of the lower part of layer VI projected to the medial part of the thalamic posterior group (Pom) but the vast majority of them also collateralized in VPm where they participated in the formation of rods. (iii) A minority of corticothalamic cells in the lower portion of layer VI, possibly located under the interbarrel spaces (septae), arborized exclusively in Pom. (iv) The corticothalamic projection of layer V cells originated from collaterals of corticofugal cells whose main axons ran caudally towards the brainstem. These collaterals arborized exclusively in Pom or in the central lateral nucleus. All corticothalamic cells from layer VI displayed the same type of axonal network, made of long branches decorated by terminal buttons emitted en passant at the tip of fine stalks. Corticothalamic fibres arising from layer V pyramids, however, remained smooth as they ran across the lateral thalamus and they generated in Pom one or two clusters of large boutons. All corticothalamic axons derived from layer VI cells, but not those derived from layer V cells, gave off collaterals as they traversed the thalamic reticular complex. These observations are discussed in the light of previous studies bearing on the topological organization and function of corticothalamic projections to VPm and Pom in rats. The possibility that a similar cellular specificity and a similar organizational plan may characterize corticothalamic relationships in other sensory systems is also considered.

The HERITAGE family study. Aims, design, and measurement protocol

Abstract: The HERITAGE family study (HEalth, RIsk factors, exercise Training And GEnetics) will document the role of the genotype in the cardiovascular, metabolic, and hormonal responses to aerobic exercise training. A consortium of five universities in the United States and Canada are involved in carrying out the study. A total of 90 Caucasian families and 40 African-American families with both parents and three or more biological adult offspring are being recruited, tested, exercise-trained in the laboratory with the same program for 20 wk, and re-tested. Oxygen uptake, respiratory exchange ratio, blood pressure, heart rate, cardiac output, blood lactate, glucose, and free-fatty acids are measured during exercise, and maximal oxygen uptake is determined before and after training. Plasma lipids, lipoproteins and apoproteins, glucose and insulin response to an intravenous glucose load, plasma sex steroids and glucocorticoids, and body fat and fat distribution are assessed. Dietary and activity habits and other life style components are assessed by questionnaires, prior to, during, and after training. A variety of genetic analyses will be undertaken, including heritability studies and major gene effects, for each phenotype and its response to regular exercise. Cell lines are established, and DNA sequence variation at a variety of molecular markers will be determined for association and linkage studies.

Synchronization of ovarian follicular waves with a gonadotropin-releasing hormone agonist to increase the precision of estrus in cattle: a review.

Abstract: Treatment with GnRH and PGF2 alpha is a practical method for controlling ovarian follicular and luteal functions and increasing the precision of estrus synchronization in cyclic and acyclic postpartum cows and heifers. This method reduces considerably the period of time needed for estrus detection; it synchronizes the estrous cycle of 70 to 80% of the cyclic cows to within a 4-d interval without any detrimental effect on the fertility rate (65 to 85%). Moreover, resumption of ovarian activity and normal fertility in acyclic cows in favored. Administration of GnRH eliminates the large follicles by ovulation or atresia and induces emergence of a new follicular wave within 3 to 4 d after treatment at any stage of the estrous cycle, but it limits further growth of these emerging follicles by increasing atresia. The precision of estrus and the unaltered fertility rate is due to the synchronized selection of a new larger growing follicle, which becomes the ovulatory follicle after PGF(2 alpha)-induced luteolysis 6 d after GnRH treatment. Also, fixed-time AI programs without the need for estrus detection may be possible using a second injection of GnRH in a GnRH-PGF(2 alpha)-GnRH protocol to ovulate the selected follicle at a precise time. We describe a physiological model to explain how the precision of estrus is improved following PGF(2 alpha)-induced luteolysis, via the effect of pretreatment with GnRH on follicular development and luteal functions in cattle. Application of this model to the development of reliable methods of fixed-time insemination is also explored.

Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer

Abstract: Purpose: The aim of the present study isto investigate whether combined androgen blockade associated with radiation therapy for localized prostate cancer decreases at 12 and 24 months the rate of ppsitive follow-up biopsies and serum PSA compared to radiation therapy alone. This is the report of an interim analysis. Methods and Materials: One hundred and twenty patients with clinical Stage B1-T2a, B2-T2b/T2c, and C-T3/ T4, adenocarcinoma of the prostate were entered in a prospective randomized study. After written informed consent, the subjects were randomly allocated between external beam radiation therapy (EBRT) alone (group 1), 3 months of neoadjuvant combination therapy (LHRH-agnist + Flutamide) prior to EBRT (group 2), and a third group receiving combination therapy 3 months before, during, and 6 months after EBRT. There is no significant difference between the three groups concerning age, stage of disease, grade of tumor, and pretreatment PSA levels. Control transrectal ultrasound (TRUS)-guided needle biopsies (one core was taken from the initial cancer site regardlss of the presence or absence of TRUS abnormalities) were done 12 and 24 months after the end of EBRT. Serum PSA measurements were done on schedule visits. Results: Ninety-two and 68 patients underwent biopsies at 12 and 2 months, respectively, after the end of radiation therapy. While 62% of control patients at 12 months in Group 1 discloed residual neoplasm, only 30 and 4% showed residual disease in groups 2 and 3, respectively ( p = 0.0005). When looking at 24 months, 65, 28, and 5% showed residual cancer for groups 1, 2, and 3, respectively ( p = 0.00001). The PSA measurements indicate also at 12 months a difference between the three groups ( p Conclusion: The preliminary analysis of this clinical trial indicates that patients treated with radiation therapy alone show a significantly higher rate of positive biopsies at 12 and 24 months after the end of radiation therapy as compared with those treated with total antiandrogen blockade (TAB) and radiation therapy. When analyzing the median PSA serum levels, we found the same advantage at 12 mnths, but, at the time of the analysis at 24 months, the PSA levels are not different between groups 2 and 3.

Crystal Structure of the Biphenyl-Cleaving Extradiol Dioxygenase from a PCB-Degrading Pseudomonad

Abstract: Polychlorinated biphenyls (PCBs) typify a class of stable aromatic pollutants that are targeted by bioremediation strategies. In the aerobic degradation of biphenyl by bacteria, the key step of ring cleavage is catalyzed by an Fe(II)-dependent extradiol dioxygenase. The crystal structure of 2,3-dihydroxybiphenyl 1,2-dioxygenase from a PCB-degrading strain of Pseudomonas cepacia has been determined at 1.9 angstrom resolution. The monomer comprises amino- and carboxyl-terminal domains. Structural homology between and within the domains reveals evolutionary relationships within the extradiol dioxygenase family. The iron atom has five ligands in square pyramidal geometry: one glutamate and two histidine side chains, and two water molecules.

DHEA and Peripheral Androgen and Estrogen Formation: Intracrinology

Abstract: Despite the fact that the concentration of dehydroepiandrosterone sulfate (DHEAS) in the circulation of adult men and women is higher than that of any other steroid, except cholesterol, the biologic function of this steroid as well as that of DHEA has received little attention. It is remarkable that man, in addition to possessing very sophisticated endocrine and paracrine systems, has largely vested sex steroid formation in peripheral tissues.IJ In fact, although the ovaries and testes are the exclusive sources of androgens and estrogens in lower mammals, the situation is very different in higher primates, where active sex steroids are in large part or entirely synthesized locally in peripheral tissues, thus providing control to target tissues which adjust the formation and metabolism of sex steroids to local requirements. Man, with some other primates, is thus unique in having adrenals that secrete large amounts of the precursor steroids DHEAS and DHEA which are converted into androstenedione (Cdione) and then into potent androgens and/or estrogens in peripheral t iss~es.l-~ Adrenal secretion of DHEA and DHEAS increases during adrenarche in children at the age of 6-8 years, and maximal values of circulating DHEAS are reached between the ages of 20 and 30 years. Thereafter, serum DHEA and DHEAS levels decrease markedly.\"' In fact, at 70 years of age, serum DHEAS levels are at approximately 20% of their peak values, whereas they decrease by up to 95% by the age of 85-90 years.\" The 70-95% reduction in the formation of DHEAS by the adrenals during aging results in a dramatic reduction in the formation of androgens and estrogens in peripheral target tissues, which could well be involved in the pathogenesis of age-related diseases such as insulin re~istance?.~ cardiovascular disease,I0 and obesity.I1J2 Low circulating levels of DHEAS and DHEA have been found in patients with breastI3 and prostateI4 cancer, and DHEA has been found to exert antioncogenic activity in a series of animal model^.'^-'^ DHEA has also been shown to have immunomodulatory effects in vitroI8 and in vivo in fungal and viral diseasesL9 including HIV.20 On the other hand, a stimulatory effect of DHEA on the immune system has been described in postmenopausal Transformation of the adrenal precursor steroids DHEAS and DHEA into androgens and/or estrogens in peripheral target tissues depends on the level of expression of the various steroidogenic and metabolizing enzymes in each of these tissues. This sector of endocrinology that focuses on intracellular hormone formation and action has been called intracrin~logy.~.~ Knowledge in this area has recently made rapid progress with the elucidation of the structure of most of the tissuespecific genes that encode the steroidogenic enzymes responsible for the transforma-

A general surface approach to the integration of a set of range views

Abstract: This paper presents a new and general solution to the problem of range view integration. The integration problem consists in computing a connected surface model from a set of registered range images acquired from different viewpoints. The proposed method does not impose constraints on the topology of the observed surfaces, the position of the viewpoints, or the number of views that can be merged. The integrated surface model is piecewise estimated by a set of triangulations modeling each canonical subset of the Venn diagram of the set of range views. The connection of these local models by constrained Delaunay triangulations yields g non-redundant surface triangulation describing all surface elements sampled by the set of range views. Experimental results show that the integration technique can be used to build connected surface models of free-form objects. No integrated models built from objects of such complexity have yet been reported in the literature, It is assumed that accurate range views are available and that frame transformations between all pairs of views can be reliably computed. >