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See detailPreclinical and clinical pharmacology of alcohol dependence
Tambour, Sophie ULg; Quertemont, Etienne ULg

in Fundamental & Clinical Pharmacology (2007), 21(1), 9-28

In recent years, advances in neuroscience led to the development of new medications to treat alcohol dependence and especially to prevent alcohol relapse after detoxification. Whereas the earliest ... [more ▼]

In recent years, advances in neuroscience led to the development of new medications to treat alcohol dependence and especially to prevent alcohol relapse after detoxification. Whereas the earliest medications against alcohol dependence were fortuitously discovered, recently developed drugs are increasingly based on alcohol's neurobiological mechanisms of action. This review discusses the most recent developments in alcohol pharmacotherapy and emphasizes the neurobiological basis of anti-alcohol medications. There are currently three approved drugs for the treatment of alcohol dependence with quite different mechanisms of action. Disulfiram is an inhibitor of the enzyme aldehyde dehydrogenase and acts as an alcohol-deterrent drug. Naltrexone, an opiate antagonist, reduces alcohol craving and relapse in heavy drinking, probably via a modulation of the mesolimbic dopamine activity. Finally, acamprosate helps maintaining alcohol abstinence, probably through a normalization of the chronic alcohol-induced hyperglutamatergic state. In addition to these approved medications, many other drugs have been suggested for preventing alcohol consumption on the basis of preclinical studies. Some of these drugs remain promising, whereas others have produced disappointing results in preliminary clinical studies. These new drugs in the field of alcohol pharmacotherapy are also discussed, together with their mechanisms of action. [less ▲]

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See detailPreclinical evidence for a beneficial impact of valproate on the response of small cell lung cancer to first-line chemotherapy
Hubaux, Roland; Vandermeers, Fabian ULg; Crisanti, Cecilia et al

in European Journal of Cancer (2010), 46

Prognosis of small cell lung carcinoma (SCLC) is particularly poor, less than 5% of patients with extensive stage being alive after two years.We hypothesized that SCLC chemotherapy could be improved by ... [more ▼]

Prognosis of small cell lung carcinoma (SCLC) is particularly poor, less than 5% of patients with extensive stage being alive after two years.We hypothesized that SCLC chemotherapy could be improved by using histone deacetylase (HDAC) inhibitors based on their ability to interfere with lysine acetylation and to alter gene expression. The goal of this study was to evaluate the anticancer efficacy of a HDAC inhibitor (valproate: VPA) on SCLC cells in combination with the standard chemotherapeutic first-line regimen (cisplatin + etoposide). We show that VPA induces apoptosis of small cell lung cancer cell lines and improves efficacy of cisplatin combined with etoposide. Both mitochondrial and death receptor pathways are involved in VPA-induced apoptosis. As expected for an HDAC inhibitor, VPA hyperacetylates histone H3. The mechanism of VPA pro-apoptotic activity involves induction of p21, inhibition of Bcl-xL, cleavage of Bid and phosphorylation of Erk and H2AX. In the presence of VPA, Bax is translocated from the cytoplasm to the mitochondria and cleaved in an 18 kDa isoform. Cytochrome c is released from the mitochondria into the cytosol. Transcriptomic analyses by microarray show that VPA modulates transcription of genes (Na+/ K+ ATPase, Bcl-xL) involved in chemoresistance to cisplatin and etoposide. Finally, the efficacy of VPA combined with cisplatin and etoposide is supported by preclinical models of SCLC cells engrafted into SCID mice. Together, these data demonstrate that VPA augments anticancer activity of cisplatin and etoposide, two components of the standard first-line chemotherapy of small cell lung cancer. [less ▲]

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See detailPreclinical radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H
Bretin, Florian ULg; Warnock, Geoffrey; Bahri, Mohamed Ali ULg et al

in European Journal of Nuclear Medicine and Molecular Imaging Research (2013), 3(1), 35

Background: [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to ... [more ▼]

Background: [18F]UCB-H was developed as a novel radiotracer with a high affinity for synaptic vesicle protein 2A, the binding site for the antiepileptic levetiracetam. The objectives of this study were to evaluate the radiation dosimetry of [18F]UCB-H in a preclinical trial and to determine the maximum injectable dose according to guidelines for human biomedical research. The radiation dosimetry was derived by organ harvesting and dynamic micro positron emission tomography (PET) imaging in mice, and the results of both methods were compared. Methods: Twenty-four male C57BL-6 mice were injected with 6.96 ± 0.81 MBq of [18F]UCB-H, and the biodistribution was determined by organ harvesting at 2, 5, 10, 30, 60, and 120 min (n = 4 for each time point). Dynamic microPET imaging was performed on five male C57BL-6 mice after the injection of 9.19 ± 3.40 MBq of [18F]UCB-H. A theoretical dynamic bladder model was applied to simulate urinary excretion. Human radiation dose estimates were derived from animal data using the International Commission on Radiological Protection 103 tissue weighting factors. Results: Based on organ harvesting, the urinary bladder wall, liver and brain received the highest radiation dose with a resulting effective dose of 1.88E-02 mSv/MBq. Based on dynamic imaging an effective dose of 1.86E-02 mSv/MBq was calculated, with the urinary bladder wall and liver (brain was not in the imaging field of view) receiving the highest radiation. Conclusions: This first preclinical dosimetry study of [18F]UCB-H showed that the tracer meets the standard criteria for radiation exposure in clinical studies. The dose-limiting organ based on US Food and Drug Administration (FDA) and European guidelines was the urinary bladder wall for FDA and the effective dose for Europe with a maximum injectable single dose of approximately 325 MBq was calculated. Although microPET imaging showed significant deviations from organ harvesting, the Pearson’s correlation coefficient between radiation dosimetry derived by either method was 0.9666. [less ▲]

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See detailPrecocious puberty associated with partial trisomy 18q and monosomy 11q
Mutesa, Léon; Hellin, A. C.; Jamar, Michelle ULg et al

in Genetic Counseling (Geneva, Switzerland) (2007), 18(2), 201-207

We report a 10-years-old female patient with a partial trisomy 18q and monosomy 11q due to a maternal translocation. The phenotype of our proband is partially common with Jacobsen syndrome and duplication ... [more ▼]

We report a 10-years-old female patient with a partial trisomy 18q and monosomy 11q due to a maternal translocation. The phenotype of our proband is partially common with Jacobsen syndrome and duplication 18q but she has also some atypical anomalies such as precocious puberty, a retinal albinism and hypermetropia. Based on cytogenetics and FISH analysis, the karyotype of the proband was 46,XX,der(11)t(11;18)(q24;q13). To the best of our knowledge, this is the first report of precocious puberty associated with either dup(18q) or del(11q) syndromes. [less ▲]

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See detailPreconditioning and protection against ischaemia-reperfusion in non-cardiac organs: a place for volatile anaesthetics?
Minguet, Grégory ULg; Joris, Jean ULg; Lamy, Maurice ULg

in European Journal of Anaesthesiology (2007), 24(9), 733-745

There is an increasing body of evidence that volatile anaesthetics protect myocardium against ischaemic insult by a mechanism termed 'anaesthetic preconditioning'. Anaesthetic preconditioning and ... [more ▼]

There is an increasing body of evidence that volatile anaesthetics protect myocardium against ischaemic insult by a mechanism termed 'anaesthetic preconditioning'. Anaesthetic preconditioning and ischaemic preconditioning share several common mechanisms of action. Since ischaemic preconditioning has been demonstrated in organs other than the heart, anaesthetic preconditioning might also apply in these organs and have significant clinical applications in surgical procedures carrying a high risk of ischaemia-reperfusion injury. After a brief review on myocardial preconditioning, experimental and clinical data on preconditioning in non-cardiac tissues will be presented. Potential benefits of anaesthetic preconditioning during non-cardiac surgery will be addressed. [less ▲]

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See detailPreconditioning of the tumor vasculature and tumor cells by intermittent hypoxia: implications for anti-cancer therapies
Martinive, Philippe ULg

Poster (2007, January)

Hypoxia is a common feature in tumors associated with an increased resistance of tumor cells to therapies. In addition to O(2) diffusion-limited hypoxia, another form of tumor hypoxia characterized by ... [more ▼]

Hypoxia is a common feature in tumors associated with an increased resistance of tumor cells to therapies. In addition to O(2) diffusion-limited hypoxia, another form of tumor hypoxia characterized by fluctuating changes in pO(2) within the disorganized tumor vascular network is described. Here, we postulated that this form of intermittent hypoxia promotes endothelial cell survival, thereby extending the concept of hypoxia-driven resistance to the tumor vasculature. We found that endothelial cell exposure to cycles of hypoxia reoxygenation not only rendered them resistant to proapoptotic stresses, including serum deprivation and radiotherapy, but also increased their capacity to migrate and organize in tubes. By contrast, prolonged hypoxia failed to exert protective effects and even seemed deleterious when combined with radiotherapy. The use of hypoxia-inducible factor-1alpha (HIF-1alpha)-targeting small interfering RNA led us to document that the accumulation of HIF-1alpha during intermittent hypoxia accounted for the higher resistance of endothelial cells. We also used an in vivo approach to enforce intermittent hypoxia in tumor-bearing mice and found that it was associated with less radiation-induced apoptosis within both the vascular and the tumor cell compartments (versus normoxia or prolonged hypoxia). Radioresistance was further ascertained by an increased rate of tumor regrowth in irradiated mice preexposed to intermittent hypoxia and confirmed in vitro using distinctly radiosensitive tumor cell lines. In conclusion, we have documented that intermittent hypoxia may condition endothelial cells and tumor cells in such a way that they are more resistant to apoptosis and more prone to participate in tumor progression. Our observations also underscore the potential of drugs targeting HIF-1alpha to resensitize the tumor vasculature to anticancer treatments. PMID: 17178869 [PubMed - indexed for MEDLINE] [less ▲]

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See detailPreconditioning of the Tumor Vasculature and Tumor Cells by Intermittent Hypoxia: Implications for Anticancer Therapies
Martinive, Philippe ULg; DEFRESNE, Florence; BOUZIN, Caroline et al

in Cancer Research (2006), 66(24), 11736-44

Hypoxia is a common feature in tumors associated with an increased resistance of tumor cells to therapies. In addition to O2 diffusion–limited hypoxia, another form of tumor hypoxia characterized by ... [more ▼]

Hypoxia is a common feature in tumors associated with an increased resistance of tumor cells to therapies. In addition to O2 diffusion–limited hypoxia, another form of tumor hypoxia characterized by fluctuating changes in pO2 within the disorganized tumor vascular network is described. Here, we postulated that this form of intermittent hypoxia promotes endothelial cell survival, thereby extending the concept of hypoxia-driven resistance to the tumor vasculature. We found that endothelial cell exposure to cycles of hypoxia reoxygenation not only rendered them resistant to proapoptotic stresses, including serum deprivation and radiotherapy, but also increased their capacity to migrate and organize in tubes. By contrast, prolonged hypoxia failed to exert protective effects and even seemed deleterious when combined with radiotherapy. The use of hypoxia-inducible factor-1α (HIF-1α)–targeting small interfering RNA led us to document that the accumulation of HIF-1α during intermittent hypoxia accounted for the higher resistance of endothelial cells. We also used an in vivo approach to enforce intermittent hypoxia in tumor-bearing mice and found that it was associated with less radiation-induced apoptosis within both the vascular and the tumor cell compartments (versus normoxia or prolonged hypoxia). Radioresistance was further ascertained by an increased rate of tumor regrowth in irradiated mice preexposed to intermittent hypoxia and confirmed in vitro using distinctly radiosensitive tumor cell lines. In conclusion, we have documented that intermittent hypoxia may condition endothelial cells and tumor cells in such a way that they are more resistant to apoptosis and more prone to participate in tumor progression. Our observations also underscore the potential of drugs targeting HIF-1α to resensitize the tumor vasculature to anticancer treatments. (Cancer Res 2006; 66(24): 11736-44) [less ▲]

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See detailThe Precthl's method for neurological examination of neonates
Battisti, Oreste ULg

Learning material (2005)

This lecture by video explains the method and presents samples of normal and abnormal states of neonates according to the neurological examination by the stidu of general movements of newborns

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See detailLes précurseurs d'ozone dans le secteur tertiaire
Romain, Anne-Claude ULg; Nicolas, Jacques ULg

Report (2008)

Une enquête réalisée par le laboratoire TAUW à la demande de la chambre de commerce a été menée sur un certain nombre d'entreprises du secteur tertiaire dans la province de Luxembourg(coiffeurs ... [more ▼]

Une enquête réalisée par le laboratoire TAUW à la demande de la chambre de commerce a été menée sur un certain nombre d'entreprises du secteur tertiaire dans la province de Luxembourg(coiffeurs, imprimeries, nettoyage, ...). Cette enquête portait sur une tentative d'évaluation des composés précurseurs d'ozone (solvants, ...). L'ULg a été chargée de l'analyse des résultats. Ceux-ci restent encore très partiels et ne donne pas de tendance précise pour la province. [less ▲]

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See detailPrecursor Gas Measurements (Chapter 2)
Notholt, J.; Bingemer, H.; Berresheim, H. et al

in Thomason, Larry W.; Peter, Thomas (Eds.) Assessment of Stratospheric Aerosol Properties (2006)

Assessments of stratospheric ozone have been conducted for nearly two decades and have evolved from describing ozone morphology to estimating ozone trends, and then to attribution of those trends ... [more ▼]

Assessments of stratospheric ozone have been conducted for nearly two decades and have evolved from describing ozone morphology to estimating ozone trends, and then to attribution of those trends. Stratospheric aerosol has only been integrated in assessments in the context of their effects on ozone chemistry and has not been critically evaluated itself. As a result, the Assessment of Stratospheric Aerosol Properties (ASAP) has been carried out by the WCRP project on Stratospheric Process and their Role in Climate (SPARC). The objective of this report is to present a systematic analysis of the state of knowledge of stratospheric aerosols including their precursors. It includes an examination of precursor concentrations and trends, measurements of stratospheric aerosol properties, trends in those properties, and modeling of aerosol formation, transport, and distribution in both background and volcanic conditions. The scope of this report is extensive; however, some aspects of stratospheric aerosol science have been deliberately excluded. For instance, we have not attempted to include an examination of polar stratospheric clouds (PSCs) or other clouds (such as cirrus clouds) occurring at or above the tropopause except in as much as they influence aerosol observations. Polar stratospheric clouds are the subject of a separate SPARC activity. We have produced a gap-free aerosol data base for use beyond this report. This required some new analysis that has not previously appeared in the technical literature. Similarly, the trend analysis required the development of a new analysis technique that is the subject of an article published in the Journal of Geophysical Research. New work is clearly identified in the present report. [less ▲]

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See detailThe precursor of a psychrophilic alpha-amylase: structural characterization and insights into cold adaptation
Claverie, P.; Vigano, C.; Ruysschaert, J. M. et al

in Biochimica et Biophysica Acta-Proteins and Proteomics (2003), 1649(2), 119-122

The alpha-amylase precursor from the bacterium Pseudoalteromonas haloplanktis possesses a propeptide at the C-terminus possibly responsible for outer membrane translocation. Unlike the predicted beta ... [more ▼]

The alpha-amylase precursor from the bacterium Pseudoalteromonas haloplanktis possesses a propeptide at the C-terminus possibly responsible for outer membrane translocation. Unlike the predicted beta-barrel of autotransporters, this C-terminal propeptide displays a noticeable alpha-helix content. It is connected to the enzyme by a disordered linker and has no significant interaction with the catalytic domain. The microcalorimetric pattern of the precursor also demonstrates that the stability of protein domains may evolve differently. (C) 2003 Elsevier B.V. All rights reserved. [less ▲]

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See detailThe Precursor of the Streptomyces R61 Dd-Peptidase Containing a C-Terminal Extension Is Inactive
Fanuel, Laurence; Granier, Benoît; Wilkin, Jean-Marc et al

in FEBS Letters (1994), 351(1), 49-52

The Streptomyces R61 DD-peptidase gene encodes a 26-residue C-terminal extension which is not found in the mature protein. When the gene was expressed in Escherichia coli, the extension was not cleaved ... [more ▼]

The Streptomyces R61 DD-peptidase gene encodes a 26-residue C-terminal extension which is not found in the mature protein. When the gene was expressed in Escherichia coli, the extension was not cleaved and the precursor protein was not enzymatically active. It also reacted with penicillins significantly more slowly than the mature protein. The introduction of a 'stop' codon after that corresponding to the C-terminal residue of the mature protein resulted in the production of an active protein in the periplasm of E. coli. [less ▲]

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See detailPrecursors and avalanches in a monolayer of spherical grains
Lumay, Geoffroy ULg

Conference (2006, June)

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See detailPrecursors to avalanches in a granular monolayer
Scheller, T.; Huss, C.; Lumay, Geoffroy ULg et al

in Physical Review E (2006), 74(3, Pt 1), 31311

We investigate the stability of a granular monolayer composed of spherical grains on an inclined plate. When the tilt angle alpha increases, some reorganizations are observed throughout the pile. The ... [more ▼]

We investigate the stability of a granular monolayer composed of spherical grains on an inclined plate. When the tilt angle alpha increases, some reorganizations are observed throughout the pile. The packing fraction rho of the packing evolves by successive jumps. Those discontinuous events precede the collapse of the pile at a critical angle alphac. The occurrence of precursors before avalanches is modeled by stop-and-go motions of blocks due to the competition between sliding friction and the Janssen effect [J. Durand, (Springer-Verlag, New York, 2000)]. [less ▲]

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See detailLa prédation
Sibony, Anne-Lise ULg

Conference (2009, December 09)

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See detailPredatory boreholes in Tournaisian (Lower Carboniferous) spiriferid brachiopods
Mottequin, Bernard ULg; Sevastopulo, George

in Lethaia (2009), 42

A brachiopod fauna from the uppermost part of the Tournaisian Tournai Formation (Belgium) contains an undetermined species of Crurithyris (Spiriferida, Ambocoeliidae), which displays numerous bored shells ... [more ▼]

A brachiopod fauna from the uppermost part of the Tournaisian Tournai Formation (Belgium) contains an undetermined species of Crurithyris (Spiriferida, Ambocoeliidae), which displays numerous bored shells. About 8% of the 432 specimens with conjoined valves display single, small (≤ 1 mm) boreholes, which are smooth-sided, cylindrical or weakly conical, circular to slightly elliptical in plan view, perpendicular to the shell surface and generally complete. Of the 35 bored articulated specimens, 27 were drilled on the ventral valve. Most of the boreholes are located in the posterior half of the shell, and no case of edge-drilling has been observed. The boreholes were drilled by a predator, or possibly a parasite, which selected individuals greater than 2.5 mm long. Crurithyris sp. may have represented an attractive (in terms of energy cost) and easy target for a small-sized predator because of its thin shell and ornament of minute spines. [less ▲]

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See detailPredatory boreholes in Tournaisian (Lower Carboniferous) spiriferid brachiopods
Mottequin, Bernard ULg; Sevastopulo, George

in Budd, G. E.; Streng, M.; Daley, A. C. (Eds.) et al Programme with abstracts of the 51st Palaeontological Association Annual Meeting (2007, December)

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See detailPredatory hoverflies select their oviposition site according to aphid host plant and aphid species
Almohamad, Raki; Verheggen, François ULg; Francis, Frédéric ULg et al

in Entomologia Experimentalis et Applicata (2007), 125(1), 13-21

The hoverfly Episyrphus balteatus De Geer (Diptera: Syrphidae) is an abundant and efficient aphid-specific predator. Several aphidophagous parasitoids and predators are known to respond positively to ... [more ▼]

The hoverfly Episyrphus balteatus De Geer (Diptera: Syrphidae) is an abundant and efficient aphid-specific predator. Several aphidophagous parasitoids and predators are known to respond positively to aphid-infested plants. Semiochemicals from the latter association usually mediate predator/parasitoid foraging behavior toward sites appropriate for offspring fitness. In this study, we investigated the effect of aphid host plant and aphid species on foraging and oviposition behavior of E. balteatus. Behavioral observations were conducted using the Noldus Observer v. 5.0, which allows observed insect behavior to be subdivided into different stages. Additionally, the influence of aphid species and aphid host plant on offspring fitness was tested in a second set of experiments. Acyrthosiphon pisum Harris and Megoura viciae Buckton were equally attractive for E. balteatus whereas Aphis fabae Scopoli (all Homoptera: Aphididae) were less attractive. These results were correlated with (i) the number of eggs laid, which was significantly higher for the two first aphid species, and (ii) the fitness of hoverfly larvae, pupae, and adults. Two solanaceous plant species, Solanum nigrum L. and Solanum tuberosum L. (Solanaceae), which were infested with Myzus persicae Sulzer (Homoptera: Aphididae), were also compared using the same approach. Discrimination between these two M. persicae host plants was observed, with S. tuberosum being preferred as an oviposition site by the predatory hoverfly. Larval and adult fitness was correlated with the behavioral observations. Our results demonstrated the importance of the prey-host plant association on the choice of the oviposition site by an aphid predator, which is here shown to be related to offspring fitness. [less ▲]

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See detailPredegenerated Nerve Allografts Versus Fresh Nerve Allografts in Nerve Repair
Dubuisson, A. S.; Foidart-Dessalle, Marguerite ULg; Reznik, Michel ULg et al

in Experimental Neurology (1997), 148(1), 378-87

This study reevaluated the possibility of using predegenerated nerves as donor nerve allografts for nerve repair and compared the results of functional recovery to those obtained after standard, fresh ... [more ▼]

This study reevaluated the possibility of using predegenerated nerves as donor nerve allografts for nerve repair and compared the results of functional recovery to those obtained after standard, fresh nerve allograft repair. Twenty donor rats underwent a ligature/ section of the left sciatic nerve 4 weeks before nerve graft harvesting. Forty recipient rats underwent severing of the left sciatic nerve leaving a 15-mm gap between the nerve stumps. Graft repair was undertaken using either the predegenerated left sciatic nerve of the 20 donor rats (predegenerated group, 20 recipient rats) or the normal right sciatic nerve of the 20 donor rats (fresh group, 20 recipient rats). Recovery of function was assessed by gait analysis, electrophysiologic testing and histologic studies. Walking tracks measurements at 2 and 3 months, electromyography parameters at 2 and 3 months, peroperative nerve conduction velocity and nerve action potential amplitude measurements at 3 months, as well as assessments of myelinated nerve fiber density and surface of myelination showed that fresh and predegenerated nerve grafts induced a comparable return of function although there was some trend in higher electrophysiologic values in the predegenerated group. The only slight but significant difference was a larger mean nerve fiber diameter in the nerve segment distal to a predegenerated nerve graft compared to a fresh nerve graft. Although our study does not show a dramatic long-term advantage for predegenerated nerve grafts compared to fresh nerve grafts, their use as prosthetic material is encouraging. [less ▲]

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