Baryon and lepton numbers in particle physics beyond the standard model

The works presented in this thesis explore a variety of extensions of the standard model of particle physics which are motivated by baryon number (B) and lepton number (L), or some combination thereof. In the standard model, both baryon number and lepton number are accidental global symmetries violated only by non-perturbative weak effects, though the combination B-L is exactly conserved. Although there is currently no evidence for considering these symmetries as fundamental, there are strong phenomenological bounds restricting the existence of new physics violating B or L. In particular, there are strict limits on the lifetime of the proton whose decay would violate baryon number by one unit and lepton number by an odd number of units.

The first paper included in this thesis explores some of the simplest possible extensions of the standard model in which baryon number is violated, but the proton does not decay as a result. The second paper extends this analysis to explore models in which baryon number is conserved, but lepton flavor violation is present. Special attention is given to the processes of μ to e conversion and μ → eγ which are bound by existing experimental limits and relevant to future experiments.

The final two papers explore extensions of the minimal supersymmetric standard model (MSSM) in which both baryon number and lepton number, or the combination B-L, are elevated to the status of being spontaneously broken local symmetries. These models have a rich phenomenology including new collider signatures, stable dark matter candidates, and alternatives to the discrete R-parity symmetry usually built into the MSSM in order to protect against baryon and lepton number violating processes.

Development and Application of Embedding Methods for the Simulation of Large Chemical Systems

The high computational cost of correlated wavefunction theory (WFT) calculations has motivated the development of numerous methods to partition the description of large chemical systems into smaller subsystem calculations. For example, WFT-in-DFT embedding methods facilitate the partitioning of a system into two subsystems: a subsystem A that is treated using an accurate WFT method, and a subsystem B that is treated using a more efficient Kohn-Sham density functional theory (KS-DFT) method. Representation of the interactions between subsystems is non-trivial, and often requires the use of approximate kinetic energy functionals or computationally challenging optimized effective potential calculations; however, it has recently been shown that these challenges can be eliminated through the use of a projection operator. This dissertation describes the development and application of embedding methods that enable accurate and efficient calculation of the properties of large chemical systems.

Chapter 1 introduces a method for efficiently performing projection-based WFT-in-DFT embedding calculations on large systems. This is accomplished by using a truncated basis set representation of the subsystem A wavefunction. We show that naive truncation of the basis set associated with subsystem A can lead to large numerical artifacts, and present an approach for systematically controlling these artifacts.

Chapter 2 describes the application of the projection-based embedding method to investigate the oxidative stability of lithium-ion batteries. We study the oxidation potentials of mixtures of ethylene carbonate (EC) and dimethyl carbonate (DMC) by using the projection-based embedding method to calculate the vertical ionization energy (IE) of individual molecules at the CCSD(T) level of theory, while explicitly accounting for the solvent using DFT. Interestingly, we reveal that large contributions to the solvation properties of DMC originate from quadrupolar interactions, resulting in a much larger solvent reorganization energy than that predicted using simple dielectric continuum models. Demonstration that the solvation properties of EC and DMC are governed by fundamentally different intermolecular interactions provides insight into key aspects of lithium-ion batteries, with relevance to electrolyte decomposition processes, solid-electrolyte interphase formation, and the local solvation environment of lithium cations.

Investigations of DNA-mediated protein oxidation

DNA charge transport (CT) involves the efficient transfer of electrons or electron holes through the DNA π-stack over long molecular distances of at least 100 base-pairs. Despite this shallow distance dependence, DNA CT is sensitive to mismatches or lesions that disrupt π-stacking and is critically dependent on proper electronic coupling of the donor and acceptor moieties into the base stack. Favorable DNA CT is very rapid, occurring on the picosecond timescale. Because of this speed, electron holes equilibrate along the DNA π-stack, forming a characteristic pattern of DNA damage at low oxidation potential guanine multiplets. Furthermore, DNA CT may be used in a biological context. DNA processing enzymes with 4Fe4S clusters can perform DNA-mediated electron transfer (ET) self-exchange reactions with other 4Fe4S cluster proteins, even if the proteins are quite dissimilar, as long as the DNA-bound [4Fe4S]^3+/2+ redox potentials are conserved. This mechanism would allow low copy number DNA repair proteins to find their lesions efficiently within the cell. DNA CT may also be used biologically for the long-range, selective activation of redox-active transcription factors. Within this work, we pursue other proteins that may utilize DNA CT within the cell and further elucidate aspects of the DNA-mediated ET self-exchange reaction of 4Fe4S cluster proteins.

Dps proteins, bacterial mini-ferritins that protect DNA from oxidative stress, are implicated in the survival and virulence of pathogenic bacteria. One aspect of their protection involves ferroxidase activity, whereby ferrous iron is bound and oxidized selectively by hydrogen peroxide, thereby preventing formation of damaging hydroxyl radicals via Fenton chemistry. Understanding the specific mechanism by which Dps proteins protect the bacterial genome could inform the development of new antibiotics. We investigate whether DNA-binding E. coli Dps can utilize DNA CT to protect the genome from a distance. An intercalating ruthenium photooxidant was employed to generate oxidative DNA damage via the flash-quench technique, which localizes to a low potential guanine triplet. We find that Dps loaded with ferrous iron, in contrast to Apo-Dps and ferric iron-loaded Dps which lack available reducing equivalents, significantly attenuates the yield of oxidative DNA damage at the guanine triplet. These data demonstrate that ferrous iron-loaded Dps is selectively oxidized to fill guanine radical holes, thereby restoring the integrity of the DNA. Luminescence studies indicate no direct interaction between the ruthenium photooxidant and Dps, supporting the DNA-mediated oxidation of ferrous iron-loaded Dps. Thus DNA CT may be a mechanism by which Dps efficiently protects the genome of pathogenic bacteria from a distance.

Further work focused on spectroscopic characterization of the DNA-mediated oxidation of ferrous iron-loaded Dps. X-band EPR was used to monitor the oxidation of DNA-bound Dps after DNA photooxidation via the flash-quench technique. Upon irradiation with poly(dGdC)₂, a signal arises with g = 4.3, consistent with the formation of mononuclear high-spin Fe(III) sites of low symmetry, the expected oxidation product of Dps with one iron bound at each ferroxidase site. When poly(dGdC)₂ is substituted with poly(dAdT)₂, the yield of Dps oxidation is decreased significantly, indicating that guanine radicals facilitate Dps oxidation. The more favorable oxidation of Dps by guanine radicals supports the feasibility of a long-distance protection mechanism via DNA CT where Dps is oxidized to fill guanine radical holes in the bacterial genome produced by reactive oxygen species.

We have also explored possible electron transfer intermediates in the DNA-mediated oxidation of ferrous iron-loaded Dps. Dps proteins contain a conserved tryptophan residue in close proximity to the ferroxidase site (W52 in E. coli Dps). In comparison to WT Dps, in EPR studies of the oxidation of ferrous iron-loaded Dps following DNA photooxidation, W52Y and W52A mutants were deficient in forming the characteristic EPR signal at g = 4.3, with a larger deficiency for W52A compared to W52Y. In addition to EPR, we also probed the role of W52 Dps in cells using a hydrogen peroxide survival assay. Bacteria containing W52Y Dps survived the hydrogen peroxide challenge more similarly to those containing WT Dps, whereas cells with W52A Dps died off as quickly as cells without Dps. Overall, these results suggest the possibility of W52 as a CT hopping intermediate.

DNA-modified electrodes have become an essential tool for the study of the redox chemistry of DNA processing enzymes with 4Fe4S clusters. In many cases, it is necessary to investigate different complex samples and substrates in parallel in order to elucidate this chemistry. Therefore, we optimized and characterized a multiplexed electrochemical platform with the 4Fe4S cluster base excision repair glycosylase Endonuclease III (EndoIII). Closely packed DNA films, where the protein has limited surface accessibility, produce EndoIII electrochemical signals sensitive to an intervening mismatch, indicating a DNA-mediated process. Multiplexed analysis allowed more robust characterization of the CT-deficient Y82A EndoIII mutant, as well as comparison of a new family of mutations altering the electrostatics surrounding the 4Fe4S cluster in an effort to shift the reduction potential of the cluster. While little change in the DNA-bound midpoint potential was found for this family of mutants, likely indicating the dominant effect of DNA-binding on establishing the protein redox potential, significant variations in the efficiency of DNA-mediated electron transfer were apparent. On the basis of the stability of these proteins, examined by circular dichroism, we proposed that the electron transfer pathway in EndoIII can be perturbed not only by the removal of aromatic residues but also through changes in solvation near the cluster.

While the 4Fe4S cluster of EndoIII is relatively insensitive to oxidation and reduction in solution, we have found that upon DNA binding, the reduction potential of the [4Fe4S]^3+/2+ couple shifts negatively by approximately 200 mV, bringing this couple into a physiologically relevant range. Demonstrated using electrochemistry experiments in the presence and absence of DNA, these studies do not provide direct molecular evidence for the species being observed. Sulfur K-edge X-ray absorbance spectroscopy (XAS) can be used to probe directly the covalency of iron-sulfur clusters, which is correlated to their reduction potential. We have shown that the Fe-S covalency of the 4Fe4S cluster of EndoIII increases upon DNA binding, stabilizing the oxidized [4Fe4S]³⁺ cluster, consistent with a negative shift in reduction potential. The 7% increase in Fe-S covalency corresponds to an approximately 150 mV shift, remarkably similar to DNA electrochemistry results. Therefore we have obtained direct molecular evidence for the shift in 4Fe4S reduction potential of EndoIII upon DNA binding, supporting the feasibility of our model whereby these proteins can utilize DNA CT to cooperate in order to efficiently find DNA lesions inside cells.

In conclusion, in this work we have explored the biological applications of DNA CT. We discovered that the DNA-binding bacterial ferritin Dps can protect the bacterial genome from a distance via DNA CT, perhaps contributing to pathogen survival and virulence. Furthermore, we optimized a multiplexed electrochemical platform for the study of the redox chemistry of DNA-bound 4Fe4S cluster proteins. Finally, we have used sulfur K-edge XAS to obtain direct molecular evidence for the negative shift in 4Fe4S cluster reduction potential of EndoIII upon DNA binding. These studies contribute to the understanding of DNA-mediated protein oxidation within cells.

Computation of the ambiguity function for circularly symmetric pupils

A method of computing the ambiguity function (AF) for a circularly symmetric pupil function is presented. The AFs of a clear aperture and two shaded apertures are considered in detail and an explicit expression for the first of these AFs is given. We explain these results in the context of the well-known optical transfer function theory and show a primary application of these computations. A good analytic approximation is also introduced, providing an alternative method for calculating the AF, in a simpler way.

Moral e disciplina: monges e escravos no espaço monástico beneditino na Corte Imperial

Esta pesquisa trata das alterações ocorridas na propriedade dos monges da Ordem de São Bento no Rio de Janeiro. O crescimento da cidade, a falta de monges nos claustros e o aumento do número de escravos no século XIX, contribuíram para a configuração desse espaço e também nas mudanças dos preceitos religiosos. Com base a Regra de São Bento novas práticas foram apontadas nesse universo monástico exigindo maior rigor na conduta dos monges e da sua mão-de-obra cativa no cotidiano do mosteiro. Dessa forma, aponto como as transformações ocorridas na administração da Congregação Beneditina do Brasil e os interesses do Governo Imperial no patrimônio da Ordem estabeleceram uma relação de poder entre os monges e seus escravos, no período de 1819 a 1842. A partir da análise da Confraria do Rosário, constituída na capela-mor do mosteiro, ilumino o lugar dos cativos nessa nova organização, observando-a como parte de uma tática de produção de corpos submissos à moral e à disciplina.

Studies of dinucleoside monophosphates and monomer-polynucleotide interactions by proton magnetic resonance

The nature of the intra- and intermolecular base-stacking interactions involving several dinucleoside monophosphates in aqueous solution have been investigated by proton magnetic resonance spectrosocopy, and this method has been applied to a study of the interaction of polyuridylic acid with purine and adenosine monomers.

The pmr spectra of adenylyl (3' → 5') cytidine (ApC) and cytidylyl (3' → 5') adenosine (CpA) have been studied as a function of concentration and temperature. The results of these studies indicate that the intramolecular base-stacking interactions between the adenine and cytosine bases of these dinucleoside monophosphates are rather strong, and that the stacking tendencies are comparable for the two sequence isomers. The chemical shifts of the cytosine H₅ and adenine H₂ protons, and their variations with temperature, were shown to be consistent with stacked conformations in which both bases of the dinucleoside monophosphates are preferentially oriented in the anti conformation as in similar dApdC, and dCpdA (dA = deoxyadenosine; dC = deoxycytidine) segments in double helical DNA. The intramolecular stacking interaction was found to have a pronounced effect on the conformations of the ribose moieties, and these conformational changes are discussed. The concentration studies indicate extensive self-association of these dinucleoside monophosphates, and analysis of the concentration data facilitated determination of the dimerization constant for the association process as well as the nature of the intermolecular complexes.

The dependence of the ribose conformation upon the extent of intramolecular base-stacking was used to demonstrate that the base-base interaction in cytidylyl (3' → 5') cytidine (CpC) is rather strong, while there appears to be little interaction between the two uracil bases of uridylyl (3' → 5') uridine (UpU).

Studies of the binding of purine to several ribose and deoxyribose dinucleoside monophosphates show that the mode of interaction is base-stacking, and evidence for the formation of a purine-dinucleoside monophosphate intercalated complex is presented. The purine proton resonances are markedly broadened in this complex, and estimates of the purine linewidths in the complex and the equilibrium constant for purine intercalation are obtained.

A study of the interaction of unsubstitued purine with polyuridylic acid at 29°C by pmr indicated that purine binds to the uracil bases of the polymer by base-stacking. The severe broadening of the purine proton resonances observed provides strong evidence for the intercalation of purine between adjacent uracil bases of poly U. This interaction does not result in a more rigid or ordered structure for the polymer.

Investigation of the interaction between adenosine and polyuridylic acid revealed two modes of interaction between the monomer and the polymer, depending on the temperature. At temperatures above 26°C or so, monomeric adenosine binds to poly U by noncooperative A-U base stacking. Below this temperature, a rigid triple-stranded 1A:2U complex is formed, presumably via cooperative hydrogen-bonding as has previously been reported.

These results clearly illustrate the importance of base-stacking in non-specific interactions between bases, nucleosides and nucleotides, and also reveal the important role of the base-stacking interactions in cooperatively for med structures involving specific base-pairing where both types of interaction are possible.

Diego de Moxena, el 'Liber sine nomine' de Petrarca y el concilio de Constanza

Número monográfico dedicado a Petrarca y el humanismo en la Península Ibérica.

A voz e a invocação para musicar a vida: ressonâncias entre música e psicanálise

A articulação entre a psicanálise e a música, mais especificamente a produzida a partir do paradigma de Arnold Schönberg, renovado por John Cage, se mostra emblemática para pensar a constituição do sujeito em Sigmund Freud e Jacques Lacan, bem como para refletir sobre a escuta clínica, o ato analítico enquanto poético, e a escrita pulsional do sujeito como resposta à invocação da voz. O momento de estruturação do sujeito implica a dimensão de musicalidade da linguagem que permite o ato da fala. O sujeito nasce em um ponto em que o significante (simbólico) escreve no real do corpo um possível, um começo, uma marca que invoca uma nota e uma letra, sendo estes os dois aspectos da linguagem: a musicalidade (continuidade) e a fala (descontinuidade em movimento). Este ponto escreve e cria um vazio no sujeito que está e estará sempre em pulsação. Se o real grita caoticamente, é possível que se cante e se musique a vida com a criação de notas singulares, efeito do movimento desejante e de uma escrita pelo circuito da pulsão invocante na partitura já dada pelo Outro e face aos encontros com pedaços de real. A música tem a capacidade de retirar o sujeito de uma surdez de seu próprio desejo, o convocando a recriar a linguagem por seus atos. O paradigma de Schönberg, bem como a música criada a partir deste momento, nos dá a ouvir um saber-fazer com a voz no qual a dimensão equivocante (de equivoco e de invocação) da linguagem pode ressurgir por uma via nova. A transmissão de um saber-fazer com o objeto voz por ele efetuado se apresenta como uma radicalização do efeito de verdade do real, ressoando borromeanamente sobre o simbólico e o imaginário, invocando o momento originário do sujeito, de um começo sempre a recomeçar, que se faz ouvir como uma invocação de musicar a vida de uma maneira ética, estética e poética. É através dos eixos acima expostos que nos é possível sustentar, com Lacan, uma prática clínica orientada para além da repetição em direção a um significante novo. Trata-se de uma orientação que parte dos encontros com o real aos quais o sujeito é confrontado ao acaso visando o movimento renascente pelo qual ele pode re-escutar o inaudito do real contínuo perdido, o que faz com que seu ritmo singular possa ser, uma vez mais e de modo inédito, reinventado. A psicanálise pode ser, portanto, entendida como uma prática invocante, como uma abertura para que o sujeito possa, com entusiasmo, musicar a vida.

Sobre o gozo na clínica psicanalítica com mulheres devastadas

A presente pesquisa sobre o gozo na clínica com mulheres devastadas teve como foco o lugar ocupado pelo gozo em seu aspecto mortífero, de excesso e falta de medida, que se manifesta no âmbito das parcerias amorosas. Partindo das experiências relatadas por algumas analisandas, que as descrevem como "sair do corpo", "ficar louca", "descontrolada" ou "fora de si", e das formulações psicanalíticas a respeito do gozo feminino, buscou-se discutir a questão a partir dos referenciais propostos por Freud e Lacan no que diz respeito à constituição da feminilidade e do feminino, tais como a catástrofe e a devastação na ligação com a mãe e com o parceiro, a forma erotomaníaca de amar, além das duas formas de gozo nas mulheres. Entre os temas abordados nesta dissertação destacam-se as operações da castração e do Complexo de Édipo, juntamente com o seu elemento central, o falo, que permitem trazer à discussão algumas consequências para as mulheres, sobretudo as posições implicadas, a saber: o falo e a mascarada. O conceito de gozo é examinado através de três ser mascarada articulações principais. Primeiramente, a tentativa de Freud, que parece a mais antiga na psicanálise, de circunscrever um gozo propriamente feminino, ligado à satisfação da pulsão pela via da zona vaginal; em segundo lugar, o pensamento de Lacan em Diretrizes para um congresso sobre a sexualidade feminina (1958), em que ele recupera a questão freudiana do congresso sobre a sexualidade feminina gozo feminino, e posteriormente no Seminário 7:a ética da psicanálise (1959-1960), desenvolvido durante o período de preparação para o referido congresso, no qual Lacan eleva o gozo ao estatuto de conceito. Como desdobramento, encontram-se algumas articulações clínicas acerca do gozo devastador nos relacionamentos amorosos, tomando como referência a personagem da Erwartung, op. 17 , de Arnold Schoenberg e as mulheres que encontramos no dia a dia da clínica.

Comparação do Gasto energético de repouso obtido pela calorimetria indireta com as equações de predição em pacientes idosos em tratamento crônico de hemodiálise

Assim como na população geral, as necessidades energéticas diárias dos pacientes em tratamento crônico de hemodiálise (HD) podem ser calculadas multiplicando-se o gasto energético de repouso (GER) pelo nível de atividade física. Até o momento, não há estudos que avaliaram se as equações de predição são precisas para se estimar o GER de idosos em HD. O objetivo do presente estudo foi avaliar a concordância entre o GER obtido pela calorimetria indireta e as equações de predição de Harris&Benedict, Schofield e a proposta pelo documento da Organização Mundial de Saúde de 1985 (FAO 1985) nos pacientes idosos em HD. Tratou-se de um estudo transversal, onde foi avaliado o GER de 57 pacientes idosos não institucionalizados (> 60anos) em tratamento crônico de HD mensurado pela calorimetria indireta e comparado com as equações de predição de Harris&Benedict, Schofield e FAO 1985.A concordância entre o GER medido e as equações foi realizada pelo coeficiente de correlação intraclasse e pela análise de Bland-Altman. Neste estudo pode-se observar que o GER estimado pelas 3 equações foi significantemente maior do que o obtido pela calorimetria indireta. Um grau de reprodutibilidade moderado foi observado entre a calorimetria indireta e as equações. A superestimação foi o principal erro observado, sendo presente na metade dos pacientes. A subestimação foi vista em aproximadamente em 10 % dos pacientes. Com base nesses achados podemos concluir que as 3 equações tiveram uma performance similar ao estimar o GER. E estas podem ser utilizadas para calcular o GER de idosos em HD, na medida em que os nutricionistas reconheçam seus possíveis erros, principalmente quando as equações de predição subestimam o GER medido.

利用分光光度计测量光学晶体的折射率

晶体折射率的准确测定是晶体上薄膜器件设计的基础。介绍了利用分光光度计测量晶体折射率的方法，通过背面影响系数法、背面镀增透膜和将两者结合起来的方法消除晶体反射率测量时背面反射带来的影响，给出了具体的步骤并对测量误差进行了分析。由于晶体的光学各向异性，采用起偏器扫描的方法测量晶体光学性质随方向的变化。通过对LiB3P5晶体的折射率的测量，证实了该方法的可行性并可用于其他光学晶体折射率的测量。