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Historic buildings are complex structures in which all the composing elements work together. Studies of heritage structures after seismic events have shown that timber roof structures strongly influence the seismic response of masonry structures, being able to reduce or enhance the out-of-plane displacement of the structure. Starting from these observations, three different types of roof structures, from the eighteenth, nineteenth and twentieth centuries, were introduced in the finite-element simulation software SCIA Engineer. The roof structures were subsequently placed on the same eighteenth-century masonry building with a ground floor and two upper floors, respecting its geometric features. Simulations were performed considering successively rigid, hinged or sliding connections between the roof and the masonry structure. At the same time, the traditionally crafted joints of the roof structures were consecutively modelled as hinged, rigid and semi-rigid (determined using three different methods). Ultimately, the top horizontal displacement, inter-storey drift and damage level of the masonry structure were compared. The main aims of this study were to observe if roof structures have an influence on the seismic behaviour of masonry buildings and to determine if selected parameters suffer any changes depending on the roof structure type, the roof–wall connections and joints’ axial stiffness.

Introduction: An exercise induced stress response is commonly seen in high performance sled dogs, resulting in increased plasma cortisol. A stress induced rise of cortisol might result in increased prevalence of gastritis and gastric ulcers mediated by an increase of gastrin. Neurexan® (Nx4) is a medicinal product used for stress relief by reduction of cortisol. The aim of the study was to show that Nx4 reduces plasma cortisol and plasma gastrin in high performance sled dogs and to show tolerability of Nx4 in dogs.Material and Methods: First, a pilot study was done to validate the increase of cortisol by performance. The data from the pilot study was used for sample size estimation via an adapted power analysis as well as the identification of important variables. These were then used in the randomization procedure of the main study. Second, a prospective randomized, double blinded, placebo-controlled cohort study was conducted. The main study included 45 sled dogs, assigning 23 dogs to the Nx4 group, and 22 dogs to the placebo group, to analyze plasma cortisol and plasma gastrin at four time points: before, directly after and 30 and 120 min after performance.Results: For the main target variable, area under the curve (AUC) of plasma cortisol, a significantly lower adjusted mean value in the Nx4 group compared to the placebo group (p = 0.031) was found. Plasma gastrin was also significantly reduced in the Nx4 group 30 min after performance (p = 0.023), resulting in a significantly reduced plasma gastrin AUC in the Nx4 group compared to the placebo group (p = 0.049).Discussion: Within the limitation of the study, the results carry implications for the usefulness of Nx4 to reduce exercise induced plasma cortisol and gastrin levels. The reduction of the exercise induced stress response could help to improve the welfare of high-performance sled dogs. Since activation of the hypothalamic-pituitary-adrenal axis resulting in increased cortisol is similar for exercise induced stress and psychologic stress, the same might be true independent of the stressor, making Nx4 potentially useful in any stressful situation for dogs.

It is generally acknowledged that heritage buildings were built by taking their environment into consideration, and therefore they have a high resilience towards various climatic factors. The increasing negative effect of the climate change on the state of conservation of valuable heritage buildings has already been recognized by heritage protection organizations, such as: The United Nations Educational, Scientific and Cultural Organization (UNESCO), The International Council on Monuments and Sites (ICOMOS), as well as by the climate change related organizations, such as: The Intergovernmental Panel on Climate Change (IPCC). The recent extreme events, which took place in the western part of Romania, reinforced the importance of the study of the effect of the climate change on the state of conservation of the built heritage. On the 17th of September 2017, a severe wind, with peak wind velocities exceeding 122 km/h (33.8 m/s) affected the heritage structures of the historic city, Timisoara. In this area, most of the city and of the nearby villages, buildings date back from the 18th century. Among the most affected buildings by the storm were the 19th century village churches. The high wind velocities mainly led to the failure of the superior part of the church towers, i.e.: belfry, spire, main roof structure. The paper aims to analyze the failure mechanisms of the towers and of the roof structures of the historic churches, from this part of Romania, affected by the high wind velocities of this particular storm.

Historic timber roof structures represent some of the most complex structural solutions of Europe’s history. They were built, until the early 19th century, in a close connection with their surround...

Historic buildings have a high resilience in time due to the fact that they were designed by taking into consideration the environment and all the local conditions. However, nowadays not only their environment is changing fast. According to a current climatic change analysis, the climate all over the world has already suffered a severe change and, unfortunately, future scenarios indicate an even worse situation. The main effects of the climate change are as follows: high and long lasting temperatures during summer, precipitation pattern change, intensification of the local winds. To which we can add more intense or even frequent extreme events, such as: drought, abundant precipitation, snowfalls and hailstorms. All these changes have a heavily impact not only on the historic buildings, but also on the economy and society. The main purpose of this study to analyse the climatic change on different types of historic buildings, the way in which natural factors increase the degradation and the failure of the building structures/historic architectural details and how it can affect the aesthetics of the historic urban centres. The subject of the research was a small town in Romania, Oravita, which was chosen due to its diversity of its historical heritage and its special climatic condition. The study focused on simple buildings as well as on archaeological sites, railroads, bridges and dams.

Timisoara is a growing city in the western part of Romania, in a seismic area, with a lot of masonry buildings with historical and cultural value, with interesting structural elements such as vaults, arches, slabs, walls, that were affected by earthquakes, subsidence of foundations, negative human actions or lack of interventions. Masonry historical structures in Banat seismic area present particular failure mechanisms, so there is a need for new, modern, fast, easy-to-apply and reversible consolidation methods. With this type of methods is possible to assure the local and global resistance, ductility, stability and rigidity for historical buildings. This article shows the consolidation methods that were applied on the buildings Sf. Gheorghe 3 and 4, in the historical centre of Timisoara, on masonry structures with historical value. The solutions that were applied are using new, innovative fibre-reinforced composite materials, in order to repair the existing damages and prevent further ones. The consolidation solutions with these new composite materials reduce the buildings vulnerability and present the advantage of being fast and easy to be executed.

Background Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma. Materials and Methods We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1. Results Activated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank-order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti-neoplastic effects were obtained by combining pimozide with KIT-targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI-1 cells. Conclusion The JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma.

Aside from clinical endpoints like height gain, health-related quality of life has also become an important outcome indicator in the medical field. However, the data on short stature and health-related quality of life is inconsistent. Therefore, we examined changes in health-related quality of life in German children with idiopathic growth hormone deficiency or children born small for gestational age before and after 12 months of human growth hormone treatment. Children with idiopathic short stature without treatment served as a comparison group. At baseline, health-related quality of life data of 154 patients with idiopathic growth hormone deficiency (n = 65), born small for gestational age (n = 58), and idiopathic short stature (n = 31) and one parent each was collected. Of these, 130 completed health-related quality of life assessments after 1-year of human growth hormone treatment. Outcome measures included the Quality of Life in Short Stature Youth questionnaire, as well as clinical and sociodemographic data. Our results showed that the physical, social, and emotional health-related quality of life of children treated with human growth hormone significantly increased, while untreated patients with idiopathic short stature reported a decrease in these domains. Along with this, a statistically significant increase in height in the treated group can be observed, while the slight increase in the untreated group was not significant. In conclusion, the results showed that human growth hormone treatment may have a positive effect not only on height but also in improving patient-reported health-related quality of life of children with idiopathic growth hormone deficiency and children born small for gestational age.

While working on rehabilitating buildings we run across structural masonry columns that carry very little bending strength and have a limited compression capacity. These columns are frequently placed between window openings. The possibility of traditionally strengthening them with reinforced concrete or steel elements risks to alter their geometry, their capacity on sustaining moisture transfer and alter their thermal insulating characteristics possibly leading to other problems caused by condensation. On new buildings that use contemporary masonry elements and have monolithic walls we come across the situation of having column like masonry elements between two windows. These elements are typically not load bearing but must resist wind pressure and dynamic horizontal loads from earthquakes while limiting thermal bridging between external and internal surfaces. This paper explores solutions for strengthening the masonry columns mentioned above using fiber reinforced mortar (FRM) and textile reinforced mortar (TRM). It also explores if there are advantages in combining the two solutions in order to limit crack development while gaining load bearing and flexural strength. The relative small thickness of the mortar on the surface provides the opportunity to limit the heat transfer and keep the external appearance of the masonry columns in comparison to using much thicker concrete strengthening solutions. For the historic buildings, the use of compatible lime based mortars as a matrix for fibers and textile mesh is explored. This would limit the potential damage that could be done by using cement mortars that seal the traditional mortar masonry and would achieve more structural strength.

Chronic myelomonocytic leukemia (CMML) is a myeloid neoplasm characterized by dysplasia, abnormal production and accumulation of monocytic cells and an elevated risk of transforming into acute leukemia. Over the past two decades, our knowledge about the pathogenesis and molecular mechanisms in CMML has increased substantially. In parallel, better diagnostic criteria and therapeutic strategies have been developed. However, many questions remain regarding prognostication and optimal therapy. In addition, there is a need to define potential pre-phases of CMML and special CMML variants, and to separate these entities from each other and from conditions mimicking CMML. To address these unmet needs, an international consensus group met in a Working Conference in August 2018 and discussed open questions and issues around CMML, its variants, and pre-CMML conditions. The outcomes of this meeting are summarized herein and include diag nostic criteria and a proposed classification of pre-CMML conditions as well as refined minimal diagnostic criteria for classical CMML and special CMML variants, including oligomonocytic CMML and CMML associated with systemic mastocytosis. Moreover, we propose diagnostic standards and tools to distinguish between ‘normal’, pre-CMML and CMML entities. These criteria and standards should facilitate diagnostic and prognostic evaluations in daily practice and clinical studies in applied hematology., This study was supported by Austrian Science Fund (FWF) grants F4701-B20 and F4704-B20, the Ludwig Boltzmann Institute for Hematology and Oncology (LBI HO) and a Stem Cell Research grant from the Medical University of Vienna.

The structural analysis of a complex roofing system – the early XX-th century Stock Exchange in Timisoara – has brought forward a paradoxical situation: this early modern building displayed an amazing collage of various traditional typologies of timber roofing, connected in order to produce a spectacular aesthetic effect of roof line. Further studies of XVIII-th, XIX-th and early XX-th century roofing structures presented an interesting evolution: until mid XIX-th century the roofs were produced by craft guilds, influenced not only by their practical knowledge but also by symbolic and traditional knowledge manifested in the choice of peculiar geometric traces (sacred geometries) not unlike the famous Chinese roofing principles, described in “Yingzao Fashi” manual. Starting with the end of the XIX-th century, the guild system vanished along with the symbolic and traditional meanings, leaving the practical knowledge completely independent – ready to be used for spectacular and aesthetic purposes (as in Art Nouveau and Secession buildings). Well into the XX-th century, even that knowledge vanished, leaving a simplified, standardized and efficient form of roof framing. Paradoxically, well into the mid XX-th century, an unconventional thinker, Buckminster Fuller, was able to generate a new kind of “roofing system”, the “geodesic dome” and the space frame structure, taking inspiration from the same kind of holistic and universal approach which animated the old craftsmen. Our investigations highlighted the overwhelming importance of a holistic and symbolic world view (“weltanschaung”) in the making of such specialized structures as the roofing frames, at least until the mid XIX-th century. A complex assessment of such structures must take into consideration these elements in order to fully understand and properly conserve and restore them for the benefit of further generations.

Chronic myeloid leukemia (CML) is a hematopoietic stem cell neoplasm in which BCR-ABL1 acts as a major driver of proliferation, differentiation and survival of leukemic cells. In a majority of all patients, leukemic cells can be kept under control by BCR-ABL1 tyrosine kinase inhibitors (TKI). Nevertheless, resistance against one or more TKI may occur. Therefore, research is focusing on novel potential drug targets in CML. We have recently identified the epigenetic reader bromodomain-containing protein 4 (BRD4) as a new therapeutic target in leukemic stem cells (LSC) in acute myeloid leukemia. In the present study, we examine the expression of BRD4 and its downstream effector MYC in CML cells and asked whether BRD4 serves as a drug target in CML cells and whether BRD4-targeting drugs, including JQ1 and newly developed BRD4 degraders (dBET1 and dBET6) are able to overcome LSC resistance in CML. Primary CML cells were obtained from 22 patients with chronic phase (CP) CML and 3 with blast phase (BP) CML. As determined by qPCR and/or immunocytochemistry, the CML cell lines KU812 and K562 as well as primary CML cells expressed BRD4 and MYC. All three BRD4-targeting drugs (JQ1, dBET1 and dBET6) were found to decrease MYC expression in KU812 and K562 cells as assessed by Western blotting. In 3H-thymidine uptake experiments, JQ1 and dBET6 were found to inhibit the proliferation of KU812 in a dose-dependent manner (IC50, JQ1: 100-500 nM; dBET6: 50-100 nM) whereas dBET1 showed only little if any effects on growth of KU812 cells (IC50: 1-5 µM), and in K562 cells, only dBET6 was found to inhibit growth with a reasonable IC50 value (250-500 nM). Corresponding results were obtained when examining drug effects on survival of CML cell lines by Annexin-V/PI staining. All three BRD4-targeting drugs were found to inhibit proliferation of primary CP CML cells with varying IC50 values. As expected, growth-inhibitory effects of dBET6 were more pronounced (IC50: Disclosures Hoermann: Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria. Wolf:BMS: Honoraria, Research Funding; Pfizer: Honoraria; Novartis: Honoraria, Research Funding; AOP Orphan: Honoraria, Research Funding. Mayer:Amgen: Research Funding; Novartis: Research Funding. Zuber:Mirimus Inc.: Consultancy, Other: Shareholder; Boehringer Ingelheim GmbH & Co KG: Research Funding. Sperr:Novartis: Honoraria; Pfizer: Honoraria; Daiichi Sankyo: Honoraria. Valent:Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria.

We introduce a portable biochemical analysis platform for rapid field deployment of nucleic acid-based diagnostics using consumer-class quadcopter drones. This approach exploits the ability to isothermally perform the polymerase chain reaction (PCR) with a single heater, enabling the system to be operated using standard 5 V USB sources that power mobile devices (via battery, solar, or hand crank action). Time-resolved fluorescence detection and quantification is achieved using a smartphone camera and integrated image analysis app. Standard sample preparation is enabled by leveraging the drone’s motors as centrifuges via 3D printed snap-on attachments. These advancements make it possible to build a complete DNA/RNA analysis system at a cost of ∼$50 ($US). Our instrument is rugged and versatile, enabling pinpoint deployment of sophisticated diagnostics to distributed field sites. This capability is demonstrated by successful in-flight replication of Staphylococcus aureus and λ-phage DNA targets in under 20 min. The ability to perform rapid in-flight assays with smartphone connectivity eliminates delays between sample collection and analysis so that test results can be delivered in minutes, suggesting new possibilities for drone-based systems to function in broader and more sophisticated roles beyond cargo transport and imaging.

In this 12-week open-label, uncontrolled study, patients (n=85; mean [SD] age 11.2 [3.95] years) were trained to use an injection device with an automatic needle insertion accessory (NordiFlex/NordiFlex PenMate: Novo Nordisk A/S, Bagsvaerd, Denmark) for growth hormone (GH) injection. The opinions of patients and the physicians/nurses who trained patients on device were recorded by questionnaire. Most (88.4%) patients reported that the device was “very easy/easy" to use. The majority (82.4%) of patients were “very satisfied/satisfied" with the device and 64% wished to continue its use. Device training instructions were reported as “very easy/easy" by 96.1% of physicians/nurses, and 65.8% of participants could use the device after ≤10-minute training. In this study, NordiFlex PenMate was well accepted by patients and medical staff. Patients had a high opinion of the device and over half wished to continue its use. High patient acceptance may facilitate treatment adherence optimizing treatment outcomes.

The Western is typically regarded in scholarship as falling clearly and nearly exclusively into the realm of popular culture. Instantiations of Western films may achieve the cinematic version of high art, as John Ford’s Westerns are often understood to do. But, in fact, there is also an avant-garde history of/in Westerns that goes back, in one version, to Andy Warhol’s Lonesome Cowboys (1968) or, in another, to The Great Train Robbery (1903—when all cinema was still in an experimental phase). These films are outside of mainstream practice, but their concerns may not be. In an avant-garde or experimental mode, the Western’s aesthetics are allowed to expand, and the critical register of any given text can be as powerful a critique, and use, of the genre’s past (and its future) as any feature film. Here I concentrate on two key works in an experimental mode that represent important tendencies and questions in the avant-garde/Western interface: Mandy Morrison’s video work Desperado (1999), and Rebecca Baron and Douglas Gordon’s digital work Lossless #3 (2008). Mandy Morrison’s Desperado (first seen widely when it was exhibited in the Whitney Biennial of 2000) uses the medium-specific aesthetics of video art to think through masculinity and sexual identity using Western semantic codes and a destabilized version of Western narrative.

Atherosclerosis often presents as a complex systemic disease that is strongly influenced by lifestyle factors, but also by the genetic background. The sequence variant rs1333049 affects the expression of ANRIL, a noncoding RNA transcript playing a key role in the regulation of inflammatory processes. We thus aimed to replicate the predictive value of genetic information on this variant regarding the development of cardiovascular events in an Austrian high-risk cohort.Nine hundred and eighty-eight patients from an angiologic outpatient ward at a large University hospital were genotyped by means of the 5'-nuclease assay. Relative risk ratios were assessed for carriers of different alleles. Statistical independence of genetic information was evaluated in multivariable analysis including known risk markers.In patients carrying the [G]-allele, metabolic parameters (serum low-density lipoprotein, total cholesterol) significantly decreased during the initial 6 months of the observation period (P 0.01). Likewise, homozygous [C]-allele carriers were at a higher risk of suffering myocardial infarction (relative risk = 2.681, 95% confidence interval 1.418-5.070). In contrast, we found no interaction between rs1333049 genotype and progression of carotid atherosclerosis or stroke.These results are in line with the previous findings, suggesting that genetic information on the rs1333049 variant might be a useful predictor of adverse cardiac events. Thus, we could successfully replicate the predictive value of the 9p21 risk allele in an Austrian cohort.