1,696 research outputs found

    Rights in geospatial information: A shifting legal terrain

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    © 2017 Melbourne University Law Review. All rights reserved. The growing significance of 'big data' raises new issues for copyright law, not least when the data is presented visually or graphically to generate new and useful information and insights. One such example is the case of digital maps. Maps and written descriptions of geographic information have long presented challenges for the law of copyright, most particularly because they are perceived as factual compilations. The appearance of maps, and the information they contain, has changed considerably over time. However, the last few years has seen an extraordinary transformation in the methods and practices of collecting, storing, representing and disseminating geospatial data and information. This article considers how copyright law applied in the analogue era to regulate the production and dissemination of geographic information, the effects of new technologies and digitisation on how law applies to geospatial data and associated products and systems, and whether either a database right or some other form of protection is required

    The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model

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    2-Methoxyestradiol is one of the natural 17β-estradiol derivatives and a potential novel anticancer agent currently being under evaluation in advanced phases of clinical trials. However, the mechanism of anticancer action of 2-methoxyestradiol has not been yet fully established. In our previous studies we have demonstrated that 2-methoxyestradiol selectively induces the expression and nuclear translocation of neuronal nitric oxide synthase in osteosarcoma 143B cells. Heat shock proteins (Hsps) are factors involved in the regulation of expression and activity of nitric oxide synthases. Herein, we chose osteosarcoma cell lines differed in metastatic potential, metastatic 143B and highly metastatic MG63.2 cells, in order to further investigate the anticancer mechanism of 2-methoxyestradiol. The current study aimed to determine the role of major heat shock proteins, Hsp90 and Hsp70 in 2-methoxyestradiol-induced osteosarcoma cell death. We focused on the implication of Hsp90 and Hsp70 in control under expression of neuronal nitric oxide synthase, localization of the enzyme, and further generation of nitro-oxidative stress. To give the insight into the role of Hsp90 in regulation of anticancer efficacy of 2-methoxyestradiol, we used geldanamycin as a potent Hsp90 inhibitor. Herein, we evidenced that inhibition of Hsp90 controls the protein expression of 2-methoxyestradiol-induced neuronal nitric oxide synthase and inhibits enzyme nuclear translocation. We propose that decreased level of neuronal nitric oxide synthase protein after a combined treatment with 2-methoxyestradiol and geldanamycin is directly associated with the accompanying upregulation of Hsp70 and downregulation of Hsp90. This interaction resulted in abrogation of anticancer efficacy of 2-methoxyestradiol by geldanamycin

    Are the adverse effects of glitazones linked to induced testosterone deficiency?

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    <p>Abstract</p> <p>Background</p> <p>Adverse side-effects of the glitazones have been frequently reported in both clinical and animal studies, especially with rosiglitazone (RGZ) and pioglitazone (PGZ), including congestive heart failure, osteoporosis, weight gain, oedema and anaemia. These led to consideration of an evidence-based hypothesis which would explain these diverse effects, and further suggested novel approaches by which this hypothesis could be tested.</p> <p>Presentation of hypothesis</p> <p>The literature on the clinical, metabolic and endocrine effects of glitazones in relation to the reported actions of testosterone in diabetes, metabolic syndrome, and cardiovascular disease is reviewed, and the following unifying hypothesis advanced: "<it>Glitazones induce androgen deficiency in patients with Type 2 Diabetes Mellitus resulting in pathophysiological changes in multiple tissues and organs which may explain their observed clinical adverse effects</it>." This also provides further evidence for the lipocentric concept of diabetes and its clinical implications.</p> <p>Testing of the hypothesis</p> <p>Clinical studies to investigate the endocrine profiles, including measurements of TT, DHT, SHBG, FT and estradiol, together with LH and FSH, in both men and women with T2DM before and after RGZ and PGZ treatment in placebo controlled groups, are necessary to provide data to substantiate this hypothesis. Also, studies on T treatment in diabetic men would further establish if the adverse effects of glitazones could be reversed or ameliorated by androgen therapy. Basic sciences investigations on the inhibition of androgen biosynthesis by glitazones are also warranted.</p> <p>Implications of the hypothesis</p> <p>Glitazones reduce androgen biosynthesis, increase their binding to SHBG, and attenuate androgen receptor activation, thus reducing the physiological actions of testosterone, causing relative and absolute androgen deficiency. This hypothesis explains the adverse effects of glitazones on the heart and other organs resulting from reversal of the action of androgens in directing the maturation of stem cells towards muscle, vascular endothelium, erythroid stem cells and osteoblasts, and away from adipocyte differentiation. The higher incidence of side-effects with RGZ than PGZ, may be explained by a detailed study of the mechanism by which glitazones down-regulate androgen biosynthesis and action, resulting in a state of androgen deficiency.</p

    Combining frequency and time domain approaches to systems with multiple spike train input and output

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    A frequency domain approach and a time domain approach have been combined in an investigation of the behaviour of the primary and secondary endings of an isolated muscle spindle in response to the activity of two static fusimotor axons when the parent muscle is held at a fixed length and when it is subjected to random length changes. The frequency domain analysis has an associated error process which provides a measure of how well the input processes can be used to predict the output processes and is also used to specify how the interactions between the recorded processes contribute to this error. Without assuming stationarity of the input, the time domain approach uses a sequence of probability models of increasing complexity in which the number of input processes to the model is progressively increased. This feature of the time domain approach was used to identify a preferred direction of interaction between the processes underlying the generation of the activity of the primary and secondary endings. In the presence of fusimotor activity and dynamic length changes imposed on the muscle, it was shown that the activity of the primary and secondary endings carried different information about the effects of the inputs imposed on the muscle spindle. The results presented in this work emphasise that the analysis of the behaviour of complex systems benefits from a combination of frequency and time domain methods

    Distribution of the DAZ gene transcripts in human testis.

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    Involvement of variety of genes, especially located on Y chromosome, is critical for the regulation of spermatogenesis. In particular, fertility candidate genes such as deleted in azoospermia (DAZ) are believed to have important function in sperm production, since DAZ is frequently deleted in azoospermic and severy oligozoospermic men. The role of the DAZ gene is supported by its exclusive expression in the testis and by its deletion in about 10% of azoospermic and severely oligozoospermic patients. The distribution of DAZ transcripts in seminiferous epithelium of human testis is reported in the present study. The use of Adobe Photoshop and Scion Image softwares allowed for semi-quantitative analysis of in situ RT-PCR (ISRT-PCR) results. The intensity of ISRT-PCR product's fluorescence was different within individual seminiferous tubules. It was clearly shown by using the pseudocolour scale and transforming the intensity of the fluorescence into levels of greyscale images. The more intense fluorescence characterised single spermatogonia and those organized in small groups inside separate tubules. The most intense accumulation of DAZ mRNA was observed in spermatogonia

    Clinical profile and management of outpatients with non-ischemic and non-hypertensive systolic heart failure: Analysis of the Polish DATA-HELP registry

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    Background: Although coronary artery disease and arterial hypertension are the most common etiologies underlying heart failure (HF), there are still many patients present with non-ischemic and non-hypertensive HF whose management remains very challenging. In this research study the clinical profile and applied treatment of patients with HF without coronary artery disease or hypertension versus patients with known etiology of HF (ischemic/hypertensive) were compared. Methods: Clinical data about 5563 patients with stable systolic HF were obtained from prospective multicenter DATA-HELP registry performed between October and December 2009 in ambulatory clinics in Poland, in which 500 cardiologists and 290 general practitioners participated. Results: Heart failure of non-ischemic and non-hypertensive etiology which affected 10% of all patients and was particularly frequent in younger patients, both in women: &lt; 50 years old 42%; 50–65 years old 12%; &gt; 65 years old 7%; and men: &lt; 50 years old 47%; 50–65 years old 10%; &gt; 65 years old 5%; p &lt; 0.0001. Patients with non-ischemic and non-hypertensive HF were characterized by younger age, fewer co-morbidities, shorter duration of HF and, surprisingly, more advanced HF. Patients in this group were less likely to have received life-prolonging treatment in HF recommended by European Society of Cardiology (ESC) and more often required symptomatic management. Similarly, they were more likely to have implanted CRT-D and ICD. Conclusions: Heart failure of non-ischemic and non-hypertensive origin affects particularly young patients. These patients, despite suffering from more advanced HF are not optimally managed according to ESC guidelines
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