105 research outputs found

    Time in Quantum Mechanics and Quantum Field Theory

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    W. Pauli pointed out that the existence of a self-adjoint time operator is incompatible with the semibounded character of the Hamiltonian spectrum. As a result, people have been arguing a lot about the time-energy uncertainty relation and other related issues. In this article, we show in details that Pauli's definition of time operator is erroneous in several respects.Comment: 20 page

    Chapter 3: Pathophysiology

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    The hallmark pathophysiologic feature of dilated cardiomyopathy is systolic dysfunction. Several pathogenetic mechanisms appear to be operative. These include increased hemodynamic overload, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis, and genetic mutations. Although beneficial in the early stages of heart failure, these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Genetic causes account for 30\u201340% of DCM and involve genes that encode a heterogeneous group of molecules that participate in force generation, force transmission, sarcomere integrity, cytoskeletal and nuclear architecture, electrolyte homeostasis, mitochondrial function, and transcription. Additional research will improve our understanding of the complex and longitudinal molecular changes that lead from gene mutation to clinical expressio

    Anticancer prodrugs of butyric acid and formaldehyde protect against doxorubicin-induced cardiotoxicity

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    Formaldehyde has been previously shown to play a dominant role in promoting synergy between doxorubicin (Dox) and formaldehyde-releasing butyric acid (BA) prodrugs in killing cancer cells. In this work, we report that these prodrugs also protect neonatal rat cardiomyocytes and adult mice against toxicity elicited by Dox. In cardiomyocytes treated with Dox, the formaldehyde releasing prodrugs butyroyloxymethyl diethylphosphate (AN-7) and butyroyloxymethyl butyrate (AN-1), but not the corresponding acetaldehyde-releasing butyroyloxydiethyl phosphate (AN-88) or butyroyloxyethyl butyrate (AN-11), reduced lactate dehydrogenase leakage, prevented loss of mitochondrial membrane potential (ΔΨm) and attenuated upregulation of the proapoptotic gene Bax. In Dox-treated mice, AN-7 but not AN-88 attenuated weight-loss and mortality, and increase in serum lactate dehydrogenase. These findings show that BA prodrugs that release formaldehyde and augment Dox anticancer activity also protect against Dox cardiotoxicity. Based on these observations, clinical applications of these prodrugs for patients treated with Dox warrant further investigation

    Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

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    Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de ClΓ­nicas de Porto Alegre - Rio Grande do Sul, Brazil

    Gendered dimensions of obesity in childhood and adolescence

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    BACKGROUND: The literature on childhood and adolescent obesity is vast. In addition to producing a general overview, this paper aims to highlight gender differences or similarities, an area which has tended not to be the principal focus of this literature. METHODS: Databases were searched using the terms 'obesity' and 'child', 'adolescent', 'teenager', 'youth', 'young people', 'sex', 'gender', 'masculine', 'feminine', 'male', 'female', 'boy' and 'girl' (or variations on these terms). In order to limit the potential literature, the main focus is on other reviews, both general and relating to specific aspects of obesity. RESULTS: The findings of genetic studies are similar for males and females, and differences in obesity rates as defined by body mass index are generally small and inconsistent. However, differences between males and females due to biology are evident in the patterning of body fat, the fat levels at which health risks become apparent, levels of resting energy expenditure and energy requirements, ability to engage in certain physical activities and the consequences of obesity for the female reproductive system. Differences due to society or culture include food choices and dietary concerns, overall physical activity levels, body satisfaction and the long-term psychosocial consequences of childhood and adolescent obesity. CONCLUSION: This review suggests differences between males and females in exposure and vulnerability to obesogenic environments, the consequences of child and adolescent obesity, and responses to interventions for the condition. A clearer focus on gender differences is required among both researchers and policy makers within this field

    The subunit structure of mouse iga.

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