Tudor Place

İktisadi planlamanın sektörel düzeyde en önemli analiz araçlarından birisi girdi-çıktı modelleridir. Bu analiz üzerinden, hangi sektörlere yatırım önceliğinin verilmesi gerektiği tespit edilebilmektedir. Bu çalışmada, Kırgız Cumhuriyeti için Asya Kalkınma Bankası’nın 2018 yılı verileriyle hesapladığı girdi-çıktı tablosu kullanılmıştır. Çarpan analizi ve bağlantı etkilerinin incelendiği çalışmada, kilit sektörler tanımlanmıştır. Buna göre; finansal aracılık, inşaat, taşımacılık hizmetleri ile eğitim, sağlık ve sosyal hizmet sektörleri çarpan analizinde ön plana çıkmaktadır. Öte yandan bağlantı etkilerinden elde edilen bulgulara göre; tarım, avcılık, ormancılık ve balıkçılık, ağır imalat ile finansal aracılık sektörlerinin kilit nitelikte olduğu tespit edilmiştir. Son olarak ileri ve geri bağlantı etkileri sonuçlarına göre, her iki etkinin de en yüksek olduğu sektör finansal aracılık sektörüdür.

Introduction: In the early window, time to treatment with endovascular thrombectomy (EVT) is inversely associated with favorable clinical outcomes but this remains unclear in the extended window. We aimed to assess the impact of time to EVT on clinical outcomes in the DAWN trial. Methods: The association between every 1-hour treatment delay with 90-day functional independence (modified Rankin Scale [mRS] 0-2), symptomatic intracranial hemorrhage (SICH), and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs witnessed vs unwitnessed) considering both time from last seen well (TLSW) and time from symptoms first observed (TSFO). Results: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6-12-hour and 12-24-hour time window, respectively. Considering all three modes of onset together, there was no statistically significant association between TLSW to randomization with either functional independence or mortality at 90 days in either the EVT (mRS0-2 OR 1-hour-delay:1.07;95%CI[0.93-1.24]; mRS6 OR:0.84;95%CI[0.65-1.03]) or medical management (mRS0-2 OR1-hour-delay:0.98;95%CI[0.80-1.14]; mRS6 OR 1-hour-delay:0.94;95%CI[0.79-1.09]) groups. Moreover, there was no significant interaction between treatment effect and time (p=0.439 and p=0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between TLSW to successful reperfusion (mTICI≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p=0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p=0.018) negative slope in wake-up patients. There was no association between treatment times and SICH. Comparable analysis using TSFO yielded similar results. Conclusion: In extended window patients, the association between time to treatment and clinical outcomes seems to be primarily driven by successfully perfused patients with wake-up rather than witnessed or unwitnessed strokes suggesting that wake-up strokes do not behave as “slow-progressors”.

We present a novel, deep-learning based method -- dubbed Galactic-Seismology Substructures and Streams Hunter, or GS$^{3}$ Hunter for short, to search for substructures and streams in stellar kinematics data. GS$^{3}$ Hunter relies on a combined application of Siamese Neural Networks to transform the phase space information and the K-means algorithm for the clustering. As a validation test, we apply GS$^{3}$ Hunter to a subset of the Feedback in Realistic Environments (FIRE) cosmological simulations. The stellar streams and substructures thus identified are in good agreement with corresponding results reported earlier by the FIRE team. In the same vein, we apply our method to a subset of local halo stars from the Gaia Early Data Release 3 and GALAH DR3 datasets, and recover several, previously known dynamical groups, such as Thamnos 1+2, Hot Thick Disk, ED-1, L-RL3, Helmi 1+2, and Gaia-Sausage-Enceladus, Sequoia, VRM, Cronus, Nereus. Finally, we apply our method without fine-tuning to a subset of K-giant stars located in the inner halo region, obtained from the LAMOST Data Release 5 (DR5) dataset. We recover three, previously known structures (Sagittarius, Hercules-Aquila Cloud, and the Virgo Overdensity), but we also discover a number of new substructures. We anticipate that GS$^{3}$ Hunter will become a useful tool for the community dedicated to the search of stellar streams and structures in the Milky Way (MW) and the Local group, thus helping advance our understanding of the stellar inner and outer halos, and of the assembly and tidal stripping history in and around the MW.

The article analyzes the representation of the cities of Bologna, Limoges and Thessaloniki, in the contemporary Italian, French and Greek noir novel (1995-2015), from a geocritical perspective.The reflection develops in two stages.In the first stage, the three cities are presented as places of crime to be deciphered, on the basis of five characteristics: dilation, dehumanization, disorientation, deculturation, deindividuation.In the second stage, we try to define the challenge of contemporary detectives: to read cities, as codes to be deciphered, to solve crimes.Our interpretation of the city in contemporary noir fiction develops in five phases, mirroring the characteristics of the first part: exploration, detection, reconstruction, identification, acceptance.At the end of his investigation and the novel, the detective discovers that the city is a real character, it is not only a place of crime but also a place of the soul, a mirror of the experiences of the protagonists.The contemporary noir novels of Bologna, Limoges and Thessaloniki depict the conflict, perhaps insoluble, which revolves around the definition of what is the city and therefore who is the man and they indicate the impossibility of a definitive and reassuring answer.The man and the city merge to become one.

Abstract Background: Glucose and glutamine are major carbon and energy sources that promote the fast proliferation of cancer cells. The Warburg effect, characterized by shifted flux ratio between aerobic and anaerobic respirations, is considered as a common metabolic reprogramming mechanism in cancer. The further discovery of glutaminolysis pathway elucidated the role of glutamate in providing energy and carbon source in cancer metabolism. Variations in the branches of the central metabolism of glucose and glutamate have also been observed. However, most of these observations were made on cell line or mouse systems, which cannot mimic the dysbalanced nutrient, redox, pH and oxygen levels in a real tumor microenvironment (TME), which may heavily shift in a TME and determines the metabolic phenotypes of a cancer. Analysis: In this study, we conducted a systematic evaluation of the metabolic reprogramming and characteristics via a computational analysis by using pan-cancer transcriptomics data of 11 cancer subtypes and 9 matched adjacent normal tissue types. We focused on the flux distribution and variations of the central energy metabolism and its key branches. We first reconstructed the central metabolism pathway in a subcellular resolution by including glycolytic pathway, production of lactate, TCA cycle, nucleic acids synthesis, glutaminolysis, glutaminate, glutamine and glutathione metabolism, and other amino acids synthesis. We applied our in-house developed scFEA method on TCGA pan-cancer transcriptomics data. Results: Our analysis confirms the increased influx in glucose uptake and glycolysis and decreased upper part of TCA cycle, i.e., Warburg effect in almost all the analyzed cancer types. However, increased lactate production and the second half of TCA cycle were only seen in certain cancer types. More interestingly, we did not see cancer tissues have highly shifted glutaminolysis compared to their adjacent normal tissues. A systems biology model of metabolic shifts through cancer and tissue types is further developed and analyzed. We observed that (1) normal tissues have distinct metabolic phenotypes, (2) cancer types have drastically different metabolic shifts compared to their adjacent normal controls, and (3) the different shifts happened to tissue specific metabolic phenotypes result in a converged metabolic phenotype through cancer types and cancer progression. This study strongly suggests the possibility to have a unified framework for studies of cancer-inducing stressors, adaptive metabolic reprogramming, and cancerous behaviors. Citation Format: Alex Lu, Haiqi Zhu, Kevin Hu, Grace Yang, Shaoyang Huang, Pengtao Dang, Sha Cao, Chi Zhang. Flux estimation analysis systematically characterizes the metabolic shifts of the central metabolism pathway in human cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2047.

ralise avec les bases de donnes des journaux en ligne, respectivement Yomidasu Rekishikan et Kikuz Bijuaru .

Protein kinases are important targets for study due they act as direct regulators of the cell cycle. The progression of the cell division cycle is driven by cyclins, which bind and activate their catalytic partners, cyclin-dependent kinases (CDKs). CDKs comprise a family of proteins that can be subdivided into two major functional groups based on their function in the cell cycle and / or transcriptional control. The CDK-cyclin specific heterodimeric complexes phosphorylate several cellular proteins, which promote entry into the cell cycle, regulation of DNA synthesis and segregation of newly duplicated chromosomes during mitosis. Cyclin D3 has the function of acting in phase G1 as a regulatory subunit of CDK4 and CDK6, and also as a partner of CDK11p 58 in phase G2 / M during the progression of the cell cycle. Overexpression of cyclin D3 correlates with increased cell proliferation and tumor growth, in addition to being able to inhibit the androgen receptor transactivation activity. The aim of the present study is to overexpress cyclin D3 using the bacterial expression system (Escherichia coli) in order to obtain the purified protein with adequate purity for structural characterization and kinase activity of the CDK11-cyclinD3 complex. The use of different vectors types allowed obtaining the interest protein of through a refolding process and in a native way. The results obtained for the expression in both vectors, produced proteins with more than 95% of purity. The result of the circular dichroism (CD) spectroscopy characterization assays of the cyclin D3 protein in the native (soluble) form showed a very similar pattern of secondary structures per CD when compared to the result of the refolded protein, with about 39% of helices and 15% -strands. By fluorescence emission spectroscopy, it was shown that the protein is stable against the chaotropic agent urea, but unstable in the presence of increasing concentrations of guanidine chloride. The kinase activity assay of the CDK11-cyclinD3 complex allowed to ensure the correct conformation of the recombinant proteins obtained in both vectors. These data validate the refolding protocol, serving as a basis for future studies involving the production of recombinant proteins and for studies involving possible inhibitors for this complex.