Also, since the composition of Gibco hESFM used in the initial method is not reported in the literature, it appeared worthwhile to test simpler growth media (DMEM) supplemented with hydrocortisone. To optimise the isolation of brain microvessels, special attention was given during initial isolation to removing all meninges (including inside sulci) and most of

white matter, and this led to increased culture purity, with fewer contaminating cells growing out from the isolated vessel fragments. The extra time taken over the preparation, while slightly reducing yield, resulted in purer cultures. To reduce the ‘edge effects’ caused by leak of current around the edges of the monolayer at the circumference of the insert, larger inserts were used (12 mm diameter, hence smaller circumference:surface area ratio).

In the first series of experiments (Fig. 3A), TEER of cells grown in normal PBEC medium peaked at ∼100 Ω cm2 Ion Channel Ligand Library high throughput at 2 days and then declined. A similar pattern was seen in cells grown in PBEC medium or medium without serum, but supplementation at 48 h by adding hydrocortisone and increasing cAMPi increased peak resistance to ∼400 Ω cm2 in serum-free medium and to ∼530 Ω cm2 in serum-containing medium; in supplemented medium, especially medium containing serum, the high resistance phase lasted longer than in normal PBEC medium (Fig. 3B). Puromycin treat-ment was introduced to kill pericytes (Perrière et al., 2005). Addition of 4 µg/mL Proteases inhibitor puromycin in the first three days of growth led to a significant further improvement in purity triclocarban of the PBEC culture and a significant increase in TEER. In addition, using BPDS rather than foetal calf serum (FCS) in the culture medium also increased TEER (Fig. 4). To reduce variability of TEER observed with the STX2 chopstick electrodes, the

WPI Endohm chamber system was used, with large concentric plate electrodes above and below the insert. TEER of 485–1300 Ω cm2 (Fig. 5) was typically obtained (mean TEER=789±18 Ω cm2; n=91 inserts), with good reproducibility between vials ( Fig. 6) and batches. Furthermore, the corresponding TEER and Papp values from each batch confirm the reliability of the model, showing high TEER correlated with low [14C]suc-rose permeability ( Fig. 7). Mean Papp for [14C]sucrose was 5.7±0.7×10–6 cm/s (n=7 experiments, 3 inserts each). Further functional characterisation of this phase of the porcine BBB model is described in detail elsewhere ( Patabendige et al., this issue). Pericyte contamination was reduced by differential trypsinisation during passaging the cells before seeding onto inserts and DMEM was used with ACM (i.e. DMEM/ACM). Confluent monocultures of PBECs had an elongated cobblestone-shaped morphology, although not generally so clearly spindle-shaped as reported for rat and bovine brain endothelial cell cultures.

Taking into account the E.U. legislation, mousses WPC, MF–WPC, and I–WPC would be allowed to receive the comparative “increased” claim for the protein content (Table 5, Table 6 and Table 7). Among the standards for absolute nutrient content and comparative claims for protein, therefore, those adopted in the E.U. were the less restrictive for the mousse formulations evaluated. The Brazilian standards for absolute and comparative claims for the protein Selleck Epigenetic inhibitor content are proposed to change in the following aspects: for the conditions of “source” and “high”, food products must contain at least 6 g and 12 g of this nutrient per serving portion, respectively, and their amount of indispensable amino acids must fulfil the

requirements established by the FAO/WHO/UNU (2007) for adults in terms of mg amino acid per g protein; Obeticholic Acid molecular weight for the condition of “increased”, the reference product must fulfil the updated conditions for the claim “source”, the modified food products must present an

increase of at least 30% in the protein content per serving portion, and the amount of indispensable amino acids provided by their added protein must fulfil the requirements established by the FAO/WHO/UNU (2007) for adults in terms of mg amino acid/g protein (ANVISA, 2011). According to these conditions and the amino acid composition of the cow’s milk protein reported by FAO/WHO (1991), mousses WPC, MF–WPC, I–WPC, and MF–I–WPC could receive the claim “source” and none of the products could be allowed to receive the claims “high” and “increased” (Table 7). In this case, the proposed changes for the Brazilian legislation did not affect the classification of the products studied, either for

absolute or for comparative nutrient claims. Regarding dietary fibre, the current Brazilian legislation states that the claims “source” and “high” might be used if the solid or semi-solid product the presents a minimum of 3 g and 6 g per 100g of this nutrient, respectively (Brasil, 1998). The E.U. also adopts these classifications for dietary fibre content (EC, 2007). In the U.S., the claims “good source” and “high” for dietary fibre content follows the same requisites described later for the protein content (US CFR, 2010c). The same occurs with the comparative claims “increased” and “enriched” in the E.U. and the U.S., respectively, for dietary fibre content that follow the same requisites for the protein content (EC, 2007 and US CFR, 2010c). For the purpose of labelling in the U.S., a value of 25 g of TDF shall be the DRVs for adults and 4 years-old children or older (US CFR, 2010c). The “Increased” claim is currently used in Brazil for dietary fibre when there is an increase of 25% and a difference of 3 g of dietary fibre/100 g between the modified solid or semi-solid product and the original one (Brasil, 1998). Regarding the changes proposed in the Brazilian legislation, they include values of at least 2.

65; p = 0.002), whereas no benefit was seen in ERCC1-postive patients (HR 1.14; p = 0.40) [88].

Recently, however, Tacrolimus mouse this finding has been called into question due to the inability of currently available ERCC1 antibodies to detect the unique functional ERCC1 isoform [59]. Consequently, the usefulness of ERCC1 expression in guiding treatment for NSCLC patients is limited at present. Nevertheless, the results of several ongoing studies investigating tailored adjuvant therapy based on expression of other markers (e.g. EGFR mutations and thymidylate synthase) are eagerly awaited. Additionally, use of immunotherapy in the adjuvant setting is being evaluated in the MAGRIT (MAGE-A3 as Adjuvant, Non-Small Cell Lung Cancer Immunotherapy) trial. Gaining a better understanding of the biology of targeted agents and obtaining long-term toxicity data before investigation in the adjuvant setting is also likely to improve the success of adjuvant trials.

Advances have been made in NSCLC management over the last three decades leading to small increases in 5-year survival rates across Europe (2–7%) [91], [92], [93] and [94], though further improvements are needed. However, advances in understanding of the molecular biology of the Alisertib clinical trial disease will help in the identification of novel targeted agents and development of personalised strategies for the numerous small subsets of defined NSCLC, with progress in imaging and treatment delivery also likely to improve outcomes. Furthermore, it is hoped that implementation of some of the strategies identified

in this article will go some way to improving selleck chemicals llc the outlook for patients with NSCLC. Rolf Stahel has provided consultation, attended advisory boards and/or provided lectures for Astellas, Abbott Diagnostics, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Daiichi Sankyo, GSK, Hoffmann–La Roche, Eli Lilly, Merck Serono, Merrimack, Pfizer and Tesaro; Solange Peters has provided consultation, attended advisory boards and/or provided lectures for Astellas, Hoffmann–La Roche, Eli Lilly and Company, AstraZeneca, Pfizer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Merck Serono, Merrimack and Tesaro; Paul Baas has participated in advisory boards for Astellas, Merck Sharp & Dohme and Pfizer; Elisabeth Brambilla has participated the Roche Ventana Advisory Board; Federico Cappuzzo has participated in advisory boards and consultancy for Roche, Astellas, Pfizer and AstraZeneca; W.E.E.

240, p < .0001). As can be seen in Appendix B, there were no main effects (or indeed interactions) of lexical category Pexidartinib or semantic-abstractness on psycholinguistic properties of stimuli. This being the case, we were confident that brain activation

in contrasts focusing on lexical category and semantic-abstractness were free of ulterior confounding effects. The experimental word categories were dispersed among 200 filler words during presentation, with which they were matched in length (F(1, 359) = 1.006, p > .436), bigram (F(1, 359) = 1.679, p > .084) and trigram frequency (F(1, 359) = .868, p > .560). 120 hash marks, matched to word stimuli in length, acted as a low level visual baseline in contrasts. Adopting a paradigm previously employed for investigating lexicosemantic Bortezomib processing (e.g., Hauk et al. 2004; for review, see Pulvermüller et al. 2009), words written in lowercase letters were presented tachistoscopically while haemodynamic responses were recorded using event-related fMRI. This passive reading paradigm was chosen to be unbiased

towards semantic or grammatical processing. Despite no overt instructions for semantic processing, it is reliably known to evoke early differential activations that reflect a word’s semantic category (see Hauk et al., 2008, for review), strongly implying that reading automatically evokes semantic processing of word stimuli in typical participants. Subjects were instructed to attend to and carefully read all stimulus words silently, without moving their lips or tongue. The passive reading task was delivered in three blocks of approximately 7 min each. A short presentation time of 150 ms ensured that saccades were discouraged and that participants had to continuously attend to the screen in order to perform the task. A central fixation cross was displayed between stimuli for an average 2350 ms, with a jitter of ±250 ms, resulting in SOAs

between 2250 and 2750 ms (average 2500 ms). The order of stimuli was pseudo-randomised (restriction: not more than two items of the same category in direct succession) with two lists, counter-balanced across subjects. Following the scan, our participants were requested to complete a short unheralded word recognition test outside the scanner. In the recognition test, they were presented SPTLC1 with a list of experimental stimuli and novel words and had to rate each word on a scale from 1 to 7, indicating how certain they were that a given item had appeared in the fMRI experiment. For evaluation, ratings were converted into percentage correct/incorrect responses. The test contained a combination of 50 experimental and 25 novel distracter words, and above chance performance was thus taken to confirm that subjects had engaged with the task. A Siemens 3T Tim Trio (Siemens, Erlangen, Germany) with a head coil attached was employed during data collection.

Surface currents were recorded as moving to the east and north in July–August 2006, with velocities ranging from 20 to 30 cm/s in water temperatures as high as 30 °C (Coppini et al., 2011). The high-frequency SKIRON wind forecast system showed winds varying this website from north-westerly to south-westerly, a pattern that remained steady for most of the summer of 2006, with wind strength varying between 2 and 7 m/s

(Lardner et al., 2006). For these meteorological and oceanographic conditions, oil spill impacts on shoreline regions were observed to be heaviest from Jieh up to south of Beirut, i.e., closer to the spill source. Significant impacts between Beirut and Chekka and northward along the Syrian coast were also reported, and subsequently confirmed several weeks after the oil spill event (Coppini

et al., 2011). Adler and Inbar (2007) found that sandy shorelines show moderate to low susceptibility to oil spills in areas exposed to significant wave and wind action, i.e., with important natural cleaning processes. PLX4032 mw Regions with the lower shoreline susceptibility in Israel comprise relatively straight and smooth profiles without deep and complex bays and headlands, preferably low, flat and sandy in nature (Adler and Inbar, 2007). Shoreline susceptibility increases in Israel, and throughout the Mediterranean Sea, with the presence of important ecosystems, specific habitats, coastal resources and shoreline types that must be preserved in case of oil spills. A contrasting setting is that associated Reverse transcriptase with oil refineries. In Syria and Lebanon, oil refineries were found to be a controlling factor to As and Cr values in seafloor sediment regardless of local wave and meteorological conditions (Othman et al., 2000). Arsenium and Chromium were found to be

above natural levels offshore Syria, whereas elements such as Al, Ca, Fe, K, Mg, Mn, Na, Ba and Br and some trace metals (Pb, Zn and Cu) were naturally cleaned and kept under defined limits in the same region. This poses the interesting problem of secondary pollutants in oil spills and, particularly, in industrial (chemical) spills that occur during drilling operations. In this latter case, the North Sea is one of the best documented regions in the literature, and where drilling muds contaminated with hydrocarbons and heavy metal elements are known to be an important polluter (Davies et al., 1984 and Grant and Briggs, 2002). Here, hydrocarbon concentration levels were found to be as much as 1000 times normal background levels close to drilling platforms (i.e., at distances < 250 m), but show a rapid decline with distance (Davies et al., 1984). Background levels were found to be reached some 2000–3000 m from the platform, with the shape and extent of polluted zones being largely determined by current regimes and scale of the drilling operations (Davies et al., 1984 and Elliot, 1986).

Lesions otherwise suited to brachytherapy for management of the primary tumor may present with early adenopathy or require sentinel lymph node evaluation or inguinal node dissection. A combined approach of brachytherapy for the primary and surgical evaluation of lymph nodes can be considered. T3 tumors with extension into the penile Cell Cycle inhibitor urethra are

generally not optimal candidates for brachytherapy, although those cases where urethroscopy reveals submucosal deformity without mucosal disruption may still be treated with success, although there is however an increased risk of meatal stenosis that should be explained and understood by the patient. If a locally advanced primary tumor presents with concomitant adenopathy, brachytherapy is unlikely to play a role in management and combinations of external beam radiotherapy (EBRT) with chemotherapy ± surgery should be considered (18). Tumor grade is not an exclusion factor for brachytherapy (19). In the 74 cases treated by Crook et al. (19) between 1989 and 2007, half had well-differentiated and the other half had moderately or poorly differentiated cancer. Moderately and poorly differentiated tumors responded as well as those that were well differentiated. Local recurrences occurred in six well-differentiated

and two moderate-to-poorly differentiated cases. Penile click here brachytherapy is not a treatment modality that needs to be available in every radiotherapy department. A high volume and varied brachytherapy practice that undertakes interstitial Pyruvate dehydrogenase brachytherapy for other tumor sites may wish to provide this treatment as the basic principles are not dissimilar to those for other interstitial implants. As this is an uncommon tumor, three to six cases per year are sufficient to justify a program. Collaboration

with a penile carcinoma center of excellence is recommended. Penile brachytherapy can be performed under general anesthesia or penile block with systemic sedation. Antibiotic prophylaxis is optional. Low-dose-rate (LDR) brachytherapy consists of either manually afterloaded 192Ir or pulse-dose-rate (PDR) brachytherapy. The latter uses automated afterloading with a high-intensity 192Ir source to deliver hourly pulses. The two are similar in implant principles and total dose. These implants should be clinically designed according to the anatomic extent of tumor. Knowledge of the Paris system of dosimetry (20) as shown in Fig. 1 is a helpful guide for placement of sources so that the prescription isodoses will encompass the visible and palpable tumor with an appropriate margin. Because the depth of invasion is often underappreciated, margins should be generous and of 10 mm or greater in all directions around the gross tumor volume to delineate the clinical target volume.

In fact, the second-best BLASTX hit, after BgP, is to a Eubacterium acidaminophilum FdhC (CAC39240.1) that has been characterized experimentally ( Graentzdoerffer et al., 2003). Formate could serve as an electron donor, carbon substrate, or both. A possible formate dehydrogenase gamma subunit gene (01341_2381) is found in a cluster with other ORFs

variously annotated as formate, thiosulfate, Epacadostat cost and tetrathionite reductase component genes; it is doubtful whether their in vivo roles can be deduced from the sequences alone. Phosphotransferase systems for carbohydrate uptake typically consist of one or two membrane (EIIC/EIID) and one or two cytosolic (EIIA/EIIB) components specific for a given carbohydrate, and two more general cytoplasmic components (EI and HPr), which may be in various combinations of fused and separate proteins (reviewed in Deutscher et al. (2006)). EI is a phosphoenolpyruvate:protein phosphotransferase, and HPr is a phosphocarrier transferring phosphate groups from EI to EIIA. In Gram-negative bacteria, phosphate groups are transferred in a cascade from phosphoenolpyruvate (PEP) to the membrane PTS components, and thence to a periplasmic carbohydrate

molecule, concomitant with its uptake. The phosphorylated carbohydrates are typically fed into the glycolysis pathway. PTS genes are also involved in transcriptional regulation of carbohydrate metabolism. Thalidomide Only two sets

CYC202 supplier of putative PTS-related genes have been annotated in the BOGUAY genome. One is related to ascorbate uptake systems, and includes possible EIIA (ulaC, 00136_0633), EI (ptsI, 00136_0635) and HPr (hprK, 00136_0634) genes; the other is related to regulatory systems that are thought to coordinate nitrogen and carbon uptake, and includes putative EIIA (ptsN, 00726_1444) and HPr (hprK, 00726_1445) genes. No membrane-protein genes have been identified for either of these potential PTS systems, however; they may have strictly regulatory (or other) functions, or novel membrane components. The BOGUAY genome encodes a complete glycolytic pathway, and apparently two types of energy-generating electron transport pathways. In addition to the common oxidative phosphorylation pathway, in several possible variants, it possesses two different genes for most components of a putative Rnf complex, a potentially energy-generating ion pump whose detailed function is not yet well understood. This suggests that the BOGUAY strain may be able to access a range of electron donors and acceptors. Details are discussed immediately below. All glycolysis genes seem to be present in the BOGUAY genome (Table S6), with energy-conserving pyrophosphate-consuming enzymes apparently preferred to those hydrolyzing ATP. There are two possible pyrophosphate-dependent 6-phosphofructokinases (PFKs; Fig.

CAT (EC 1.11.1.6; CAT) activity was evaluated by observing the rate of decrease in hydrogen peroxide (H2O2) absorbance in a spectrophotometer at 240 nm. SOD (EC 1.15.1.1, SOD) activity was assessed by quantifying the inhibition of superoxide-dependent adrenaline auto-oxidation in a spectrophotometer at 480 nm (Aebi, 1984 and Misra and Fridovich, 1972). CAT activity is expressed as units CAT/mg protein and SOD activity as Units SOD/mg protein. To better understand the effect of vitamin A supplementation upon these free radical-detoxifying enzymes we applied a ratio between SOD and CAT activities (SOD/CAT), two enzymes that work in sequence to reduce the superoxide

anion to water. BMS-354825 in vivo Glutathione S-transferase (GST, E.C. 2.5.1.18) activity was determined spectrophotometrically at 340 nm by measuring the formation of the conjugate of IGF-1R inhibitor GSH (glutathione) with CDNB (chloro-dinitro benzene) as previously described

by Habig and Jakoby (1981). Enzyme activity was determined by mixing buffer GSH 20 mM with the sample. The reaction started by CDNB 20 mM addition was carried out at 30 °C, and monitored spectrophotometrically for 3 min. Corrections of the spontaneous reaction were made by measuring and subtracting the rate in the absence of enzyme. Results are expressed as nmol of CDNB conjugated with glutathione/min/mg protein. Body weights, body weight gains, gestation length, numbers of implants and pups delivered, delivery index and viability indices of pups were analyzed by the one-way analysis of variance (ANOVA) to determine if any statistical differences existed among the groups. If the ANOVA presented a significant result, Dunnett’s test was

performed to detect any significant differences between the treated groups and their corresponding controls. The litter was used as a unit for statistical Coproporphyrinogen III oxidase evaluation for the data of body weights and viability index of pups. The sex ratios of pups were analyzed by Chi2 test. Differences in OFT scores and biochemical parameters in hippocampi and striatum between control and retinyl palmitate treated dams were determined with one-way ANOVA. For post-hoc comparisons, the Duncan’s test was conducted. The number of correct and incorrect performances in the homing test was compared among groups using a Chi2 test. A two-way (ANOVA), with drug exposure and sex difference as factors, was used to analyze differences in the time spent over the homing area, differences in OFT scores and biochemical parameters in offspring hippocampus and striatum. For post-hoc comparisons, the Bonferroni test was conducted when exposure factor was significantly and one-way ANOVA with Tukey’s post hoc comparisons when sex difference was significantly different among groups. For the time spent over the homing area, OFT scores and biochemical analysis the litter was used as a unit for statistical evaluation with distinction between males and females. Both behavioral and biochemical results are expressed as means ± standard error of the mean (S.

The histopathological examination revealed

acute inflammation. Complete reversibility of all changes was found one week after exposure ( Cho et al., 2007). These cytokines and chemokines can activate NALP3, a member of the cytoplasmic Nod-like receptor family that regulates the activity of Caspase-1 via formation of the inflammasome. Activated Caspase-1 triggers the cleavage of pro-inflammatory cytokines (IL-1beta and IL-18) for subsequent activation and secretion, which is likely to be part of the pathway leading to silicosis. However, there is no in vivo correlate for this pathway, as Obeticholic Acid in vitro SAS is not involved in progressive fibrosis or silicosis of the lung. High doses of SAS may however indeed result in acute pulmonary inflammatory responses. Apoptosis was not found in A549 and rat alveolar cells up to a concentration of 100 ppm SAS. Treatment of ICR mice by single intraperitoneal injection of 50, 100 or 250 mg/kg of pyrogenic silica (average primary particle size 12 nm) caused

increased blood levels of IL-1beta and TNF-alpha, and increased nitric SP600125 supplier oxide release from peritoneal macrophages. Ex vivo, cultured peritoneal macrophages harvested from the treated mice showed the expression of inflammation-related genes (IL-1, IL-6, TNF-alpha, inducible nitric oxide synthase, cyclooxygenase 2). In the spleen, the relative distribution of natural killer cells and T cells was increased 184.8% and 115.1%, respectively, as compared with control animals, and that of B cells was decreased to 87.7% ( Park and Park, 2009). Gene expression profiles after exposure to amorphous silica particles were studied in human epidermal keratinocytes (HaCaT cells) (Yang et al., 2010; see Table 2 for particle characterisation). At 10 mg/L – the only reported, slightly

cytotoxic concentration–a downregulation of oxidative-stress associated proteins (Prx1, Prx6, Trx, GSTP1) may indicate a reduced antioxidant capacity following the induction of cytotoxicity by particle exposure. Similarly, changes in molecular chaperones Edoxaban and energy metabolism-associated proteins were indications for silica-induced cytotoxicity. The typical alterations of apoptotic marker proteins were not found. Cytoskeleton-associated proteins (keratin 9, keratin 4) were upregulated and may represent a compensatory stress response. The cascade of key events causing toxicity after SAS exposure, i.e., the mode of action (MOA) of SAS and its relevance are summarised in Table 3. SAS may interact with blood cells. In vitro, haemolysis and clotting of cells has been found in the presence of hydrophilic SAS. In vivo, intravenous or intraperitoneal injections of mesoporous silica particles caused the death of laboratory animals, probably by pulmonary embolism.

Biopsy showed invasive adenocarcinoma. Patients with ulcerative

colitis are recommended to have surgery when a colonic stricture is found. The authors thank Drs. Shinji Tanaka, Ronald Yeh, and Hazem Hammad for their generous contributions. “
“Des erreurs se sont glissées dans la liste des auteurs du PO 26 du supplément au volume 47, 2012 du Pharmacien Hospitalier et Clinicien. Il fallait signaling pathway lire : L. Soubraa, F. el Masria, S. Doumiatia, S. Kabbanib aPharmacology and clinical pharmacy department, Beirut Arab university, Beirut bFaculty of medicine, Lebanese American University, Beirut Nous prions les auteurs et nos lecteurs de nous excuser pour cette erreur. “
“La référence bibliographique du résumé C001 « Applicabilité du GPS dans l’évaluation des limitations à la marche des claudications artérielles » (dx.doi.org/10.1016/j.jmv.2014.07.037) est la suivante : Gernigon M, Le Faucheur A, Noury-Desvaux B, Mahe G, Abraham P ; Post-GPS Study Coinvestigators Group. Applicability of global positioning system for the assessment of walking ability in patients with arterial claudication. J Vasc Surg. 2014;60:973–81. Veuillez nous excuser pour cette erreur. “
” photo Axel Perez/Pleine ouverture Jean-Daniel Picard nous a quittés le 16 décembre 2013. Quelques semaines avant son décès qu’il estimait proche, il m’avait fait parvenir ce qu’il appelait son Journal

où il rappelait les étapes essentielles de sa vie. Jean est né dans une famille juive alsacienne qui était devenue allemande en 1871. Son père, né en Alsace allemande en 1887, avait 8 fils qui normalement auraient dû aller faire leur Daporinad cost service militaire en Allemagne, mais tous préférèrent s’expatrier et se retrouvèrent en Suisse. Le père de Jean commença des études à l’École horlogère Idelalisib research buy de la Chaux-de-Fonds, mais ce travail trop immobile n’était pas fait pour lui. Il se lança dans plusieurs métiers et en définitive devint voyageur de commerce. Quelques années plus tard, il était

devenu un importateur très réputé de vins français, spécialement de Bourgogne, en Suisse. Il se maria à l’âge de 35 ans avec une jeune française modeste dont la mère tenait une mercerie rue de Beaune à Paris. Jean naquit à Lausanne en 1927 puis, pour des raisons essentiellement familiales, ses parents sont revenus vivre à Paris tandis que son père continuait son commerce en Suisse. Jean commença sa scolarité primaire à Paris et ses études secondaires au Collège Chaptal. Puis, la guerre entre la France et l’Allemagne se déclencha et la famille ne put rentrer en Suisse qui avait fermé ses frontières. Tous ses membres se retrouvèrent en Bourgogne alors que Jean allait en bicyclette au lycée de Beaune, mais il avait toujours considéré cette obligation comme une partie de plaisir. La guerre se poursuivant, la famille partit se réfugier à Lyon où Jean continua le lycée. Mais ils furent dénoncés et ce fut la fuite vers le Mont-Dore en Auvergne, puis à Perpignan.