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Showing papers by "Université de Sherbrooke published in 1996"


Journal ArticleDOI
TL;DR: It is demonstrated that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels and was also greater in patients with higher pretreatment levels of LDL cholesterol.
Abstract: Background In patients with high cholesterol levels, lowering the cholesterol level reduces the risk of coronary events, but the effect of lowering cholesterol levels in the majority of patients with coronary disease, who have average levels, is less clear. Methods In a double-blind trial lasting five years, we administered either 40 mg of pravastatin per day or placebo to 4159 patients (3583 men and 576 women) with myocardial infarction who had plasma total cholesterol levels below 240 mg per deciliter (mean, 209) and low-density lipoprotein (LDL) cholesterol levels of 115 to 174 mg per deciliter (mean, 139). The primary end point was a fatal coronary event or a nonfatal myocardial infarction. Results The frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group, an absolute difference of 3 percentage points and a 24 percent reduction in risk (95 percent confidence interval, 9 to 36 percent; P = 0.003). Coronary bypass surgery was needed in 7.5 per...

7,272 citations


Journal ArticleDOI
TL;DR: Because ATPDase activity is lost with endothelial cell activation, overexpression of the functional enzyme, or a truncated mutant thereof, may prevent platelet activation associated with vascular inflammation.

559 citations


Journal ArticleDOI
03 May 1996-Cell
TL;DR: A new step in telomere maintenance, cell cycle-regulated degradation of the C1-3A strand, which can generate a potential substrate for telomerase andTelomere-binding proteins at every telomeres is suggested.

319 citations


Journal Article
TL;DR: Hylan G-F 20 provided good clinical benefits and an acceptable safety profile in current clinical practice and the occurrence of adverse events after an intraarticular hylan injection is infrequent and unpredictable and is not necessarily hylan related, although injection related.
Abstract: Objective. To evaluate viscosupplementation with intraarticular hylan G-F 20 in current clinical practice. Methods. A retrospective study of all patients with osteoarthritis of the knee treated with hylan by 5 Canadian clinicians over a period of 2.5 years. Results. A total of 1537 injections were performed in 336 patients involving 458 knees. The overall response and the change of activity level were judged better or much better for 77 and 76% of the treated knees after the first course of treatment (3 weekly injections), and 87 and 84% after a 2nd course. The mean time elapsing between the first and 2nd course, 8.2 ± 0.5 months, is an evaluation of the duration of benefits. Local adverse events were observed in 28 patients (32 knees), with an overall rate of 2.7% adverse events per injection, 7.0% per joint, and 8.3% per patient. No systemic adverse events were noted in any patient. The adverse events were characterized by pain and/or transient swelling of the injected joint, mostly mild or moderate in intensity, and 72% of the adverse events were considered to be possibly or probably related to the injection. The incidence of adverse events is significantly influenced by the injection technique : 5.2% adverse events per injection with a medial approach to a partially bent knee, and 2.4% (straight medial) and 1.5% (straight lateral). After an adverse event, clinical improvement still occurred in 69% of the affected knees. Conclusion. Hylan G-F 20 provided good clinical benefits and an acceptable safety profile in current clinical practice. The occurrence of adverse events after an intraarticular hylan injection is infrequent and unpredictable and is not necessarily hylan related, although injection related.

316 citations


Journal ArticleDOI
TL;DR: In this article, momentum angular distributions of the nonlinear multiphoton photoelectron spectra from intense ultrashort pulse ionization of H2+ molecular ions show signatures of electron diffraction from two nuclei.

301 citations


Journal ArticleDOI
TL;DR: In this paper, the Sherbrooke APD-PET scanner has been evaluated in terms of resolution, sensitivity, count rate, random and scatter fractions, contrast and relative activity recovery as a function of object size.
Abstract: The design features and engineering constraints of a PET system based on avalanche photodiode (APD) detectors have been described in a previous report. Here, the authors present the initial results obtained with the Sherbrooke APD-PET scanner, a very high spatial resolution device designed for dynamic imaging of small and medium-sized laboratory animals such as rats, cats, rabbits and small monkeys. Its physical performance has been evaluated in terms of resolution, sensitivity, count rate, random and scatter fractions, contrast and relative activity recovery as a function of object size. The capabilities of the scanner for biomedical research applications have been demonstrated using phantom and animal studies.

251 citations


Journal ArticleDOI
TL;DR: The influence of the Coulomb focusing, in combination with multiple returns, focuses parts of the electron wave function, increasing the efficiency of such intense field processes as multiphoton double ionization.
Abstract: In the intense field (long-wavelength) limit, the oscillating motion of an electron wave packet leads to multiple passes by the scattering Coulomb center. The influence of the Coulomb focusing, in combination with multiple returns, focuses parts of the electron wave function, increasing the efficiency of such intense field processes as multiphoton double ionization. Our calculations show enhancement by more than an order of magnitude for multiphoton double ionization of He at 0.8 \ensuremath{\mu}m.

249 citations


Journal ArticleDOI
TL;DR: The effect of a supervised physical activity program on the physical and psychological health of osteopenic women is described.
Abstract: OBJECTIVE: To describe the effect of a supervised physical activity program on the physical and psychological health of osteopenic women DESIGN: A randomized controlled trial SETTING: Sherbrooke, Quebec, Canada PARTICIPANTS: A total of 124 community-living postmenopausal women, between 50 and 70 years of age, with low bone mass took part in the study INTERVENTION: Subjects allocated to the experimental group performed weight-bearing exercises (walking, stepping up and down from benches), aerobic dancing, and flexibility exercises for 60 minutes, three times a week, over a period of 12 months All subjects were invited to attend bi-monthly educational seminars covering topics related to osteoporosis OUTCOME MEASURES: Spinal and femoral bone mineral density (BMD), functional fitness (flexibility, coordination, agility, strength/endurance, cardiorespiratory endurance), psychological well-being, back pain intensity, and self-perceived health RESULTS: Spinal BMD stabilized in the exercisers while decreasing significantly in the controls (P = 031) No change in femoral BMD was observed in either group (P = 597) Four of the five parameters chosen to evaluate functional fitness, namely flexibility, agility, strength, and endurance, were affected positively by the exercise program (all P < 01) Adjusting for prescores by means of an analysis of covariance revealed a significant difference between the groups in psychological well-being, which favored the exercisers (P = 012) After 12 months, back pain reported by exercisers was lower than that reported by controls (P = 008) Finally, self-perceived health increased in the exercise group, whereas no difference was observed in the control group (P = 790) CONCLUSION: These results suggest that after 12 months, exercising can produce a significant increase above initial levels in the functional fitness, well-being, and self-perceived health of osteopenic women Intensity of back pain can also be lowered by exercise The exercise program succeeded in stabilizing spinal BMD but had no effect on femoral BMD

214 citations


Journal ArticleDOI
TL;DR: Using a novel in-gel hybridization technique, it is shown directly that in yeast strains lacking the TLC1 gene encoding the yeast telomerase RNA, TG1-3 single-stranded DNA was generated on chromosomal and plasmid telomeres.
Abstract: Current models of telomere replication predict that due to the properties of the polymerases implicated in semiconservative replication of linear DNA, the two daughter molecules have one end that is blunt and one end with a short 3′ overhang. Telomerase is thought to extend the short 3′ overhang to produce long single-stranded overhangs. Recently, such overhangs, or TG 1–3 tails, were shown to occur on both telomeres of replicated linear plasmids in yeast. Moreover, indirect evidence suggested that the TG 1–3 tails also occurred in a yeast strain lacking telomerase. We report herein a novel in-gel hybridization technique to probe telomeres for single-stranded DNA. Using this method, it is shown directly that in yeast strains lacking the TLC1 gene encoding the yeast telomerase RNA, TG 1–3 single-stranded DNA was generated on chromosomal and plasmid telomeres. The single-stranded DNA only appeared in S phase and was sensitive to digestion with a single-strand-specific exonuclease. These data demonstrate that during replication of telomeres, TG 1–3 tails can be generated in a way that is independent of telomerase-mediated strand elongation. In wild-type strains, these TG 1–3 tails could subsequently serve as substrates for telomerase and telomere binding proteins on all telomeres.

210 citations


Journal ArticleDOI
TL;DR: The results demonstrate that the AT1 receptor inhibit the process of differentiation induced by dibutyryl cAMP, whereas the AT2 receptors potentiate this effect, illustrating negative cross-talk interaction between the two types of Ang II receptors.

195 citations


Journal ArticleDOI
TL;DR: This article found that the combined effects of country of design and country of assembly cues has a stronger impact than brand name on consumer evaluation of quality and purchase value of automobiles, VCRs and shoes.
Abstract: The data for this research were collected from 365 male respondents through two separate studies at two different time periods using two different formats. Results indicated that the combined effects of country of design and country of assembly cues has a stronger impact than brand name on consumer evaluation of quality and purchase value of automobiles, VCRs and shoes. Magnitude of a priori cue differentiation played a strong role in product evaluation. Favorableness of a brand or country-of-origin cues is considerably modified when a consumer is provided with additional product-related information.

Journal ArticleDOI
TL;DR: Using ultrashort pulse multiphoton ionization, a wave packet in the I.2 state is launched that dissociates into the fragments and no enhancement is seen with perpendicular polarization in agreement with the model of enhanced ionization by electron localization.
Abstract: Using ultrashort pulse multiphoton ionization, we launch a wave packet in the ${\mathrm{I}}_{2}^{\phantom{\rule{0ex}{0ex}}2+}$ state that dissociates into the fragments ${\mathrm{I}}^{2+}$ and I. We measure its multiphoton ionization probability as a function of its internuclear distance with an intense delayed probe pulse. If the probe pulse is polarized parallel to the internuclear axis, we observe a peak in the ionization yield at a critical distance of 5--6 \AA{}. No such enhancement is seen with perpendicular polarization in agreement with the model of enhanced ionization by electron localization.

Journal ArticleDOI
TL;DR: Results show that for bighorn sheep ewes, sons have a greater life-history cost than daughters, suggesting a differential maternal investment in the sexes.
Abstract: bAlberta Fish and Wildlife, Box 1059, Canmore, Alberta TOL 0M0, Canada Differential maternal investment theory predicts that in sexually dimorphic and polygynous species mothers should invest more in sons than in daughters. We tested the hypothesis that bighorn ewes that raise sons incur greater reproductive costs than ewes that raise daughters. Although ewe mass gain during lactation and subsequent winter body mass loss were independent of lamb sex, lambs born the year following the weaning of a son had lower survival than lambs born after a daughter. The effects of lamb sex on subsequent reproductive success of ewes became more evident at high population density. Lamb sex did not affect maternal survival. Population density, weather, and ewe age did not alter the relationship between lamb sex and subsequent reproductive success of the ewe. The year after weaning a son, ewes were more likely to have a daughter than a son, while ewes that had previously weaned a daughter had similar numbers of sons and daughters. Our results show that for bighorn sheep ewes, sons have a greater life-history cost than daughters, suggesting a differential maternal investment in the sexes. Key words. costs of reproduction, differential maternal investment, OxAs canadensis, reproductive success, sex ratio. [Behav Ecol 7:60-68 (1996)]

Journal ArticleDOI
TL;DR: The newly discovered neuropeptide, nociceptin (alias orphanin FQ), was tested for its potential direct effects, as well as for its ability to modify the electrically evoked contractions in several isolated organs suspended in vitro.

Journal ArticleDOI
TL;DR: In this paper, a quasiclassical approach to correct electron motion following tunneling ionization in intense laser fields, for the presence of the Coulomb potential, is described.
Abstract: We describe a quasiclassical approach to correct electron motion following tunneling ionization in intense laser fields, for the presence of the Coulomb potential. The technique is applied to model the dependence of high-harmonic generation on the ellipticity of the incident laser field. We present experimental data on the harmonics with photon energies close to the ionization potential of an atom, identify their source, and explain their unusual dependence on the ellipticity of the incident laser field. Our calculations are in good agreement with experimental data. \textcopyright{} 1996 The American Physical Society.

Journal ArticleDOI
TL;DR: The 2.4 Å X-ray crystal structure of a protein with chitosan endo-hydrolase activity isolated from Streptomyces N174 reveals a structural core shared with several classes of lysozyme and barley endochitinase, in spite of a lack of shared sequence.
Abstract: We report the 2.4 A X-ray crystal structure of a protein with chitosan endo-hydrolase activity isolated from Streptomyces N174. The structure was solved using phases acquired by SIRAS from a two-site methyl mercury derivative combined with solvent flattening and non-crystallographic two-fold symmetry averaging, and refined to an R-factor of 18.5%. The mostly α-helical fold reveals a structural core shared with several classes of lysozyme and barley endochitinase, in spite of a lack of shared sequence. Based on this structural similarity we postulate a putative active site, mechanism of action and mode of substrate recognition. It appears that Glu 22 acts as an acid and Asp 40 serves as a general base to activate a water molecule for an SN2 attack on the glycosidic bond. A series of amino-acid side chains and backbone carbonyl groups may bind the polycationic chitosan substrate in a deep electronegative binding cleft.

Book
01 Jan 1996
TL;DR: This work describes how natural domain information, of a “strategic” nature, can be expressed in a temporal logic, and then utilized to effectively control a forward-chaining planner.
Abstract: Over the years increasingly sophisticated planning algorithms have been developed. These have made for more efficient planners, but unfortunately these planners still suffer from combinatorial explosion. Indeed, recent theoretical results demonstrate that such an explosion is inevitable. It has long been acknowledged that domain independent planners need domain dependent information to help them plan effectively. In this work we describe how natural domain information, of a “strategic” nature, can be expressed in a temporal logic, and then utilized to effectively control a forward-chaining planner. There are numerous advantages to our approach, including a declarative semantics for the search control knowledge; a high degree of modularity (the more search control knowledge utilized the more efficient search becomes); and an independence of this knowledge from the details of the planning algorithm. We have implemented our ideas in the TLPLAN system, and have been able to demonstrate its remarkable effectiveness in a wide range of planning domains.

Journal ArticleDOI
TL;DR: In this article, the effect of limestone microfilier replacement of cement on the mechanical performance and cost effectiveness of low w c ratio superplasticized portland cement mortars was investigated.

Journal ArticleDOI
TL;DR: This work suggests that researchers are more likely to attempt to publish sex ratio data when alternative evolutionary hypotheses concerning a female’s offspring sex ratio predict opposing deviations from unity.
Abstract: Alternative evolutionary hypotheses concerning a female’s offspring sex ratio predict opposing deviations from unity I suggest that researchers are more likely to attempt to publish sex ratio data

Journal ArticleDOI
TL;DR: Increased dye uptake by the cells also correlated with their activities, except for the lipophilic ZnPcI4, which showed the highest cell uptake but little phototoxicity, suggesting that care should be taken in interpreting dye toxicity data, which involve in vitro cell manipulations in dye‐free medium, particularly during in vitro/in vivo protocols.
Abstract: Radioiodinated zinc phthalocyanine including [125I]ZnPcI4 and differently sulfonated [65Zn]ZnPcS (ZnPcS4, ZnPcS3, ZnPcS2 and ZnPcS1.75, a mixture of adjacent di and 25% mono) were prepared in order to study cell uptake and release kinetics in EMT-6 cells. The same compounds were evaluated for their in vitro phototoxicity and the biological parameters were compared to partition coefficients to arrive at quantitative structure-activity relationships (QSAR). At 1 microM in 1% serum, at 37 degrees C, all dyes showed rapid cell uptake during the first hour followed by a slow accumulation phase. After 24 h, the highest cellular concentration was observed with the lipophilic ZnPcI4, followed by the amphiphilic ZnPcS2 and ZnPcS1.75. The hydrophilic ZnPcS4 and ZnPcS3 showed lower uptake. Dye release from dye-loaded cells during incubation in dye-free medium could reach up to 60% and was shown to depend mainly on the amount of drug incorporated rather than the type of compound. These results suggest that care should be taken in interpreting dye toxicity data, which involve in vitro cell manipulations in dye-free medium, particularly during in vitro-in vivo protocols. The EMT-6 cell survival after 1 h or 24 h incubation with 1 microM dye in 1% serum followed by exposure to red light was assessed by means of the colorimetric 3-(4,5-dimethylthiazol-2-yl)-diphenyl-tetrazolium bromide (MTT) assay. Photocytotoxicities correlated inversely with the tendencies of the dyes to aggregate. Increased dye uptake by the cells also correlated with their activities, except for the lipophilic ZnPcI4, which showed the highest cell uptake but little phototoxicity. The QSAR between phototoxicity and the log of the partition coefficients (phosphate-buffered saline and n-octanol) gave a parabola with optimal partition values corresponding to the adjacent sulfonated ZnPcS2.

Journal ArticleDOI
TL;DR: The time-dependent Schrodinger equation for H2 in a 600-nm, intense laser field is solved numerically for a model which uses the exact three-body Hamiltonian with one-dimensional nuclear motion restricted to the direction of the laser electric field and three-dimensional electronic motion.
Abstract: The time-dependent Schr\"odinger equation for ${\mathrm{H}}_{2}$${\mathrm{}}^{+}$ in a 600-nm, intense (I\ensuremath{\geqslant}${10}^{14}$ W/${\mathrm{cm}}^{2}$) laser field is solved numerically for a model which uses the exact three-body Hamiltonian with one-dimensional nuclear motion restricted to the direction of the laser electric field and three-dimensional electronic motion. High ionization rates of ${\mathrm{H}}_{2}$${\mathrm{}}^{+}$ are found, exceeding those of neutral atomic hydrogen. This confirms, by the rigorous, full dynamical calculation, the recently discovered charge-resonance-enhanced ionization (CREI)---all previous demonstrations of CREI were based on the ``frozen nuclei'' model. The numerical kinetic-energy spectra of dissociating fragments are compared with recent experimental results. They can be interpreted by a simple bond softening mechanism (or laser-induced avoided crossing in a dressed-state representation), in which the binding forces are completely suppressed by the strong electric field and thus the dissociating fragments move as free particles with a kinetic energy close to their initial vibrational energy until they reach a critical distance R=${\mathit{R}}_{\mathit{c}}$\ensuremath{\cong}8 bohr, where they are rapidly ionized, due to CREI. The harmonic generation spectra calculated from our non-Born-Oppenheimer simulations show that the high harmonics are also generated when the nuclei cross this critical distance R=${\mathit{R}}_{\mathit{c}}$. \textcopyright{} 1996 The American Physical Society.

Journal ArticleDOI
TL;DR: In this article, the authors attempted to derive a definition of sportsmanship by applying premises from social psychological theories and research, and found that sportsmanship meanings and labels attached to given behaviors are learned through interpersonal interactions with various sport participants and that eventually a consensual agreement develops regarding the nature of sportmanship.
Abstract: One major problem with research conducted on sportsmanship is the absence of an accepted definition. The purpose of this study was to attempt to derive a definition of sportsmanship by applying premises from social psychological theories and research. A major assumption of this perspective is that sportsmanship meanings and labels attached to given behaviors are learned through interpersonal interactions with various sport participants and that eventually a consensual agreement develops regarding the nature of sportsmanship. It thus follows that a meaningful definition of sportsmanship should be obtained through the athletes themselves. In this study, 1056 male and female athletes completed a questionnaire which contained various items pertaining to sportsmanship. Results from a factor analysis revealed the presence of 5 factors corresponding to the respect and concern for: a) one's full commitment toward sport participation, b) the rules and officials. c) social conventions, d) the opponent, as ...

Journal ArticleDOI
TL;DR: In this paper, structural data, nomenclature, synthetic routes and spectral properties of the majority of known azaanalogs of phthalocyanines are presented, which explain their tendency to form stable hydrates and their specific affinity for protons in acidic media.

Journal ArticleDOI
TL;DR: In this article, Taylor-type polycrystal plasticity models with various single slip hardening laws are evaluated by studying the large strain behaviour of FCC polycrystals during reversed torsion.

Journal ArticleDOI
TL;DR: In this paper, an end-loaded split (ELS) test for measuring the stable crack growth resistance of composites under mode II loading was used to determine the effective crack length in the range of large deflection.

Journal ArticleDOI
TL;DR: Formulation in the biodegradable NP improved PDT response of the tumour while providing prolonged tumour sensitivity towards PDT.
Abstract: Hexadecafluoro zinc phthalocyanine (ZnPcF16), a second-generation sensitizer for the photodynamic therapy (PDT) of cancer, was formulated in polyethylene-glycol-coated poly(lactic acid) nanoparticles (PEG-coated PLA-NP) and tested in EMT-6 tumour-bearing mice for its photodynamic activity. The tumour response was compared to that induced by the same dye formulated as a Cremophor EL (CRM) emulsion. Formulation in the biodegradable NP improved PDT response of the tumour while providing prolonged tumour sensitivity towards PDT.

Journal ArticleDOI
TL;DR: Human African trypanosomiasis (HAT) control programs existed during the colonial era in the Belgian Congo until the end of the 1980s, when the number of new HAT cases began to increase from the relatively stable numbers of 4000-6000 during 1969-1981 to almost 10,000 during 1993-1994, when some foreign aid was again available.

Journal ArticleDOI
TL;DR: In this paper, the search for a volunteer is modelled as a war of attrition in which everyone is tempted to just wait for someone else to do it, and the volunteer will be, ceteris paribus, the individual for whom the benefit/cost ratio of performing the public service is largest, the one most impatient to consume it, or the one who stands to benefit from it the longest.

Journal ArticleDOI
TL;DR: The results summarized in this paper indicate that the human isolated umbilical vein is a sensitive preparation containing both B1 and B2 receptors.
Abstract: 1. The human umbilical vein has been found to contract in response to bradykinin (BK) and desArg9BK. 2. The rank order of potency of agonists, in the presence of the B1 receptor antagonist Lys[Leu8]desArg9BK, is as follows: [Hyp3, Tyr(Me)8]BK (pD2 8.88) = [Hyp3]BK (pD2 8.86) = LysBK (pD2 8.81) > or = BK (pD2 8.60) >> [Aib7]BK (pD2 6.38) >> desArg9BK and LysdesArg9BK (inactive). 3. Hoe 140 (pA2 8.42) inhibits the effects of BK while other B2 receptor peptide antagonists are very weak and WIN 64338 is practically inactive. 4. Venoconstrictor responses to desArg9BK of fresh tissues increase with time during the in vitro incubation and reach a maximum after 4-6 h. The activity of Hoe 140 (pA2 5.48) is negligible against B1 receptor agonists. 5. When measured in the presence of the selective B2 receptor antagonist Hoe 140 (400 nM), the order of potency of kinin related peptides on the B1 receptor is Lys[desArg9]BK (pD2 8.60) > desArg9BK (pD2 6.69). BK, LysBK, [Hyp3]BK and other B2 receptor agonists are inactive. 6. The B1 receptor antagonist, Lys[Leu8]desArg9BK (pA2 7.99), inhibits the response of the human vein to B1 receptor agonists (LysdesArg9BK or desArg9BK), but do not alter the effect of BK. 7. The results summarized in this paper indicate that the human isolated umbilical vein is a sensitive preparation containing both B1 and B2 receptors. The human B2 receptor shows some similarity with that of the rabbit (at least for agonist potencies) and differs from the B2 receptor of the guinea-pig. Compared to the rabbit B1 receptor, the human B1 receptor shows low sensitivity to peptides that lack the N-terminal Lys.

Journal Article
TL;DR: The results show that the Tyr302 in the NPXnY motif of the human angiotensin II receptor type 1 is not essential for agonist binding properties or for internalization of the receptor but plays an important role in transmembrane signaling.
Abstract: The NPXnY motif is involved in the internalization process of several types of receptors, including lipoprotein receptors and G protein-coupled receptors. We replaced Tyr302 with either phenylalanine or alanine in the NPLFY site of the human angiotensin II receptor type 1 and determined the pharmacological properties of the resulting mutant receptors. Competitive binding experiments revealed that COS-7 cells transfected with either the wild-type or mutant receptors expressed approximately the same amount of high affinity binding sites (Bmax 70,000 sites/cell and Kd approximately 2 nM). Photoaffinity labeling of both native and mutant receptors revealed apparent molecular masses of 110 kDa. Incubation of transfected cells with 0.2 nM [125I]Ang II at 37 degrees revealed an efficient internalization of the wild-type receptor and the mutant receptors, although the mutant receptors were internalized at a slower rate. Interestingly, however, the transmembrane signaling was severely impaired in transfected cells expressing mutant receptors. No significant production of inositol-1,4,5-trisphosphate was observed when these cells were challenged for 3 min with a concentration of angiotensin II as high as 1 microM. This is in contrast to the dose-dependent stimulation of inositol-1,4,5-trisphosphate production in cells expressing the wild-type receptor. Thus, our results show that the Tyr302 in the NPXnY motif of the human angiotensin II receptor type 1 is not essential for agonist binding properties or for internalization of the receptor but plays an important role in transmembrane signaling.