No description available.

Molecular engineering of donor-acceptor dyads and multimodular systems to control the yield and lifetime of charge separation is one of the key goals of artificial photosynthesis for harvesting sustainably solar energy. The design of the donor-acceptor systems mimic a part of green plants and bacterial photosynthetic processes. The photochemical events in natural photosynthesis involve the capturing and funneling of solar energy by a group of well-organized chromophores referred to as an ‘antenna' system causing an electron transfer into the ‘reaction center,' where an electron transfer processes occur resulting a long-lived charge separated state. Over the last two to three decades, many efforts have been directed by the scientific community designing of multi-modular systems that are capable of capturing most of the useful sunlight and generating charge separated states of prolonged lifetimes with adequate amounts of energy. In this dissertation, we report on the design and synthesis of donor–acceptor conjugates with the goal of modulating the yield and lifetime of their charge separated states and hence, improving the conversion of light energy into chemical potential. In simple donor-acceptor systems, generally, the energy and electron transfer events originate from the singlet excited state of the donor or acceptor and can store the greatest amount of energy but must be fast to out compete intersystem crossing. To address this limitation, we have designed novel donor –acceptor conjugates that use high-energy triplet sensitizers in which electron transfer is initiated from the long lived triplet state of the donor. The triplet photosensitizers used were palladium(II) porphyrin and platinum(II) porphyrin. Heavy metal effect in these porphyrins promoted intersystem crossing and the energies of their excited state was quite high. For the case of palladium (II) porphyrin the energy stored was found to 1.89 eV and that of platinum(II) porphyrin 1.84 eV. In addition to using triplet photosensitizers as donors, we have used donors that are difficult to oxidize and hence producing long lived charge separated states with adequate amount of stored energy. The system that was used for this study is zinc porphyrin with meso-aryl pentafluorophenyl substituents and fullerene, C60 as the acceptor. The presence of fluorine substituents on zinc porphyrin makes it harder to undergo oxidation. When this high potential donor-acceptor system undergoes a photoinduced charge-separation, the estimated energy stored was found to be 1.70 eV, one of the highest reported in literature so far. To further extend the lifetime of the charge separated states generated in this high-potential zinc porphyrin-fullerene dyad a pyridine functionalized tetrathiafulvalene was axially coordinated to the Zn metal producing a supramolecular triad capable of producing long-lived charge separated state. In a subsequent study, a multi-modular donor-acceptor system composed of a porphyrin, fullerene (C60) and a BF2-chelated dipyrromethene (BODIPY) with a supramolecular arrangement in the form of porphyrin-BODIPY-C60, one of the few reported in literature. By selectively exciting BODIPY and ZnP moieties, efficient singlet-singlet energy transfer from 1BODIPY * to ZnP in toluene was observed in the case of the dyad ZnP-BODIPY. However, when ZnP is excited, electron transfer occurred with the formation ZnP.+-BODIPY-C60.- charge separated state persisting for microseconds.

No description available.

In this thesis, we included results from two studies. The first one considered the effects of the blood volume changes, during blood donation, on the heart rate variability (HRV) measured, non-invasively, form electrocardiographic (ECG) and photoplethysmographic (PPG) signals. Our results showed that, during blood donation, there were no significant changes in the pulsatile area of PPG signal, while heart rate increased. No significant changes were noticed in HRV extracted from both signals. Error analysis between the HRV extracted from ECG and peak interval variability (PIV) suggested that the error during blood donation was increased which means that the use of PIV extracted from PPG signal, used as a replacement diagnostic tool in clinical applications, needs further investigations and should be carefully studied in non-stationary cardiovascular situations such as blood donation. The imbalance between the two branches of the autonomic nervous system, sympathetic and parasympathetic, vagal, may result in a harmful activation of myocardial tissues which cause arrhythmias and sudden cardiac death. Although the study of the sympathovagal balance have been attracting many researchers, further studies are needed to elucidate the effects of many kinds of drugs on the autonomic modulation of the cardiac muscle, specifically, the cells of sinoatrial (SA) node. The aim of the second part of this thesis was to assess the effects of calcium channel blocker (Verapamil), calcium channel sensitizer (Levosimendan), calcium chloride (CaCl2), the combinations of verapamil/ CaCl2, levosimendan/ CaCl2, and noradrenaline infusion on beat-to-beat cardiovascular variability represented, in this research, by systolic blood pressure variability (SBPV), and stroke volume variability (SVV) signals. We used Fat Fourier Transform (FFT) to evaluate the power spectral density of the fluctuations in both signals to evaluate the effects of short-term treatments with those drugs on the sympathovagal balance in normal rats. Then, we compared the spectra obtained from SBPV and SVV to decide which of these fluctuations along with corresponding spectrum was more able to provide a clear feedback about the autonomic nervous system. Our data suggests that there were a significant correlations between low- (LF), mid- (MF), and high-frequency (HF) spectra obtained from SBPV and SVV except between the HF spectra estimated from after the infusion of levosimendan where a poor correlation (r = 0.530, p = 0.281) was noticed. This that both HF components obtained provide different information regarding the autonomic nervous system modulation of the SA node cells, while the results obtained from the rest of experiments showed that both signals provide same information about the modulation of sympathetic and parasympathetic tone due to all stages of different drugs infusion studied in this thesis. Besides that, we found that both spectra may be used to track the fluctuations in the cardiac output as a result of the drugs infusion.

<p>One-step photoinitiated free radical carbonylation was employed for the rapid (5–7 min) labelling of aliphatic carboxylic acids, esters, and amides with a short-lived positron emitter ¹¹C (t_½ = 20.3 min) at the carbonyl position. The labelled compounds were synthesized from alkyl iodides (0.05–0.1 mmol), [¹¹C]carbon monoxide, and appropriate nucleophiles. Decay-corrected radiochemical yields were up to 74%; conversion of [¹¹C]carbon monoxide reached 85–90%; specific radioactivity was 158–192 GBq/mmol. The labelled compounds were identified and characterized using HPLC, LC-MS, and ¹H and ¹³C NMR. The effects of solvents, additives, photoirradiation, temperature, and reaction time were studied and discussed.</p><p>[<i>carbonyl-</i>¹¹C]Amides were synthesized using amines in 1–2 equiv. to iodides, exploiting solvent effects to control reactivity. [<i>carboxyl-</i>¹¹C]Acids were synthesized using water as a nucleophile, in binary and ternary aqueous solvent mixtures; the addition of TBAOH or KOH was necessary to obtain high radiochemical yields. [<i>carbonyl-</i>¹¹C]Esters were synthesized using primary and secondary alcohols, <i>tert-</i>butanol, and phenol. Bases were KOH, BuLi, LiHDMS.</p><p>The effects of photosensitizers were studied and exploited to accelerate the labelling of carboxylic acids and esters resulting in 75–85% decay-corrected radiochemical yields under mild conditions without the use of bases.</p><p>A mild procedure for the ¹¹C-carboxylation of alkyl iodides using DMSO as an oxygen nucleophile was developed. This method is expected to be suitable in the macroscale synthesis of carboxylic acids using isotopically unmodified carbon monoxide.</p><p>Radical carbonylation was applied to improve the synthesis of an extensively used PET tracer, [<i>carbonyl</i>-¹¹C]WAY-100635. The tracer was synthesized in one step, whereas a common approach via Grignard reagents requires three steps.</p><p>In addition, several (¹³C)compounds were synthesised using the described methods.</p><p>Free radical carbonylation may be used for the ¹¹C-carbonylation of alkyl iodides, whereas transition-metal carbonylation – of aryl halides and triflates. Thus, the two carbonylation methods are complementary with respect to the scope of synthetic targets.</p>

One-step photoinitiated free radical carbonylation was employed for the rapid (5–7 min) labelling of aliphatic carboxylic acids, esters, and amides with a short-lived positron emitter 11C (t½ = 20.3 min) at the carbonyl position. The labelled compounds were synthesized from alkyl iodides (0.05–0.1 mmol), [11C]carbon monoxide, and appropriate nucleophiles. Decay-corrected radiochemical yields were up to 74%; conversion of [11C]carbon monoxide reached 85–90%; specific radioactivity was 158–192 GBq/mmol. The labelled compounds were identified and characterized using HPLC, LC-MS, and 1H and 13C NMR. The effects of solvents, additives, photoirradiation, temperature, and reaction time were studied and discussed. [carbonyl-11C]Amides were synthesized using amines in 1–2 equiv. to iodides, exploiting solvent effects to control reactivity. [carboxyl-11C]Acids were synthesized using water as a nucleophile, in binary and ternary aqueous solvent mixtures; the addition of TBAOH or KOH was necessary to obtain high radiochemical yields. [carbonyl-11C]Esters were synthesized using primary and secondary alcohols, tert-butanol, and phenol. Bases were KOH, BuLi, LiHDMS. The effects of photosensitizers were studied and exploited to accelerate the labelling of carboxylic acids and esters resulting in 75–85% decay-corrected radiochemical yields under mild conditions without the use of bases. A mild procedure for the 11C-carboxylation of alkyl iodides using DMSO as an oxygen nucleophile was developed. This method is expected to be suitable in the macroscale synthesis of carboxylic acids using isotopically unmodified carbon monoxide. Radical carbonylation was applied to improve the synthesis of an extensively used PET tracer, [carbonyl-11C]WAY-100635. The tracer was synthesized in one step, whereas a common approach via Grignard reagents requires three steps. In addition, several (13C)compounds were synthesised using the described methods. Free radical carbonylation may be used for the 11C-carbonylation of alkyl iodides, whereas transition-metal carbonylation – of aryl halides and triflates. Thus, the two carbonylation methods are complementary with respect to the scope of synthetic targets.

In this thesis, we included results from two studies. The first one considered the effects of the blood volume changes, during blood donation, on the heart rate variability (HRV) measured, non-invasively, form electrocardiographic (ECG) and photoplethysmographic (PPG) signals. Our results showed that, during blood donation, there were no significant changes in the pulsatile area of PPG signal, while heart rate increased. No significant changes were noticed in HRV extracted from both signals. Error analysis between the HRV extracted from ECG and peak interval variability (PIV) suggested that the error during blood donation was increased which means that the use of PIV extracted from PPG signal, used as a replacement diagnostic tool in clinical applications, needs further investigations and should be carefully studied in non-stationary cardiovascular situations such as blood donation. The imbalance between the two branches of the autonomic nervous system, sympathetic and parasympathetic, vagal, may result in a harmful activation of myocardial tissues which cause arrhythmias and sudden cardiac death. Although the study of the sympathovagal balance have been attracting many researchers, further studies are needed to elucidate the effects of many kinds of drugs on the autonomic modulation of the cardiac muscle, specifically, the cells of sinoatrial (SA) node. The aim of the second part of this thesis was to assess the effects of calcium channel blocker (Verapamil), calcium channel sensitizer (Levosimendan), calcium chloride (CaCl2), the combinations of verapamil/ CaCl2, levosimendan/ CaCl2, and noradrenaline infusion on beat-to-beat cardiovascular variability represented, in this research, by systolic blood pressure variability (SBPV), and stroke volume variability (SVV) signals. We used Fat Fourier Transform (FFT) to evaluate the power spectral density of the fluctuations in both signals to evaluate the effects of short-term treatments with those drugs on the sympathovagal balance in normal rats. Then, we compared the spectra obtained from SBPV and SVV to decide which of these fluctuations along with corresponding spectrum was more able to provide a clear feedback about the autonomic nervous system. Our data suggests that there were a significant correlations between low- (LF), mid- (MF), and high-frequency (HF) spectra obtained from SBPV and SVV except between the HF spectra estimated from after the infusion of levosimendan where a poor correlation (r = 0.530, p = 0.281) was noticed. This that both HF components obtained provide different information regarding the autonomic nervous system modulation of the SA node cells, while the results obtained from the rest of experiments showed that both signals provide same information about the modulation of sympathetic and parasympathetic tone due to all stages of different drugs infusion studied in this thesis. Besides that, we found that both spectra may be used to track the fluctuations in the cardiac output as a result of the drugs infusion.

Increasing globalization and transnational trends in business have resulted in greater contact with people from different cultures. However, in any cross-cultural encounter, miscommunication and misunderstandings are likely to occur. In a workplace setting, these can seriously undermine job performance and employee relations. The Intercultural Sensitizer is a cross-cultural training tool that is designed to increase the likelihood that trained individuals will make accurate interpretations concerning behavior observed in individuals from other cultural groups (Albert, 1983) . The purpose of this study was two-fold: (1) to identify cultural differences between Americans and Japanese that can lead to misunderstandings in the workplace and hinder communication, and (2) to construct an intercultural sensitizer that will enable the two cultural groups to interact more effectively with each other. The study's five-phase research design was based on Albert's (1983) delineation of the construction of an intercultural sensitizer. Twenty-four episodes were constructed and statistically analyzed to determine if there was a difference in the way the two cultural groups responded to a given situation. Nine episodes yielded critical values significant at the .05 level. The study concluded that there while there are differences in the cultural perspectives of American and Japanese business professionals, the two groups also share common cultural assumptions. The study's findings have numerous implications for cross-cultural corporate training and higher education.

Les réactions allergiques telles que les réactions d’hypersensibilité de contact (HSC) sont un problème de santé publique. Il s’agit d’une réaction inflammatoire aiguë qui survient suite à des expositions répétées d’une molécule allergisante avec la peau et dans laquelle les cellules dendritiques (DC) jouent un rôle essentiel. Les composés chimiques tels que le dinitrochlorobenzène (DNCB) ou le cinnamaldéhyde (CinA), responsables d'HSC, sont capables d’induire un stress chimique et de produire des espèces réactives de l’oxygène (ERO). Parmi les voies de détoxication en réponse aux xénobiotiques, la voie Nrf2/Keap1 est une voie centrale connue pour la détection de composés électrophiles. A l’état basal et en absence de stress, Nrf2 est couplé à son répresseur cytosolique Keap1 qui assure sa dégradation via le protéasome. En présence d’un stress chimique, Nrf2 transloque dans le noyau et induit l’expression des gènes antioxydants [hème-oxygénase 1 (ho-1), NADPH quinone oxydoréductase (nqo1), glutathione-s-transférase (gst)]. En absence de Nrf2, nous avons montré que le DNCB et le CinA induisent la mort cellulaire des DC via l'activation des caspases impliquées dans la voie mitochondriale ou intrinsèque de l'apoptose. Cette mort cellulaire induite par le DNCB est ERO dépendante tandis que celle induite par le CinA est moins sensible à la production des ERO. En présence de Nrf2, la survie des DC est régulée par l'expression de bcl-2, un gène antiapoptotique, et des gènes antioxydants. Nrf2 semblerait activer ou réprimer la transcription des gènes et ce en fonction de la molécule testée, du temps de traitement. Par ailleurs, nous avons également montré que Nrf2 joue un rôle clef dans les phases de sensibilisation et d'élicitation de la réaction d'HSC mais également au cours de l'irritation. Des transferts adoptifs de DC ont permis de montrer le rôle clef de Nrf2 dans la DC au cours de l'HSC. Enfin, notre étude montre que Nrf2 régule les Treg au niveau du tissu cutané et participe à la tolérance cutanée. / Allergic reactions such as contact hypersensitivity (CHS) are a problem of public health occurring after repeated exposures to contact sensitizers. CHS is a common skin disease involving dendritic cells (DC) playing a key role in this pathology. Contact sensitizers, like dinitrochlorobenzene (DNCB) or cinnamaldehyde (CinA) are known to induce reactive oxygen species (ROS) production. The Nrf2/Keap1 pathway is central for detoxification. In the absence of a chemical stress, Keap1 associates with Nrf2 and leading to its degradation. In the presence of an electrophilic compound like contact sensitizers, Keap1’s conformation is modified leading to Nrf2 translocation to the nucleus and transcription of its target genes [heme-oxygénase 1 (ho-1), NADPH quinone oxydoreductase (nqo1), glutathione-s-transferase (gst)]. We showed, for the first time, that Nrf2 controls the loss of mitochondrial membrane potential and caspase-3/7 activity in DC activated by contact sensitizers. In the absence of Nrf2, DNCB and CinA induced DC apoptosis via caspase activation involved in intrinsic pathway of apoptosis also called ‘mitochondrial pathway’. This apoptosis was mainly mediated by the production of ROS in response to DNCB. However, ROS faintly control CinA-induced cell death. We also showed that Nrf2 controls the transcription of the anti-apoptotic gene bcl-2 in response to DNCB or CinA and also the transcription of immune related and antioxidant genes that could be implicated in DC apoptosis.Otherwise, we also showed that Nrf2 plays a key role in sensitization and elicitation phases of CHS and even in the irritation phase. Adoptive transfer experiments showed that Nrf2 plays a crucial role in DC during CHS.Finally, we showed that Nrf2 regulates skin Treg and participates to skin tolerance.

L’eczéma allergique de contact (EAC) est une réaction inflammatoire aiguë médiée par les lymphocytes T (LT), survenant suite à l’exposition répétée de la peau avec une molécule allergisante présente dans l’environnement quotidien ou professionnel. Les molécules allergisantes sont des composés de faible poids moléculaire, appelés haptènes, qui activent les cellules dendritiques (DC). Les DC jouent un rôle essentiel dans la mise en place d’un EAC : elles acquièrent un phénotype mature, contrôlé par la voie des MAPK et la voie NF-B, leur permettant de présenter l’haptène aux LT afin d’initier ainsi une réponse immunitaire spécifique.Nous avons identifié au sein de la DC une nouvelle kinase, la protéine kinase CK2, indispensable à l’acquisition d’un phénotype mature et à la sécrétion de cytokines pro-inflammatoires clés dans l’orientation d’une réponse immunitaire. L’activité de la CK2 dans la DC est nécessaire à la génération d’une réponse Th1 en contrôlant la sécrétion d’IFN par les LT, et maintient une réponse Th17 préexistante. De plus, la CK2 permet à la DC de contrôler l’induction d’une réponse Th2 spontanée. Par ailleurs, la CK2 contrôle l’expression des gènes cibles de Nrf2, un facteur de transcription majeur dans la lutte contre le stress chimique induit par les haptènes. L’activation de Nrf2 met en jeu de nombreuses voies de signalisation, et nous avons mis en évidence c-Jun, facteur de transcription activé par les molécules allergisantes, comme un potentiel partenaire transcriptionnel de Nrf2. / Allergic contact dermatitis represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated inflammatory skin disease caused by chemicals present in daily or professional environment. Contact sensitizers are low molecular weight compounds termed haptens. These molecules are known to induce an up-regulation of phenotypic markers and cytokine secretion in dendritic cells (DCs), professional antigen-presenting cells, leading to the generation of effector T lymphocytes (LT).We identified a new kinase, termed CK2 (formerly casein kinase 2), as a key kinase in DCs in the acquisition of a mature phenotype and in the production of pro-inflammatory cytokines, involved in T cell polarization in response to contact sensitizers. CK2 activity in DC is necessary to induce a Th1 polarization by controlling the secretion of IFN- by LT, and maintains a pre-existing Th17 response. Moreover, CK2 in DC negatively controls a spontaneous Th2 response.Finally, CK2 controls the expression of Nrf2 target genes mRNA. Nrf2 is a protective transcription factor playing a major role in detoxification, oxidative stress and allergic inflammation generated by contact sensitizers. Nrf2 activation involves different kinases and we highlight that c-Jun could be bound to Nrf2 to generate an active transcriptional complex in response to chemicals.