A Comparative Review of Computational Methods as Applied to Gold(I) Complexes and Mechanisms

In the last two decades, the field of homogeneous gold catalysis has been

extremely active, growing at a rapid pace. Another rapidly-growing field—that of

computational chemistry—has often been applied to the investigation of various gold-

catalyzed reaction mechanisms. Unfortunately, a number of recent mechanistic studies

have utilized computational methods that have been shown to be inappropriate and

inaccurate in their description of gold chemistry. This work presents an overview of

available computational methods with a focus on the approximations and limitations

inherent in each, and offers a review of experimentally-characterized gold(I) complexes

and proposed mechanisms as compared with their computationally-modeled

counterparts. No aim is made to identify a “recommended” computational method for

investigations of gold catalysis; rather, discrepancies between experimentally and

computationally obtained values are highlighted, and the systematic errors between

different computational methods are discussed.

Factors and mechanisms controlling soil organic carbon turnover in subsoils of agricultural sites

Two-third of the terrestrial C is stored in soils, and more than 50% of soil organic C (SOC) is stored in subsoils from 30 – 100 cm. Hence, subsoil is important as a source or sink for CO2 in the global carbon cycle. Especially the stable organic carbon (OC) is stored in subsoil, as several studies have shown that subsoil OC is of a higher average age than topsoil OC. However, there is still a lack of knowledge regarding the mechanisms of C sequestration and C turnover in subsoil. Three main factors are discussed, which possibly reduce carbon turnover rates in subsoil: Resource limitation, changes in the microbial community, and changes in gas conditions. The experiments conducted in this study, which aimed to elucidate the importance of the mentioned factors, focused on two neighbouring arable sites, with depth profiles differing in SOC stocks: One Colluvic Cambisol (Cam) with high SOC contents (8-12 g kg-1) throughout the profile and one Haplic Luvisol (Luv) with low SOC contents (3-4 g kg-1) below 30 cm depth. The first experiment was designed to gain more knowledge regarding the microbial community and its influence on carbon sequestration in subsoil. Soil samples were taken at four different depths on the two sites. Microbial biomass C (MBC) was determined to identify depth gradients in relation to the natural C availability. Bacterial and fungal residues as well as ergosterol were determined to quantify changes in the in the microbial community composition. Multi-substrate-induced-respiration (MSIR) was used to identify shifts in functional diversity of the microbial community. The MSIR revealed that substrate use in subsoil differed significantly from that in topsoil and also differed highly between the two subsoils, indicating a strong influence of resource limitations on microbial substrate use. Amino sugar analysis and the ratio of ergosterol to microbial biomass C showed that fungal dominance decreased with depth. The results clearly demonstrated that microbial parameters changed with depth according to substrate availability. The second experiment was an incubation experiment using subsoil gas conditions with and without the addition of C4 plant residues. Soil samples were taken from topsoil and subsoil of the two sites. SOC losses during the incubation, were not influenced by the subsoil gas conditions. Plant-derived C losses were generally stronger in the Cam (7.5 mg g-1), especially at subsoil gas conditions, than in the Luv (7.0 mg g-1). Subsoil gas conditions had no general effects on microbial measures with and without plant residue addition. However, the contribution of plant-derived MBC to total MBC was significantly reduced at subsoil gas conditions. This lead to the conclusion that subsoil gas conditions alter the metabolism of microorganisms but not the degradation of added plant residues is general. The third experiment was a field experiment carried out for two years. Mesh bags containing original soil material and maize root residues (C4 plant) were buried at three different depths at the two sites. The recovery of the soilbags took place 12, 18, and 24 months after burial. We determined the effects of these treatments on SOC, density fractions, and MBC. The mean residence time for maize-derived C was similar at all depths and both sites (403 d). MBC increased to a similar extent (2.5 fold) from the initial value to maximum value. This increase relied largely on the added maize root residues. However, there were clear differences visible in terms of the substrate use efficiency, which decreased with depth and was lower in the Luv than in the Cam. Hence freshly added plant material is highly accessible to microorganisms in subsoil and therefore equally degraded at both sites and depths, but its metabolic use was determined by the legacy of soil properties. These findings provide strong evidence that resource availability from autochthonous SOM as well as from added plant residues have a strong influence on the microbial community and its use of different substrates. However, under all of the applied conditions there was no evidence that complex substrates, i.e. plant residues, were less degraded in subsoil than in topsoil.

Transition metal complexes of some N4-phenylsemicarbazones: crystal structures and spectral studies

The work embodied in this thesis was carried out by the author in the Department of Applied Chemistry, CUSAT, Kochi, during the period 2009-2012. The thesis is an introduction to our attempts to evaluate the coordination behavior of some compounds of our interest. The biological activities of semicarbazones and their metal complexes have been an active area of research during the past years because of their significant role in naturally occurring biological systems. Tridentate NNO and ONO semicarbazone systems formed from heterocyclic and aromatic carbonyl compounds and their transition metal complexes are wellauthenticated compounds in this field and their synthesis, crystal structures and spectral studies are well desirable. Hence, we decided to develop a research program aimed at the syntheses, crystal structures and spectral studies of new N4- phenylsemicarbazones derived from 2-formylpyridine and 3-ethoxysalicylaldehyde and their transition metal complexes and new transition metal complexes of 2- benzoylpyridine-N4-phenylsemicarbazone. In addition to various physicochemical methods of analysis, single crystal X-ray diffraction studies were also used for the characterization of the complexes.

Proficiency and mechanisms of perturbation of mature T-cell homeostasis by the TCL1 family of oncogenes

In the first part of this thesis, the oncogenic potential of TCL1A family genes was comparatively evaluated by using gamma-retroviral vectors to introduce human TCL1A, MTCP1, and TML1 into hematopoietic stem cells/hematopoietic progenitor cells (HSC/HPC) of wild type mice that were transplanted into wild type recipients. TCL1A and MTCP1 recipient mice predominantly developed B-cell malignancies after a median survival of 388 days and 394 days, respectively. The presented data indicates that TCL1A and MTCP1 are oncogenes with comparable oncogenic potential and shows for the first time that MTCP1 is not only a T-cell oncogene, but is able to transform B cells as well. The third family member TML1 induced the development of immature T-cell malignancies in only a few mice. This study provides first evidence for its oncogenic function. Additionally, the transforming potential of compartment-targeted TCL1A variants was evaluated by retroviral expression of a membrane localizing myristoylated (myr-TCL1A) and a nuclear localizing (nls-TCL1A) variant. Recipients of HSC/HPC transduced with myr-TCL1A and nls-TCL1A predominantly developed B-cell malignancies after a median survival of 360 days and 349 days, respectively. There was a significantly shorter latency period for nls-TCL1A compared to the previously described generic TCL1A. Gene expression analysis revealed higher similarities between expression profiles of tumors induced by TCL1A and nls-TCL1A. Together these data implicate that TCL1A’s predominant oncogenic function might rely on its nuclear presence. The second part of this thesis aims to understand if and how TCR stimulation affects the transforming potential of TCL1A. Mature OT-1 T cells carrying monoclonal TCR’s that specifically recognize ovalbumin (OVA) were retrovirally transduced with TCL1A and repeatedly stimulated in vivo with OVA-peptides. TCR stimulated recipient mice of TCL1A transduced T cells showed a significantly accelerated leukemic outgrowth and a reduced median survival of 305 days, when compared to unstimulated recipients (417 days). These data strongly implicate a pro-leukemogenic cooperation of TCL1A and TCR signals that might be actionable in upcoming interventional designs.

Lobbying in a transatlantic comparison: opportunity structures and lobbying content in the US and the EU

Despite vast literatures on interest representation in the United States (US) and the European Union (EU), few studies have tried to compare lobbying across the two cases. Those who do are interested primarily in the existence of different lobbying styles and distinguish between an aggressive pressure group approach in the US and a more consensus oriented informational lobbying in the EU. However, the origins of these differences have received little attention and references most often point to different political “cultures” and lobbying traditions. This paper takes issue with this cultural explanation and links the observed lobbying styles with differences in the design of the political institutions that private actors have to interact with. It argues that divided policy authority in the US allows for interest group bargaining while shared policy competencies in the EU constrain not only policy-makers but also lobbyists to adopt a more consensus-oriented approach. The effect of political institutions on the form of lobbying, in turn, can have important implications for the comparison of different policy areas across countries, because the policy stances of private actors cannot always be assumed to be exogenous to the policy process in which they are active.

Ocean acidification in the subpolar North Atlantic: rates and mechanisms controlling pH changes

Repeated hydrographic sections provide critically needed data on and understanding of changes in basin-wide ocean CO2 chemistry over multi-decadal timescales. Here, high-quality measurements collected at twelve cruises carried out along the same track between 1991 and 2015 have been used to determine long-term changes in ocean CO2 chemistry and ocean acidification in the Irminger and Iceland basins of the North Atlantic Ocean. Trends were determined for each of the main water masses present and are discussed in the context of the basin-wide circulation. The pH has decreased in all water masses of the Irminger and Iceland basins over the past 25 years with the greatest changes in surface and intermediate waters (between −0.0010 ± 0.0001 and −0.0018 ± 0.0001 pH units yr−1). In order to disentangle the drivers of the pH changes, we decomposed the trends into their principal drivers: changes in temperature, salinity, total alkalinity (AT) and total dissolved inorganic carbon (both its natural and anthropogenic components). The increase in anthropogenic CO2 (Cant) was identified as the main agent of the pH decline, partially offset by AT increases. The acidification of intermediate waters caused by Cant uptake has been reinforced by the aging of the water masses over the period of our analysis. The pH decrease of the deep overflow waters in the Irminger basin was similar to that observed in the upper ocean and was mainly linked to the Cant increase, thus reflecting the recent contact of these deep waters with the atmosphere.

Thiolated Au18cluster: preferred Ag sites for doping, structures, and optical and chiroptical properties

Recently, the X-ray determined structure of the thiolated Au18 cluster has been reported. In this communication, we addressed a study of structures and chiroptical properties of thiolated Au18 cluster doped with up to ten Ag atoms, which have been calculated by Time Dependent Density Functional Theory (TD-DFT). The number of Ag atoms was steadily varied and more stable isomers showed optical and Circular Dichroism (CD) spectra distinct from that found for the parent Au18 cluster. Doping with more than four Ag atoms results in enhancement of the oscillator strength of the HOMO–LUMO peak and it is expected that this feature can be exploited for photoluminescence applications.

The J1030 field: a new window on early large scale structures and faint radio-galaxy populations

The correlations between the evolution of the Super Massive Black Holes (SMBHs) and their host galaxies suggests that the SMBH accretion on sub-pc scales (active galactice nuclei, AGN) is linked to the building of the galaxy over kpc scales, through the so called AGN feedback. Most of the galaxy assembly occurs in overdense large scale structures (LSSs). AGN residing in powerful sources in LSSs, such as the proto-brightest cluster galaxies (BCGs), can affect the evolution of the surrounding intra-cluster medium (ICM) and nearby galaxies. Among distant AGN, high-redshift radio-galaxies (HzRGs) are found to be excellent BCG progenitor candidates. In this Thesis we analyze novel interferometric observations of the so-called "J1030" field centered around the z = 6.3 SDSS Quasar J1030+0524, carried out with the Atacama large (sub-)millimetre array (ALMA) and the Jansky very large array (JVLA). This field host a LSS assembling around a powerful HzRG at z = 1.7 that shows evidence of positive AGN feedback in heating the surrounding ICM and promoting star-formation in multiple galaxies at hundreds kpc distances. We report the detection of gas-rich members of the LSS, including the HzRG. We showed that the LSS is going to evolve into a local massive cluster and the HzRG is the proto-BCG. we unveiled signatures of the proto-BCG's interaction with the surrounding ICM, strengthening the positive AGN feedback scenario. From the JVLA observations of the "J1030" we extracted one of the deepest extra-galactic radio surveys to date (~12.5 uJy at 5 sigma). Exploiting the synergy with the X-ray deep survey (~500 ks) we investigated the relation of the X-ray/radio emission of a X-ray-selected sample, unveiling that the radio emission is powered by different processes (star-formation and AGN), and that AGN-driven sample is mostly composed by radio-quiet objects that display a significant X-ray/radio correlation.

Sacred Music, Sacred Journeys : What Makes an Event Postcolonial?

Fanon, Senghor, and Ela took a radical stance in criticising the structures and mechanisms of power in hegemonic situations and relations between colonial subjects and colonial masters. They aimed to liberate African societies by decolonising the mind, culture and religion of colonial subjects. In this respect, we are concerned with the continuities and ruptures of the colonial encounter and its unequal relationships. Switzerland does not have an official colonial history and yet, Swiss companies and migrants were and are part of the world's colonies. In our contribution, we question what makes an event postcolonial : in other words, how are postcolonial relations negotiated in Switzerland? We discuss this question by analysing two annual sacred journeys in Switzerland that have been invented for and by African Christians (clerics and laity) together with the leaders of the Swiss Catholic church : one to the relics of African saints in St. Maurice, canton Valais and the other to the Black Madonna, the Virgin Mary of Einsiedeln, in the canton Schwyz. These events are empowered by the performance of African choirs - their music, dance, and costumes - but to which end and in which way?

Learning of shared attention in sociable robotics

Sociable robots are embodied agents that are part of a heterogeneous society of robots and humans. They Should be able to recognize human beings and each other, and to engage in social, interactions. The use of a robotic architecture may strongly reduce the time and effort required to construct a sociable robot. Such architecture must have structures and mechanisms to allow social interaction. behavior control and learning from environment. Learning processes described oil Science of Behavior Analysis may lead to the development of promising methods and Structures for constructing robots able to behave socially and learn through interactions from the environment by a process of contingency learning. In this paper, we present a robotic architecture inspired from Behavior Analysis. Methods and structures of the proposed architecture, including a hybrid knowledge representation. are presented and discussed. The architecture has been evaluated in the context of a nontrivial real problem: the learning of the shared attention, employing an interactive robotic head. The learning capabilities of this architecture have been analyzed by observing the robot interacting with the human and the environment. The obtained results show that the robotic architecture is able to produce appropriate behavior and to learn from social interaction. (C) 2009 Elsevier Inc. All rights reserved.

Estudo da relação estrutura/atividade para as ações neurotóxica/neuroprotetora das acilpoliaminotoxinas NSTX-3 e JSTX-3 em sistema nervoso central de ratos

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Insights on the structure of native CNF, an endogenous phospholipase A(2) inhibitor from Crotalus durissus terrificus, the South American rattlesnake

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Covalent protein adduction by drugs of abuse

Recreational abuse of the drugs cocaine, methamphetamine, and morphine continues to be prevalent in the United States of America and around the world. While numerous methods of detection exist for each drug, they are generally limited by the lifetime of the parent drug and its metabolites in the body. However, the covalent modification of endogenous proteins by these drugs of abuse may act as biomarkers of exposure and allow for extension of detection windows for these drugs beyond the lifetime of parent molecules or metabolites in the free fraction. Additionally, existence of covalently bound molecules arising from drug ingestion can offer insight into downstream toxicities associated with each of these drugs. This research investigated the metabolism of cocaine, methamphetamine, and morphine in common in vitro assay systems, specifically focusing on the generation of reactive intermediates and metabolites that have the potential to form covalent protein adducts. Results demonstrated the formation of covalent adduction products between biological cysteine thiols and reactive moieties on cocaine and morphine metabolites. Rigorous mass spectrometric analysis in conjunction with in vitro metabolic activation, pharmacogenetic reaction phenotyping, and computational modeling were utilized to characterize structures and mechanisms of formation for each resultant thiol adduction product. For cocaine, data collected demonstrated the formation of adduction products from a reactive arene epoxide intermediate, designating a novel metabolic pathway for cocaine. In the case of morphine, data expanded on known adduct-forming pathways using sensitive and selective analysis techniques, following the known reactive metabolite, morphinone, and a proposed novel metabolite, morphine quinone methide. Data collected in this study describe novel metabolic events for multiple important drugs of abuse, culminating in detection methods and mechanistic descriptors useful to both medical and forensic investigators when examining the toxicology associated with cocaine, methamphetamine, and morphine.

Covalent Protein Adduction by Drugs of Abuse

Recreational abuse of the drugs cocaine, methamphetamine, and morphine continues to be prevalent in the United States of America and around the world. While numerous methods of detection exist for each drug, they are generally limited by the lifetime of the parent drug and its metabolites in the body. However, the covalent modification of endogenous proteins by these drugs of abuse may act as biomarkers of exposure and allow for extension of detection windows for these drugs beyond the lifetime of parent molecules or metabolites in the free fraction. Additionally, existence of covalently bound molecules arising from drug ingestion can offer insight into downstream toxicities associated with each of these drugs. This research investigated the metabolism of cocaine, methamphetamine, and morphine in common in vitro assay systems, specifically focusing on the generation of reactive intermediates and metabolites that have the potential to form covalent protein adducts. Results demonstrated the formation of covalent adduction products between biological cysteine thiols and reactive moieties on cocaine and morphine metabolites. Rigorous mass spectrometric analysis in conjunction with in vitro metabolic activation, pharmacogenetic reaction phenotyping, and computational modeling were utilized to characterize structures and mechanisms of formation for each resultant thiol adduction product. For cocaine, data collected demonstrated the formation of adduction products from a reactive arene epoxide intermediate, designating a novel metabolic pathway for cocaine. In the case of morphine, data expanded on known adduct-forming pathways using sensitive and selective analysis techniques, following the known reactive metabolite, morphinone, and a proposed novel metabolite, morphine quinone methide. Data collected in this study describe novel metabolic events for multiple important drugs of abuse, culminating in detection methods and mechanistic descriptors useful to both medical and forensic investigators when examining the toxicology associated with cocaine, methamphetamine, and morphine.