Large pseudoscalar Yukawa couplings in the complex 2HDM

We start by presenting the current status of a complex flavour conserving two-Higgs doublet model. We will focus on some very interesting scenarios where unexpectedly the light Higgs couplings to leptons and to b-quarks can have a large pseudoscalar component with a vanishing scalar component. Predictions for the allowed parameter space at end of the next run with a total collected luminosity of 300 fb(-1) and 3000 fb(-1) are also discussed. These scenarios are not excluded by present data and most probably will survive the next LHC run. However, a measurement of the mixing angle phi(tau), between the scalar and pseudoscalar component of the 125 GeV Higgs, in the decay h -> tau(+)tau(-) will be able to probe many of these scenarios, even with low luminosity. Similarly, a measurement of phi(t) in the vertex (t) over bar th could help to constrain the low tan beta region in the Type I model.

Juggling time concepts: complex metanarrative in Alejandro González Iñárritu’s 21 Grams

ABSTRACT - Starting with the explanation of metanarrative as a sort of self-reflexive storytelling (as defended by Kenneth Weaver Hope in his unpublished PhD. thesis), I propose to talk about enunciative practices that stress the telling more than the told. In line with some metaficcional practices applied to cinema, such as the ‘mindfuck’ film (Jonathan Eig, 2003), the ‘psychological puzzle film’ (Elliot Panek, 2003) and the ‘mind-game film’ (Thomas Elsaesser, 2009), I will address the manipulations that a narrative film endures in order to produce a more fruitful and complex experience for the viewer. I will particularly concentrate on the misrepresentation of time as a way to produce a labyrinthine work of fiction where the linear description of events is replaced by a game of time disclosure. The viewer is thus called upon to reconstruct the order of the various situations portrayed in a process that I call ‘temporal mapping’. However, as the viewer attempts to do this, the film, ironically, because of the intricate nature of the plot and the uncertain status of the characters, resists the attempt. There is a sort of teasing taking place between the film and its spectator: an invitation of decoding that is half-denied until the end, where the puzzle is finally solved. I will use three of Alejandro Iñárritu’s films to better convey my point: Amores perros (2000), 21 Grams (2003) and Babel (2006). I will consider Iñárritu’s methods to produce a non-linear storytelling as a way to stress the importance of time and its validity as one of the elements that make up for a metanarrative experience in films. I will focus especially on 21 Grams, which I consider to be a paragon of the labyrinth.

How Complex, Probable, and Predictable is Genetically Driven Red Queen Chaos?

Coevolution between two antagonistic species has been widely studied theoretically for both ecologically- and genetically-driven Red Queen dynamics. A typical outcome of these systems is an oscillatory behavior causing an endless series of one species adaptation and others counter-adaptation. More recently, a mathematical model combining a three-species food chain system with an adaptive dynamics approach revealed genetically driven chaotic Red Queen coevolution. In the present article, we analyze this mathematical model mainly focusing on the impact of species rates of evolution (mutation rates) in the dynamics. Firstly, we analytically proof the boundedness of the trajectories of the chaotic attractor. The complexity of the coupling between the dynamical variables is quantified using observability indices. By using symbolic dynamics theory, we quantify the complexity of genetically driven Red Queen chaos computing the topological entropy of existing one-dimensional iterated maps using Markov partitions. Co-dimensional two bifurcation diagrams are also built from the period ordering of the orbits of the maps. Then, we study the predictability of the Red Queen chaos, found in narrow regions of mutation rates. To extend the previous analyses, we also computed the likeliness of finding chaos in a given region of the parameter space varying other model parameters simultaneously. Such analyses allowed us to compute a mean predictability measure for the system in the explored region of the parameter space. We found that genetically driven Red Queen chaos, although being restricted to small regions of the analyzed parameter space, might be highly unpredictable.

On similarities in infrared spectra of complex drugs

A chromatographic separation of active ingredients of Combivir, Epivir, Kaletra, Norvir, Prezista, Retrovir, Trivizir, Valcyte, and Viramune is performed on thin layer chromatography. The spectra of these nine drugs were recorded using the Fourier transform infrared spectroscopy. This information is then analyzed by means of the cosine correlation. The comparison of the infrared spectra in the perspective of the adopted similarity measure is possible to visualize with present day computer tools, and the emerging clusters provide additional information about the similarities of the investigated set of complex drugs.

Two-loop stability of a complex singlet extended Standard Model

Motivated by the dark matter and the baryon asymmetry problems, we analyze a complex singlet extension of the Standard Model with a Z(2) symmetry (which provides a dark matter candidate). After a detailed two-loop calculation of the renormalization group equations for the new scalar sector, we study the radiative stability of the model up to a high energy scale (with the constraint that the 126 GeV Higgs boson found at the LHC is in the spectrum) and find it requires the existence of a new scalar state mixing with the Higgs with a mass larger than 140 GeV. This bound is not very sensitive to the cutoff scale as long as the latter is larger than 10(10) GeV. We then include all experimental and observational constraints/measurements from collider data, from dark matter direct detection experiments, and from the Planck satellite and in addition force stability at least up to the grand unified theory scale, to find that the lower bound is raised to about 170 GeV, while the dark matter particle must be heavier than about 50 GeV.

The Sinemurian ammonites of the Lusitanian Basin (Portugal): an example of complex endemic evolutioin

Palaeodiversity 3: 59–87; Stuttgart 30 December 2010

Immune reconstitution after autologous hematopoietic stem cell transplantation

Abstract The investigation of the web of relationships between the different elements of the immune system has proven instrumental to better understand this complex biological system. This is particularly true in the case of the interactions between B and T lymphocytes, both during cellular development and at the stage of cellular effectors functions. The understanding of the B–T cells interdependency and the possibility to manipulate this relationship may be directly applicable to situations where immunity is deficient, as is the case of cancer or immune suppression after radio and chemotherapy. The work presented here started with the development of a novel and accurate tool to directly assess the diversity of the cellular repertoire (Chapter III). Contractions of T cell receptor diversity have been related with a deficient immune status. This method uses gene chips platforms where nucleic acids coding for lymphocyte receptors are hybridized and is based on the fact that the frequency of hybridization of nucleic acids to the oligonucleotides on a gene chip varies in direct proportion to diversity. Subsequently, and using this new method and other techniques of cell quantification I examined, in an animal model, the role that polyclonal B cells and immunoglobulin exert upon T cell development in the thymus, specifically on the acquisition of a broader repertoire diversity by the T cell receptors (Chapter IV and V). The hypothesis tested was if the presence of more diverse peptides in the thymus, namely polyclonal immunoglobulin, would induce the generation of more diverse T cells precursors. The results obtained demonstrated that the diversity of the T cell compartment is increased by the presence of polyclonal immunoglobulin. Polyclonal immunoglobulin, and particularly the Fab fragments of the molecule, represent the most diverse self-molecules in the body and its peptides are presented by antigen presenting cells to precursor T cells in the thymus during its development. This probably contributes significantly to the generation of receptor diversity. Furthermore, we also demonstrated that a more diverse repertoire of T lymphocytes is associated with a more effective and robust T cell immune function in vivo, as mice with a more diverse T cell receptors reject minor histocompatiblility discordant skin grafts faster than mice with a shrunken T cell receptor repertoire (Chapter V). We believe that a broader T cell receptor diversity allows a more efficient recognition and rejection of a higher range of external and internal aggressions. In this work it is demonstrated that a reduction of TCR diversity by thymectomy in wild type mice significantly increased survival of H-Y incompatible skin grafts, indicating decrease on T cell function. In addiction reconstitution of T-cell diversity in mice with a decreased T cell repertoire diversity with immunoglobulin Fab fragments, lead to a increase on TCR diversity and to a significantly decreased survival of the skin grafts (Chapter V). These results strongly suggest that increases on T cell repertoire diversity contribute to improvement of T cell function. Our results may have important implications on therapy and immune reconstitution in the context of AIDS, cancer, autoimmunity and post myeloablative treatments. Based on the previous results, we tested the clinical hypothesis that patients with haematological malignancies subjected to stem cell transplantation who recovered a robust immune system would have a better survival compared to patients who did not recover such a robust immune system. This study was undertaken by the examination of the progression and overall survival of 42 patients with mantle cell non-Hodgkin lymphoma receiving autologous hematopoietic stem cell transplantation (Chapter VI). The results obtained show that patients who recovered higher numbers of lymphocytes soon after autologous transplantation had a statistically significantly longer progression free and overall survivals. These results demonstrate the positive impact that a more robust immune system reconstitution after stem cell transplantation may have upon the survival of patients with haematological malignancies. In a similar clinical research framework, this dissertation also includes the study of the impact of recovering normal serum levels of polyclonal immunoglobulin on the survival of patients with another B cell haematological malignancy, multiple myeloma, after autologous stem cell transplantation (Chapter VII). The relapse free survival of the 110 patients with multiple myeloma analysed was associated with their ability to recover normal serum levels of the polyclonal compartment of immunoglobulin. These results suggest again the important effect of polyclonal immunoglobulin for the (re)generation of the immune competence. We also studied the impact of a robust immunity for the response to treatment with the antibody anti CD20, rituximab, in patients with non- Hodgkin’s lymphoma (NHL) (Chapter VIII). Patients with higher absolute counts of CD4+ T lymphocytes respond better (in terms of longer progression free survival) to rituximab compared to patients with lower number of CD4+ T lymphocytes. These observations highlight again the fact that a competent immune system is required for the clinical benefit of rituximab therapy in NHL patients. In conclusion, the work presented in this dissertation demonstrates, for the first time, that diverse B cells and polyclonal immunoglobulin promote T cell diversification in the thymus and improve T lymphocyte function. Also, it shows that in the setting of immune reconstitution, as after autologous stem cell transplantation for mantle cell lymphoma and in the setting of immune therapy for NHL, the absolute lymphocyte counts are an independent factor predicting progression free and overall survival. These results can have an important application in the clinical practice since the majority of the current treatments for cancer are immunosuppressive and implicate a subsequent immune recovery. Also, the effects of a number of antineoplastic treatments, including biological agents, depend on the immune system activity. In this way, studies similar to the ones presented here, where methods to improve the immune reconstitution are examined, may prove to be instrumental for a better understanding of the immune system and to guide more efficient treatment options and the design of future clinical trials. Resumo O estudo da rede de inter-relações entre os diversos elementos do sistema immune tem-se mostrado um instrumento essencial para uma melhor compreensão deste complexo sistema biológico. Tal é particularmente verdade no caso das interacções entre os linfócitos B e T, quer durante o desenvolvimento celular, quer ao nível das funções celulares efectoras. A compreensão da interdependência entre linfócitos B e T e a possibilidade de manipular esta relação pode ser directamente aplicável a situações em que a imunidade está deficiente, como é o caso das doenças neoplásicas ou da imunossupressão após radio ou quimioterapia. O trabalho apresentado nesta dissertação iniciou-se com o desenvolvimento de um novo método laboratorial para medir directamente a diversidade do reportório celular (Capítulo III). Reduções da diversidade do reportório dos receptores de células T têm sido relacionadas com um estado de imunodeficiência. O método desenvolvido utiliza “gene chips”, aos quais hibridizam os ácidos nucleicos codificantes das cadeias proteicas dos receptores linfocitários. A diversidade é calculada com base na frequência de hibridização do ácido nucleico da amostra aos oligonucleótidos presentes no “gene chip”. De seguida, e utilizando este novo método e outras técnicas de quantificação celular examinei, num modelo animal, o papel que as células policlonais B e a imunoglobulina exercem sobre o desenvolvimento linfocitário T no timo, especificamente na aquisição de um reportório diverso de receptores T (Capítulos IV e V). Testei, então, a hipótese de que a presença no timo de péptidos mais diversos, como a imunoglobulna policlonal, induzisse a génese de precursores T mais diversos. Demonstrámos que a diversidade do compartimento T é aumentado pela presença de imunoglobulina policlonal. A imunoglobulina policlonal, e particularmente os fragmentos Fab desta molécula, representam as moléculas autólogas mais diversas presentes nos organismos vertebrados. Estes péptidos são apresentados por células apresentadoras de antigénio às células precursoras T no timo, durante o desenvolvimento celular T. Tal, provavelmente, contribui para a génese da diversidade dos receptores. Também demonstrámos que a presença de um reportório mais diverso de linfócitos T se associa a um incremento da função imunológica T in vivo. Uma diversidade de receptores T mais extensa parece permitir um reconhecimento e rejeição mais eficientes de um maior número de agressores internos e externos. Demonstrámos que ratinhos com receptores de células T (RCT) com maior diversidade rejeitam transplantes cutâneos discordantes para antigénios minor de histocompatibilidade mais rapidamente do que ratinhos com um menor reportório T (Capítulo V). Por outro lado, uma redução da diversidade do RCT, causada por timectomia de ratinhos de estirpes selvagens, mostrou aumentar significativamente a sobrevivência de transplantes cutâneos incompatíveis para o antigénio H-Y (antigénio minor de histocompatibilidade), indicando uma diminuição da função linfocitária T. Além disso, a reconstituição da diversidade dos linfócitos T em ratinhos com uma diversidade de reportório T diminuída, induzida pela administração de fragmentos Fab de imunoglobulina, conduz a um aumento da diversidade dos RCT e a uma diminuição significativa da sobrevivência dos enxertos cutâneos (Capítulo V). Estes resultados sugerem que o aumento do reportório de células T contribui para uma melhoria das funções celulares T e poderão ter implicações importantes na terapêutica e reconstitutição imunológica em contexto de SIDA, neoplasias, autoimunidade e após tratamentos mieloablativos. Baseado nos resultados anteriores, decidimos testar a hipótese clínica de que doentes com neoplasias hematológicas sujeitos a transplantação de precursores hematopoiéticos e com recuperação imunológica precoce após transplante teriam uma sobrevivência mais longa do que doentes que não recuperassem tão bem a sua imunidade. Analisámos a sobrevivência global e sobrevivência sem doença de 42 doentes com linfoma não Hodgkin de células do manto sujeitos a transplante autólogo de precursores hematopoiéticos (Capítulo VI). Os resultados obtidos mostraram que os doentes que recuperaram contagens mais elevadas de linfócitos imediatamente após o transplante autólogo, apresentaram uma sobrevivência global e sem progressão mais longa do que doentes que não recuperaram contagens linfocitárias tão precocemente. Estes resultados demonstram o efeito positivo de uma reconstitutição imunológica robusta após transplante de presursores hematopoiéticos, sobre a sobrevivência de doentes com neoplasias hematológicas. Do mesmo modo, estudámos o efeito que a recuperação de níveis séricos normais de imunoglobulina policlonal tem na sobrevivência de doentes com outras neoplasias hematológicas de linfócitos B, como o mieloma múltiplo,após transplante autólogo de precursos hematopoiéticos (Capítulo VII). A sobrevivência livre de doença dos 110 doentes com mieloma múltiplo analizados está associada com a sua capacidade de recuperar níveis séricos normais do compartmento policlonal de imunoglobulina. Estes resultados pioneiros indicam a importância da imunoglobulina policlonal para a génese de competência imunológica. Também estudámos o impacto de um sistema imunitário eficiente sobre a resposta ao tratamento com o anticorpo anti CD20, ituximab, em doentes com linfoma não Hodgkin (LNH) (Capítulo VIII). Os resultados mostram que doentes com valores mais elevados de linfócitos T CD4+ respondem melhor (em termos de maior sobrevida livre de doença) ao rituximab, do que doentes com valores mais baixos. Estas observações ilustram a necessidade de um sistema imunitário competente para o benefício clínico da terapêutica com rituximab em doentes com LNH. Em conclusão, o trabalho apresentado nesta dissertação demonstra que as células B e a imunoglobulina policlonal promovem a diversidade das células T no timo e melhoram a função linfocitária T periférica. Concomitantemente, também demonstrámos que, no contexto de reconstituição imune, por exemplo, após transplante autólogo de precursores hematopoiéticos em doentes com linfomas de células do manto, o número absoluto de linfócitos é uma factor independente da sobrevivência. Os resultados demonstram, também, a importância dos valores de linfocitos T na resposta ao tratamento com rituximab no caso de doentes com LNH. O mesmo princípio se prova pelo facto de que doentes com mieloma múltiplo sujeitos a transplante autólogo de precursores hematopoiéticos que recuperam valores normais séricos de imunoglobulinas policlonais, terem melhores taxas de resposta em comparação com doentes que não recuperam valores normais de imunoglobulinas policlonais. Estes resultados podem ter importantes aplicações na prática clínica dado que a maioria dos tratamentos de doenças neoplásicas implica imunossupressão e, subsequente, recuperação imunológica. Estes estudos podem ser um instrumento fundamental para uma melhor compreensão do sistema imune e guiar uma escolha mais eficiente de opções terapêuticas bem como contribuir para a concepção de futuros estudos clínicos.

Estudo comparativo do LCR de pacientes com neurocriptococose sem AIDS e com AIDS

Até a década de 80, antes do surgimento da AIDS, a criptococose era relativamente rara. Verificou-se que esta doença afeta muito frequentemente os pacientes com AIDS e pode ser a primeira manifestação desta síndrome. O objetivo deste trabalho é o de comparar o resultado dos exames das amostras do LCR inicial na meningencefalite por criptococo entre pacientes com e sem AIDS. Este trabalho é baseado no estudo de 41 pacientes com neurocriptococose sem AIDS e de 23 pacientes com neurocriptococose e AIDS. Este estudo permitiu verificar que a reação inflamatória, no sistema nervoso, quando presente, foi de menor intensidade nos pacientes com AIDS; a reação inflamatória esteve presente em todos os pacientes sem AIDS e ausente em 21,7% dos pacientes com AIDS; o quadro inflamatório crônico, semelhante ao da meningencefalite tuberculosa, clássico nas meningencefalites por criptococo, ocorreu raramente nos pacientes com AIDS; em média, o número de criptococos no LCR foi maior nos pacientes com AIDS; pode ser feito diagnóstico presuntivo da AIDS quando o criptococo estiver presente no LCR que não apresenta alterações citológicas e bioquímicas.

The alternative complex III from Rhodothermus marinus - a prototype of a new family of quinol: electron acceptor oxidoreductase

Dissertation presented to obtain a PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Energy transduction by respiratory complex I

Dissertation presented to obtain a PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Visceral leishmaniasis and Acquired Immunodeficiency Sydrome (AIDS): case report

This is a case report that describe an association of AIDS, visceral leishmaniasis and probable disseminated tuberculosis. Due to the spread of AIDS in developing areas worldwide this association would be more frequently, seen on subjects from endemic areas where this protozoonosis is prevalent. More than one opportunistic infection related with the endemic diseases of the developing regions can be associated with those immunocompromised patients.

Usefulness of the detection of Toxoplasma gondii antigens in AIDS patients

Toxoplasmic encephalitis (TE) is a mayor cause of central nervous system infection in patients with acquired immunodeficiency syndrome (AIDS). Toxoplasma antibodies were detected in 56 of 79 patients with AIDS (71%), in the present study. Fourteen out of 57 seropositive patients developed TF (25%) and had Toxoplasma gondii antigen detected in their urine. For this, most of them received an effective therapy, with the subsequent disappearance of the symptoms and discontinuity of excretion of the T. gondii antigens. Our results suggest that the monitoring of T. gondii antigen in the urine of AIDS patients may be useful to decide on the proper time for therapy, as well as to avoid the beginning of neurologic signs in these patients.

Drug resistance of M. Tuberculosis isolated from patients with HIV infection seen at an AIDS Reference Center in São Paulo, Brazil

M. tuberculosis-positive cultures were obtained from 228 patients seen in our service and drug sensitivity assays were carried out from January 1992 to December 1994. A survey of the medical records of these patients showed resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported previous treatment, were considered to have acquired resistance. Among the antecedents investigated, only previous treatment and alcoholism were the factors independently associated with the occurrence of resistance. The survival of patients with resistant strains was lower than that of patients attacked by non-resistant M. tuberculosis. We conclude that in the present series M. tuberculosis resistance to tuberculostatic agents was predominantly of the acquired type.

Gastrointestinal translocation as a possible source of candidemia in an AIDS patient

Apart from cryptococcosis and histoplasmosis, which are mycoses contained by T cell-mediated mechanisms of host defense, fungemia is rarely found in AIDS patients. The frequency of fungemia due to Candida spp. has been reported to be as low as 1 %. We report a non-neutropenic AIDS patient who presented a candidemia which probably arose from her gastrointestinal tract.

Development of Secondary Resistance to Fluconazole in Cryptococcus neoformans Isolated from a Patient with AIDS

Cryptococcus neoformans is the fifth most common opportunistic agent of infection in patients with AIDS in the USA, exceeded only by Candida species, Pneumocystis carinii, cytomegalovirus and Mycobacterium avium1, 2, 6, 10, 11. In Brazil is the sixth, exceeded by Candida species, P. carinii, Mycobacterium species, Toxoplasma gondii, and herpes simplex virus (AIDS, Boletim Epidemiológico, set/nov 96, Ministério da Saúde, Brasil). During 30 years, the treatment of C. neoformans meningitis was based on the use of amphotericin B with or without flucytosine13. Nowadays, with the immunodepression caused by human immunodeficiency virus (HIV) infection and the availability of new antifungal drugs as the triazoles, the concept related to cure and relapses of cryptococcosis has been altered7, 20. Patients are treated with amphotericin B with or without flucytosine as initial therapy, but maintenance therapy is always necessary in AIDS patients with C. neoformans infections