A comparative analysis of the interrelation between the evolution in the structure of Armenian churches of the 4th-14th centuries and the three-layer “midis” masonry

The article touches upon the interrelations between the structural elements and the building structure in architecture. The aim of the work is to generalize the peculiarities of “midis” masonry formation and to reveal its influence in the evolution process of the structure of Armenian medieval churches by a comparative analysis of different characteristics. In the work: the development of three-layer “midis” masonry was systematized, the phenomenon of shell structure and spatial integrity in the churches of the 4th-14th centuries was highlighted, the tendencies of evolution of the masonry monolithic nature and church structure integrity were revealed by a comparative analysis of volumetric and planning characteristics of different churches. The results allowed to formulate a certain sequence of interactions in different characteristics, which confirmed the relationship between the evolution of the masonry and the structure of the churches: the evolution of “midis” masonry led to the structural monolithic nature of the walls and the forms derived from it, which in turn led to the integrity of the stone building structure. The results can be useful in further research covering structural-compositional interrelations, including both heritage and modern architecture studies

Mechanisms acting on Hedgehog-GLI pathway and their therapeutic potential

Hedgehog signaling is crucial for diverse aspects of animal development, essential in regulating many cellular processes and is largely implicated in various forms of human cancer. However, many aspects of Hedgehog signaling are not completely understood. This thesis aims to contribute towards a better understanding of the mechanisms acting on Hedgehog-GLI signaling and explore their possible therapeutic potential. PAPER I. We demonstrate that the small molecule RITA, a p53 activator, downregulates Hedgehog signaling in human medulloblastoma and rhabdomyosarcoma cells via JNK kinase and irrespective of p53. In vitro RITA enhanced the anti-proliferative effects of the GLI antagonist GANT61. RITA was more potent than GANT61 in downregulating Hedgehog-GLI signaling in rhabdomyosarcoma subcutaneous xenograft tumors with the dual drug administration almost completely blocking the Hedgehog signaling response in vivo, suggesting a certain antagonism of the two drugs. Notably, RITA and GANT61 co-administration decreased cell proliferation and elicited a broader response of pathways involved in cancer cell growth, providing a plausible interpretation for tumor reduction in the absence of Hedgehog signaling downregulation. PAPER II. We address the possible therapeutic role of Hedgehog-GLI1 signaling for targeting and prognosis of ER-alpha positive breast cancer. We showed that expression of the Hedgehog signaling effector protein GLI1 is higher in tamoxifen resistant relative to tamoxifen sensitive cells. In both cell types GLI1 depletion mitigated cell proliferation and ER-alpha activity, irrespective of estrogen stimulation. Tamoxifen cytotoxicity was enhanced by GANT61 co-treatment, both in tamoxifen resistant and sensitive breast cancer cells, reflecting a crosstalk between ER-alpha and Hedgehog-GLI1 signaling. We have observed a positive correlation between GLI1 and ER-alpha/ER-alpha target gene expression, while high GLI1 expression was associated with poor distant metastasis-free survival in breast cancer patients. PAPER III. We identified a signature of GLI1 target genes via a combination of RNA-seq analyses of GLI1 overexpression and depletion datasets supplemented with in-depth validation in human cancer cell lines. Additionally, we found that RNA editing of GLI1 can modulate its effects on GLI1 target genes. Markedly, one of the highly upregulated targets, FOXS1, was found to engage in feedback mechanisms limiting the capacity of GLI1 to act as a proliferation factor in medulloblastoma and rhabdomyosarcoma cells. FOXS1 was both highly expressed and positively correlated with GLI1 in SHH medulloblastoma, further arguing for the existence of a FOXS1-GLI1 interplay in human tumors. PAPER IV (Manuscript). In this ongoing work we address the role of circRNAs in the context of Hedgehog signaling activation and Hedgehog-linked SHH medulloblastoma tumors. Via modified RNA-seq protocols we have determined the circRNA transcriptome of Daoy medulloblastoma and human embryonic palatal mesenchyme HEPM cells, following activation of Hedgehog pathway with SHH ligand or Smoothened agonist SAG. In total, 29 selected circRNAs were independently validated by Sanger sequencing and RT-PCR assays. Of these circRNAs, 10 were apparently regulated by Hedgehog signaling activation, however to a much lesser extent compared with known target genes of the pathway, e.g. GLI1 and HHIP. 7 circRNAs had reduced expression in human medulloblastoma tumors in comparison to normal cerebellum, while the linear mRNAs originating from the same genes did not exhibit a reduced expression. These findings highlight distinct regulatory mechanisms acting on the BACH1, CDYL, FKBP8, GLIS1, OGDH, SMARCA5 and ZKSCAN1 circRNAs and deserve further analysis for possible contribution to the development of medulloblastoma

On the Transformation of Petri Nets into BPMN Models

Antud magistritöö käsitleb Petri võrkude teisendamist samaväärseteksBPMN mudeliteks. Täpsemalt öeldes keskendub see Petri võrkude alamklassilenimega töövoo võrgud. Antud lõputöös implementeeriti teisendaja, kasutadesselleks mitmeid tehnikaid nagu näiteks Petri võrkude lahti pakkimineja modulaarsed dekompositsiooni puud. Sellest tulenevalt pakub antud magistritöö välja täieliku teisendusalgoritmi, mis suudab käsitleda sümmeetrilisi segadusi Petri võrkudes. See on antud valdkonnas üks esimesi teisendamise meetodeid, mis katab ka seda klassi. Hetkel oleme teadlikud ainult ühest teosest, mis illustreerib mõlemasuunalist teisendamist töövoo võrkude ja graafide vahel. Lisaks, esitleme me käitumissõltuvuste maatriksi arvutamise meetodi.Käsitleme ka erijuhtumeid, kus peame BPMN-is lisama tau sündmuse, ettegemist oleks samakujulise mudeliga.This thesis addresses the problem of translating a Petri net into an equivalentBPMN process model. This is fundamental problem with implications on theunderstanding of the semantics of the notation and that has potential applications in areas such process model discovery from event logs and structuring of process models. In previous work, it has been shown that the well-known family of free-choice Petri nets can be bidirectionally mapped into the subset of BPMN process models constructed solely with tasks and exclusive/parallel getaways. In contrast, this work searches at lifting the restriction to a larger family of Petri nets by proposing a translation that covers also the case of nets with symmetric confusion. The approach has been implemented in a prototype which has allowed us to conduct a preliminary performance study

THE REAL AND THE FABRICATED IN THE SCREENPLAY “THE STATION OF FOSSIL MAN”

My PhD project consists of a screenplay and exegesis. The exegesis examines the issues of marriage and sexuality that are explored in the screenplay as subjects of disagreement between the old and new generations of intelligentsia in post-Soviet Armenia. This paper presents those sections from the exegesis, which investigate how this historical moment is reflected in my screenplay in terms of verisimilitude. I claim the representation of the Armenian intelligentsia in my screenplay is in the spirit of “authentic realism”. Reflecting on the real and the imagined in the narrative of my screenplay, I argue that there is “critical information,” directly based on the actual, that helps a writer create realistic fiction. I put forth a theory that the narrative discourse in my screenplay consists of two levels – fundamental and fictive, the former representing the real in the narrative, while the latter – the imagined. Using this theory I suggest that the degradation of the Armenian intelligentsia embodied by the protagonist in the screenplay captures realistically the actual cultural moment in post-Soviet Armenia.&nbsp

The reflection of the urban environment in the hagiographic works of the 6th–8th cc. AD.

The main objective of the article is to present a picture of the early medieval city through hagiographic works. The article presents the places (prison, squares) associated with the activities of the saints. These places in the urban environment are mentioned in connection with the torture and murder of saints, which conveys them a special meaning. It was the hagiographic literature that reflected the gradual decline in the role of the prison in the Middle Ages, where the punishment is served in a form hidden from the eyes of the inhabitants, and the strengthening of the role of the execution place, where the punishment is carried out publicly and in especially cruel forms, with the aim of intimidating and suppressing the audience, binding the active and passive participants in this action with mutual responsibility. In the early Middle Ages, ideas about death changed, the dead, as it were, settled in the city of the living. Certainly, first of all, it is about the grand martyrs, the saints tortured to death became the heavenly patrons of the city. At that, in the Armenian and Georgian hagiography, not only the relics of the saints were sacralized, but also the places of their execution. Hagiographic principles of this particular project about the internal environment of cities Connected by a chain wall. In the center of early-century Armenia, located in the Dvina, in its Central Square, the beginning of the VI century. the social environment of the creation of people arose. Here, after the revival of the palace of the Persian Amarkar, in all likelihood, there was a lack of freedom in the Constitutional Rule of individual situations. The best example of cooperation was the fire that broke out in the aforementioned palace of the Persian Аmarkar, when the Armenians, according to a preliminary agreement, rushed to help

The Activities and Limits of the Médecins Sans Frontières in North Korea During the 1990s

학위논문 (석사) -- 서울대학교 대학원 : 국제대학원 국제학과(한국학전공), 2021. 2. 박태균.NGOs are one of the few ways to reach out to North Koreans that are locked in their own country as there is no direct communication with the international society. Humanitarian NGOs started their activities in North Korea in the 1990s when for the first time in its history the North Korean government asked for humanitarian aid. However, despite the presence of many different humanitarian agencies in North Korea since the 1990s healthcare violations remain to be unsolved. Due to unequal and insufficient healthcare throughout the whole country, the weakest parts of the population are suffering from diseases that are curable in other parts of the world. Médecins Sans Frontières was one of the first NGOs to enter North Korea, but eventually, after facing numerous challenges and difficulties it had to withdraw from North Korea. This research is focused on international humanitarian NGOs role and their limitations in exposing the importance of the right to health and raising awareness about the chaotic situation of healthcare in North Korea. Our analysis through the case study of Médecins Sans Frontières aims at getting an answer to the question of what kind of operational and institutional issues NGOs encountered during 1995-1998 while advocating basic human rights.건강권은 유엔 헌장의 채택으로 1945년 처음 시작된 이래 유엔 활동의 중심축이었지만 많은 국가들에서 건강권은 여러 가지 요인으로 인해 침해당하고 있다. 인도주의적 NGO는 인권 상황이 열악한 국가에서 건강에 관한 관리를 옹호하는 데 중요한 역할을 한다. 1990년대부터 북한에서 활동 중인 NGO도 인권 상황을 개선하기 위해 노력해 왔지만 인권 침해 측면에서 보면 북한은 세계에서 가장 위급한 나라 중 하나로 꼽힌다. 북한은 다른 국가와 비교하면 경제적·정치적으로 특별한 현실이라서 북한에서 활동하는 NGO의 목적도 전략도 매우 다르다. 본 연구는 북한 정부가 처음으로 인도적 지원을 요청한 후 북한에서 활동을 시작한 국경없는 의사회(MSF)의 사례에 초점을 맞추었다. MSF 사례를 통해 본 연구는 1990년대 중반 북한에서 국제 NGO가 지속 가능한 인도주의적 활동 한계의 주요 원인이 무엇인지를 지적하는 것을 목표로 하고 있다. MSF는 북한에 들어온 최초의 NGO 중 하나이지만 다양한 도전과 어려움에 직면했고 1990년대 후반에 운영을 중단하게 되었다. 본 연구는 북한에서 활동하는 국제 NGO 단체들과 인도주의적 국제 기부자들의 자금과 도움을 받기 위해 건강권의 중요성을 밝히고 혼란스러운 상황에 대한 경각심을 고취하는 역할에 초점을 맞추며 1995-1998년간 국제 NGO들이 기본적 인권 특히 건강권을 옹호하는 과정에서 어떤 한계가 발생하는지에 대한 답을 얻고자 실시되었다.요약 (국문초록) i 목차 ii 1. 서론 1 1.1. 연구 목적 5 1.2. 기존 연구 9 1.2.1. 보건 및 건강권 옹호를 위한 NGO의 역할 9 1.2.2. 국제관계와 세계정치학에서 NGO에 대한 이론 소개와 해석 11 1.2.3. 연구 질문 18 1.3. 연구 범위 및 방법론 19 2. 1995-1998년 간 북한 및 국경 없는 의사회 활동 21 2.1. 북한 정부 요청에 따라 1995년에 활동 시작 21 2.2. 1996-1997년간 보건 및 영양 개선을 위한 운영 26 2.3. 1998년 운영 중단 및 활동 개요 34 3. 국경없는 의사회의 활동에 대한 평가 38 3.1 자체 평가 38 3.2. 외부평가 47 4. 북한에서의 NGO 활동의 어려움에 대한 재평가 56 5. 결론 71 참고문헌 76 Abstract 86Maste

The Chronicle of Yerevan Days: Spatial Representation and Authentic Realism

his article offers an insight into how space is represented in the feature film The Chronicle of Yerevan Days (Dovlatyan, 1972). I examine the film’s unmediated and minimally mediated spatial presentation of the actual city of Yerevan – its buildings and streets etc. I claim that, in narrating the fictional story, the mise-en-scène and cinematography emphasize the city’s spaces. The manner in which the buildings, streets, and squares are highlighted suggests that the city acts as an agent. I use Koppelhoff’s (2012) theory of “diegetic space,” Alter’s (2005) idea of “mythographer,” and da Costa’s (2015) notion of the urban environment as mise-en-scène to argue that authentic realism arises from the deployment in real time of the city as an agent in The Chronicle of Yerevan Days. At the core of my argument lies the claim that the film’s narrative integrates objective documentary narration with fictional storytelling. The mise-en-scène and cinematography selectively represent details and fragments of city spaces and buildings, which equip the represented city with a certain agency. In this function, the city interacts with the human characters. My claim about authentic realism stems from the fact that the buildings, streets, and squares in the film are historically accurate in function. This creates for the viewer an intense familiarity. Also, by virtue of their historical and cultural values, the represented buildings and streets contextualize the story as Armenian, infusing a sense of authenticity into the characters and their actions

A search for peculiar stars in the open cluster Hogg 16

The study of chemically peculiar (CP) stars in open clusters provides valuable information about their evolutionary status. Their detection can be performed using the $\Delta a$ photometric system, which maps a characteristic flux depression at $\lambda \sim 5200$ \AA. This paper aims at studying the occurrence of CP stars in the earliest stages of evolution of a stellar population by applying this technique to Hogg 16, a very young Galactic open cluster (about 25 Myr). We identified several peculiar candidates: two B-type stars with a negative $\Delta a$ index (CD-60 4701, CPD-60 4706) are likely emission-line (Be) stars, even though spectral measurements are necessary for a proper classification of the second one; a third object (CD-60 4703), identified as a Be candidate in literature, appears to be a background B-type supergiant with no significant $\Delta a$ index, which does not rule out the possibility that it is indeed peculiar as the normality line of $\Delta a$ for supergiants has not been studied in detail yet. A fourth object (CD-60 4699) appears to be a magnetic CP star of 8 M$_\odot$, but obtained spectral data seem to rule out this hypothesis. Three more magnetic CP star candidates are found in the domain of early F-type stars. One is a probable nonmember and close to the border of significance, but the other two are probably pre-main sequence cluster objects. This is very promising, as it can lead to very strong constraints to the diffusion theory. Finally, we derived the fundamental parameters of Hogg 16 and provide for the first time an estimate of its metal content.Comment: Accepted for publication in New Astronomy. 9 pages, 4 figures, and 4 tables. A complete data table is available via CDS or upon request from the corresponding autho