46 research outputs found

    A Model Proposal for Store Design with Shape Grammar

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    With the widespread use of computers, rule-based design methods that can work in harmony with computer logic and can be easily adapted to the computer environment have come to the forefront in the design world. To be able to analyze the logic of a design made with the shape grammar method which is one of the rule based design methods; it is even possible to modify and transform the design, which has been placed on the rule base by removing shape rules, or to create new designs with the same design logic. In this study, some stores that will be exemplary for the store design are examined, analyzed and the system is designed to produce new plan schemes. In this study, it is aimed to produce a program that offers abstract plan alternatives to the designer during the early design process. In store design, clothing stores are emphasized especially due to its intensive use. Within the scope of the study, it is focused on developing a program that produces plan alternatives by using computational power of computer. In this way, it was possible to work on many plan alternatives in a short time during the design process and it became easy to examine large areas. With these alternatives, it is aimed to provide rapid and advance detection of possible problems that may arise. At this point, it is aimed to see a large number of plan alternatives by applying a few rules and to make the appropriate selection among these alternatives

    Global Teamwork: A Study of Design Learning in Collaborative Virtual Environments

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    With the recent developments in communication and information technologies, using Collaborative Virtual Environments (CVEs) in design activity has experienced a remarkable increase. In this paper we present a collaborative learning activity between the University of Sydney (USYD), and the Istanbul Technical University (ITU). This paper shares our teaching experience and discusses the principles of collaborative design learning in virtual environments. Followed by a study on students’ perception on the courses and collaborative learning in both universities, this paper also suggests future refinements on the course structure and the main areas of collaborative design learning. Keywords: Collaborative Design; Collaborative Virtual Environments; Design Teaching And Learning</p

    An Interaction form Generation Tool: EduDesign

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    AbstractThis paper investigates contributions of customized and simplified generative design tools on the development of novice architects‟ abilities of accelerating their interactions with digital tools and adapting new digital design processes with them. For this purpose, a plugin, called as EduDesign and including various form generations and instructional practices based basic design education, have been developed by scripts of 3D software. Its potentials tested and enriched by different student groups experiences in KBU and ITU. According to the obtained results, positive and negative influences of the plugin are evaluated

    Examination of VaR after long term capital management

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    The 1998 failure of Long-Term Capital Management (‘LTCM’), a very large and prominent Greenwich, Connecticut based hedge fund, is said to have nearly brought down the world financial system. Over the years, few financial debacles such as LTCM, have been so often written about or discussed without a firm conclusion on what went wrong. What brought the “genius” managers of LTCM to their knees? Was it hubris, or was it something more? Various commentators have jumped on LTCM’s significant leverage ratio or engaged in second-guessing of management’s decision in 1997 to return $2.7 billion of investor capital to increase leverage, and thereby, returns. Others have faulted the lack of transparency at LTCM or faulted regulators for a lack of oversight, criticized regulators for arranging the bailout, while others still have pinpointed the debacle on the failure of LTCM’s risk management prowess. This paper avoids the blame and identifies the multiple factors, both management risk management blunders, as well as inherent flaws in the risk metric used by LTCM – Value at Risk (VaR) – a commonly used risk metric in the financial industry today

    Large domains of heterochromatin direct the formation of short mitotic chromosome loops

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    During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here, we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of high levels of heterochromatic H3 lysine nine trimethylation (H3K9me3). Hi-C and microscopy indicate that the heterochromatinised fission yeast DNA is organised into smaller chromatin loops than flanking euchromatic mouse chromatin. We conclude that heterochromatin alters chromatin loop size, thus contributing to the distinct appearance of heterochromatin on mitotic chromosomes

    Glutathione monoethyl ester prevents TDP-43 pathology in motor neuronal NSC-34 cells

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    © 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (August 2017) in accordance with the publisher’s archiving policyOxidative stress is recognised as central in a range of neurological diseases including Amyotrophic lateral sclerosis (ALS), a disease characterised by fast progressing death of motor neurons in the brain and spinal cord. Cellular pathology includes cytosolic protein aggregates in motor neurons and glia of which potentially cytotoxic hyper-phosphorylated fragments of the Transactive response DNA Binding Protein 43 kDa (TDP-43) constitute a major component. This is closely associated with an additional loss of nuclear TDP-43 expression indicating a “loss of function” mechanism, accelerating motor neuron (MN) loss. Furthermore, mutations in TDP-43 cause familial ALS and ALS-like disease in animal models. In this study, we investigated the role of glutathione (GSH) in modulating oxidative stress responses in TDP-43 pathology in motor neuron NSC-34 cells. Results demonstrate that depletion of GSH produces pathology similar to that of mutant TDP-43, including occurrence of cytosolic aggregates, TDP-43 phosphorylation and nuclear clearing of endogenous TDP-43. We also demonstrate that introduction of mutant TDP-43A315T and silencing of endogenous TDP-43, but not overexpression of wild-type TDP-43, result in similar pathology, including depletion of intracellular GSH, possibly resulting from a decreased expression of a regulatory subunit of ɣ-glutamylcysteine ligase (GCLM), a rate limiting enzyme in GSH synthesis. Importantly, treatment of mutant cells with GSH monoethyl ester (GSHe) that directly increases intracellular GSH and bypasses the need for GSH synthesis, protected against mutant-induced TDP-43 pathology, including reducing aggregate formation, nuclear clearance, reactive oxygen species (ROS) production and cell death. Our data strongly suggest that oxidative stress is central to TDP-43 pathology and may result from a loss of function affecting GSH synthesis and that treatments directly aimed at restoring cellular GSH content may be beneficial in preventing cell death in TDP-43-mediated ALS

    Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients

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    Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment
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