562 research outputs found

    Development of Real Estate Market in the Czech Republic

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    The article deals with analysis of the current situation on the real estate market in the Czech Republic. Software EVAL, which continually collects, examines and evaluates advertised quotations of real estates, was used for mapping and evaluation of the real estate market development. The article provides professional public with detailed view on the time progress of quotations and tenancy of flat units in dependence on the significant parameters of properties and a locality.

    On mechanics of deformation and crushing processes

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    The mechanics of crushing and breaking of particles is one of the most intractable problems in materials science. The stressed states of processed materials are significantly inhomogeneous, and thus the deformation and disintegration mechanisms vary greatly. Two techniques have been developed for realizing these processes as a quasi-homogeneous transition. The device and method developed by Enikolopov transform a solid polymer spontaneously into powder. The same loading system is now used for obtaining fine-grained metals, similarly as when using the ECAP device developed by Valiev. Both techniques are now used for obtaining nanostructured materials. The common feature of both types of methods is the formation of new physical surfaces. These are particle-free oversurfaces or grain boundaries. The method requires a supply of energy in the form of mechanical work, and this is mostly done by simultaneous action of pressure and shear stress. The formation offree oversurfaces in stressed solid bodies is the subject offracture mechanics. The Griffith equation is employed to describe the problem.Механика дробления и разрушения частиц является одной из трудноразрешимых проблем материаловедения. Напряженное состояние обработанных материалов значительно неоднородно, и поэтому механизмы деформирования и разрушения существенно отличаются. Разработаны два метода для реализации этих процессов как квазиоднородного перехода. С помощью устройства и метода, разработанных Ениколоповым, твердый полимер самопроизвольно преобразуется в порошок. Аналогичная система нагружения используется для получения мелкозернистых металлов, подобно использованию устройства для равноканального углового прессования, разработанного Валиевым. Оба метода используются в настоящее время для получения наноструктурных материалов. Образование новых физических поверхностей является общей чертой обоих методов. Они представляют собой свободные от частиц верхние поверхности, над- поверхности или границы зерен. В соответствии с методом Валиева, требуется подача энергии в виде механической работы, что обычно осуществляется одновременным воздействием давления и касательного напряжения. Поскольку образование свободных надповерхностей в нагруженных твердых телах является предметом механики разрушения, для решения этой задачи используется уравнение Гриффитса

    Update on the Treatment of Diabetic Retinopathy

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    Retinopathy is the most feared complication of diabetes, compromising quality of life in most sufferers. Almost all patients with type 1 diabetes will develop retinopathy over a 15- to 20-year period, and approximately 20–30% will advance to the blinding stage of the disease[1]. Greater than 60% of patients with type 2 diabetes will have retinopathy. This situation is highlighted by the frightening statistic that diabetic retinopathy (DR) remains the most common cause of vision impairment in people of working age in Western society. With the global epidemic of type 2 diabetes, this predicament is set to worsen as over 360 million people are projected to suffer from diabetes and its complications by 2030. Vision loss from diabetes is due to a number of factors, including haemorrhage from new and poorly formed blood vessels, retinal detachment due to contraction of deposited fibrous tissue, and neovascular glaucoma resulting in an increase in intraocular pressure. Diabetic macular oedema is now the principal cause of vision loss in diabetes and involves leakage from a disrupted blood-retinal barrier. In terms of treatment, there is clear evidence that strict metabolic and blood pressure control can lower the risk of developing DR and reduce disease progression. Laser photocoagulation and vitrectomy are effective in preventing severe vision loss in DR, particularly in the most advanced stages of the disease. However, both procedures have limitations. This review examines evidence from preclinical and clinical studies that shows that targeting inhibition of the renin-angiotensin system, vascular endothelial growth factor, corticosteroids, protein kinase C, growth hormone, and advanced glycation end-products are potential treatments for DR

    Retinal dysfunction in diabetic Ren-2 rats is ameliorated by treatment with valsartan but not atenolol

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    PURPOSE. To determine whether diabetes leads to retinal neuronal dysfunction in hypertensive transgenic (mRen-2)27 rats (Ren-2), and whether the effect can be prevented by treatment of hypertension with either the angiotensin-1 receptor blocker (AT1-RB) valsartan or the ␤1-adrenergic receptor antagonist atenolol. METHODS. Six-week-old Ren-2 rats were made diabetic (streptozotocin 55 mg/kg; n ϭ 34) or remained nondiabetic (0.1 M citrate buffer; n ϭ 43) and studied for 20 weeks. A subset of animals received valsartan (4 mg/kg per day) or atenolol (30 mg/kg per day) by gavage. Sprague-Dawley (SD) rats served as normotensive controls for blood pressure (BP). We evaluated retinal function in all groups with a paired-flash electroretinogram over high light intensities (0.5-2.0 log cd-s ⅐ m Ϫ2 ), to isolate rod and cone responses. RESULTS. A reduction in amplitude of all electroretinogram components (PIII, PII, OPs, cone PII) was found in nondiabetic Ren-2 compared with nondiabetic SD rats. A further reduction was observed in diabetic Ren-2 rats. Treatment of both nondiabetic and diabetic Ren-2 rats with valsartan or atenolol reduced BP to within normal limits. This reduction produced some improvement in function in treated nondiabetic Ren-2 rats. However, in treated diabetic Ren-2 rats, retinal dysfunction was ameliorated by valsartan but not by atenolol, with a significant improvement (P Ͻ 0.05) observed in all components of the electroretinogram, with the exception of the OPs. CONCLUSIONS. These findings suggest that hypertension induces retinal dysfunction that is exacerbated with diabetes and ameliorated by treatment with an AT1-RB, and not just by normalizing BP. These data provide further evidence for the importance of the renin-angiotensin system in development of diabetic complications. (Invest Ophthalmol Vis Sci. 2007;48: 927-934

    NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy

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    <b>Aims:</b> Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. <b>Results:</b> Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. <b>Innovation:</b> Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. <b>Conclusions:</b> Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathie

    Advanced cryo-tomography workflow developments - correlative microscopy, milling automation and cryo-lift-out

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    Cryo-electron tomography (cryo-ET) is a groundbreaking technology for 3D visualisation and analysis of biomolecules in the context of cellular structures. It allows structural investigations of single proteins as well as their spatial arrangements within the cell. Cryo-tomograms provide a snapshot of the complex, heterogeneous and transient subcellular environment. Due to the excellent structure preservation in amorphous ice, it is possible to study interactions and spatial relationships of proteins in their native state without interference caused by chemical fixatives or contrasting agents. With the introduction of focused ion beam (FIB) technology, the preparation of cellular samples for electron tomography has become much easier and faster. The latest generation of integrated FIB and scanning electron microscopy (SEM) instruments (dual beam microscopes), specifically designed for cryo-applications, provides advances in automation, imaging and the preparation of high-pressure frozen bulk samples using cryo-lift-out technology. In addition, correlative cryo-fluorescence microscopy provides cellular targeting information through integrated software and hardware interfaces. The rapid advances, based on the combination of correlative cryo-microscopy, cryo-FIB and cryo-ET, have already led to a wealth of new insights into cellular processes and provided new 3D image data of the cell. Here we introduce our recent developments within the cryo-tomography workflow, and we discuss the challenges that lie ahead. Lay Description This article describes our recent developments for the cryo-electron tomography (cryo-ET) workflow. Cryo-ET offers superior structural preservation and provides 3D snapshots of the interior of vitrified cells at molecular resolution. Before a cellular sample can be imaged by cryo-ET, it must be made accessible for transmission electron microscopy. This is achieved by preparing a 200-300 nm thin cryo-lamella from the cellular sample using a cryo-focused ion beam (cryo-FIB) microscope. Cryo-correlative light and electron microscopy (cryo-CLEM) is used within the workflow to guide the cryo-lamella preparation to the cellular areas of interest. We cover a basic introduction of the cryo-ET workflow and show new developments for cryo-CLEM, which facilitate the connection between the cryo-light microscope and the cryo-FIB. Next, we present our progress in cryo-FIB software automation to streamline cryo-lamella preparation. In the final section we demonstrate how the cryo-FIB can be used for 3D imaging and how bulk-frozen cellular samples (obtained by high-pressure freezing) can be processed using the newly developed cryo-lift-out technology

    A comparative analysis of the costs of onshore wind energy : Is there a case for community-specific policy support?

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    Acknowledgements and Funding sources: This work has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement No. 316020; and also from the Scotland’s Centre of Expertise on Climate Change (‘ClimateXChange’). We thank Vijay Bhopal and Sandy Robinson for their invaluable contribution to the original report and the Editor and anonymous reviewers for their comments on the original draft paper.Peer reviewedPostprin

    Candesartan Attenuates Diabetic Retinal Vascular Pathology by Restoring Glyoxalase-I Function

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    This is an uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association, publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online a
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