2,4-Dioxa-λ6-thia­tetra­cyclo­[5.3.1.15,9.01,5]dodecane-3,3-dione

The crystal structure of the title compound, C9H12O4S, was determined in order to investigate the effect of the eclipsed O atoms on the bond length of the vicinal quaternary C atoms. The two quaternary C atoms of the noradamantane skeleton and the two O atoms to which they are connected all located essentially in the same plane (maximum deviation = 0.01 Å), resulting in an eclipsed conformation of the C—O bonds. The C—C bond of the quaternary C atoms is 1.581 (3) Å, considerably longer than the other C—C bonds of the mol­ecule due to the stretch of the cage structure

Multi-descriptional physicalism, level(s) of being, and the mind-body problem

The main idea of this thesis is multi-descriptional physicalism. According to it, only physical entities are elements of our ontology, and there are different ways to describe them. Higher-level vocabularies (e.g., mental, neurological, biological) truly describe reality. Sentences about higher-level entities are made true by physical entities. Every chapter will develop multi-descriptional physicalism or defend it from objections. In chapter 1, I will propose a new conceptual reductive account that conceptually reduces higher-level entities to physical entities. This conceptual reductive account combines resources from Heil’s truthmaker theory and either a priori physicalism or a posteriori physicalism. In chapter 2, I apply this conceptual reductive account to various debates. Physicalism, the multiple-realisability argument, the prototype theory of concepts, and truthmaker explanations will be discussed. In chapter 3, I will argue that a major aim of metaphysics should be to discover which entities are fundamental and explain why they suffice for the existence of derivative entities. In chapter 4, I will propose a new way to explain why sentences apparently about composite objects are true even though there are no composite objects. It combines resources from Cameron’s truthmaker theory and van Inwagen’s paraphrase strategy. In chapter 5, I will argue that the intuition that the mind and the body are very different does not show that the mind is distinct from the body. This intuition can be explained away by mentioning our dispositions to give non-physical explanations when we are ignorant of physical facts. In chapter 6, I will examine two arguments for the existence of a metaphysically independent level, and I will argue that only a modified version of one of them succeeds. I will argue that methodological principles support the view that there is a metaphysically independent level

HelioTrope: An innovative and efficient prototype for solar power production

The solar energy alternative could provide us with all the energy we need as it exist in vast quantities all around us. We only should be innovative enough in order to improve the efficiency of our systems in capturing and converting solar energy in usable forms of power. By making a case for the solar energy alternative, we identify areas where efficiency can be improved and thereby Solar Energy can become a competitive energy source. This paper suggests an innovative approach to solar energy power production, which is manifested in a prototype given the name HelioTrope. The Heliotrope Solar Energy Production prototype is tested on its' capabilities to efficiently covert solar energy to generation of electricity and other forms of energy for storage or direct use. HelioTrope involves an innovative Stirling engine design and a parabolic concentrating dish with a sun tracking system implementing a control algorithm to maximize the capturing of solar energy. Further, it utilizes a patent developed by the authors where a mechanism is designed for the transmission of reciprocating motion of variable amplitude into unidirectional circular motion. This is employed in our prototype for converting linear reciprocating motion into circular for electricity production, which gives a significant increase in efficiency and reduces maintenance costs. Preliminary calculations indicate that the Heliotrope approach constitutes a competitive solution to solar power production

Tricyclo­[3.3.1.03,7]nonane-3,7-diyl bis­(methane­sulfonate)

The crystal structure of the title compound, C11H18O6S2, was determined to investigate the effect of the eclipsed mesyl groups on the bond length of the vicinal quaternary C atoms. The two quaternary C atoms of the noradamantane skeleton and the two O atoms to which they are connected all located essentially in the same plane [maximum deviation 0.01 Å], resulting in an eclipsing conformation of the C—O bonds. The C—C bond of the quaternary C atoms is 1.597 (3) Å is considerably longer than the other C—C bonds of the mol­ecule

Fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan contributes to the diagnosis and management of brucellar spondylodiskitis

BACKGROUND: Limited data suggest that fluorine-18 fluoro-2-deoxy-D-glucose (F-18 FDG) positron emission tomography combined with computed tomography (PET/CT) scan may be useful for diagnosing infections of the spine. Brucellar spondylodiskitis might be devastating and current imaging techniques lack sensitivity and specificity. The aim of this prospective study was to determine the role of F-18 FDG PET/CT scan in the diagnosis of brucellar spondylodiskitis and in monitoring the efficacy of its treatment. METHODS: Ten consecutive patients with brucellar spondylitis were prospectively evaluated with PET/CT. Baseline evaluation included also magnetic resonance imaging (MRI) of the affected spine, indices of inflammation, the slide agglutination test (SAT), and the standard hematology and biochemistry. All cases were treated with suitable antibiotics until resolution or significant improvement of clinical and radiological (MRI) findings. Upon completion of treatment, they were re-evaluated with follow-up PET/CT scan. The maximum standardized uptake values (SUV) were measured and compared with SAT. RESULTS: In all patients there was an increased F-18 FDG activity in the infected spine region detected by the initial MRI. F-18 FDG PET/CT provided additional information, compared to MRI, in 4 (40%) patients. More specifically it revealed additional spine lesions (in 3 patients), lymphadenitis, arthritis, organomegaly, as well as new paravertebral soft tissue involvement and epidural masses. This additional information had an impact on the duration of treatment in these patients. At the end of treatment all patients had a complete clinical response; 5 patients had positive serology, 6 patients had residual MRI findings, while 9 had a positive PET/CT but with significantly decreased FDG uptake compared to baseline (median 2.6, range 1.4 – 4.4 vs. median 5.5, range 2.8 – 9.4, p = 0.005). During the follow up period (median 12.5 months) no relapses have been observed. No significant association was observed between the SUV and SAT. CONCLUSIONS: Our study suggests that in patients with brucellar spondylodiskitis F-18 FDG PET/CT scan can provide additional information on the spread of the infection, compared to MRI. Successful treatment is associated with a significant decrease in SUVmax values; thus, PET/CT scan may be a complementary method for determining the efficacy of treatment

DNA-induced spatial entrapment of general transcription machinery can stabilize gene expression in a nondividing cell.

Funder: Wellcome TrustAn important characteristic of cell differentiation is its stability. Only rarely do cells or their stem cell progenitors change their differentiation pathway. If they do, it is often accompanied by a malfunction such as cancer. A mechanistic understanding of the stability of differentiated states would allow better prospects of alleviating the malfunctioning. However, such complete information is yet elusive. Earlier experiments performed in Xenopus oocytes to address this question suggest that a cell may maintain its gene expression by prolonged binding of cell type-specific transcription factors. Here, using DNA competition experiments, we show that the stability of gene expression in a nondividing cell could be caused by the local entrapment of part of the general transcription machinery in transcriptionally active regions. Strikingly, we found that transcriptionally active and silent forms of the same DNA template can stably coexist within the same nucleus. Both DNA templates are associated with the gene-specific transcription factor Ascl1, the core factor TBP2, and the polymerase II (Pol-II) ser5 C-terminal domain (CTD) phosphorylated form, while Pol-II ser2 CTD phosphorylation is restricted to the transcriptionally dominant template. We discover that the active and silent DNA forms are physically separated in the oocyte nucleus through partition into liquid-liquid phase-separated condensates. Altogether, our study proposes a mechanism of transcriptional regulation involving a spatial entrapment of general transcription machinery components to stabilize the active form of a gene in a nondividing cell

Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation.

Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways.Herchel Smith Fellowship, Funai Foundation scholarship, Austrian Science Fun

Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation

Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways

High-resolution live cell imaging to define ultrastructural and dynamic features of the halotolerant yeast Debaryomyces hansenii

Although some budding yeasts have proved tractable and intensely studied models, others are more recalcitrant. Debaryomyces hansenii, an important yeast species in food and biotechnological industries with curious physiological characteristics, has proved difficult to manipulate genetically and remains poorly defined. To remedy this, we have combined live cell fluorescent dyes with high-resolution imaging techniques to define the sub-cellular features of D. hansenii, such as the mitochondria, nuclei, vacuoles and the cell wall. Using these tools, we define biological processes like the cell cycle, organelle inheritance and various membrane trafficking pathways of D. hansenii for the first time. Beyond this, reagents designed to study Saccharomyces cerevisiae proteins were used to access proteomic information about D. hansenii. Finally, we optimised the use of label-free holotomography to image yeast, defining the physical parameters and visualising sub-cellular features like membranes and vacuoles. Not only does this work shed light on D. hansenii but this combinatorial approach serves as a template for how other cell biological systems, which are not amenable to standard genetic procedures, can be studied

Aplastic anemia associated with interferon alpha 2a in a patient with chronic hepatitis C virus infection: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hepatitis-associated aplastic anemia is a common syndrome in patients with bone marrow failure. However, hepatitis-associated aplastic anemia is an immune-mediated disease that does not appear to be caused by any of the known hepatitis viruses including hepatitis C virus. In addition, to the best of our knowledge there are no reported cases of patients with chronic hepatitis C virus infection developing aplastic anemia associated with pegylated interferon alpha 2a treatment.</p> <p>Case presentation</p> <p>We report the case of a 46-year-old Greek man who developed severe aplastic anemia during treatment with pegylated interferon alpha 2a for chronic hepatitis C virus infection. He presented with generalized purpura and bruising, as well as pallor of the skin and mucous membranes. His blood tests showed pancytopenia. He underwent allogeneic bone marrow transplantation after completing two courses of immunosuppressive therapy with antithymocyte globulin and cyclosporin A.</p> <p>Conclusions</p> <p>The combination of a specific environmental precipitant represented by the hepatitis C virus infection, an altered metabolic detoxification pathway due to treatment with pegylated interferon alpha 2a and a facilitating genetic background such as polymorphism in metabolic detoxification pathways and specific human leukocyte antigen genes possibly conspired synergistically in the development of aplastic anemia in this patient. Our case clearly shows that the causative role of pegylated interferon alpha 2a in the development of aplastic anemia must not be ignored.</p