Literatura académica sobre el tema "Complement alternative passkey"

Abstract A complement-resistant line of HeLa cells (T638) was derived by serial passage of complement-susceptible HeLa cells in anti-beta 2-microglobulin (b2m) antiserum and complement. The T638 line maintained stable complement resistance when passed for an additional 1500 generations in the absence of antiserum and complement. T638 cells expressed equivalent levels of cell-associated b2m as did the parent HeLa cell line. Furthermore, T638 cells were resistant to killing by complement and anti-HeLa antiserum with specificity for molecules other than b2m. These results indicate that the resistance of T638 cells does not simply reflect loss of anti-b2m binding antigens. We next investigated the mechanism of resistance of T638 cells to complement-mediated killing. Antibody-sensitized HeLa and T638 cells both consumed CH50 activity completely from normal human serum; cytotoxicity was not mediated via the alternative complement pathway. HeLa and T638 cells caused equivalent utilization of C4 from normal human serum in the presence of antibody. Consumption of C2, greater with T638 than with HeLa cells during incubation in serum, was complete when cells bearing purified C1 and limited C4 were incubated with C2. T638 cells bound more 3H-C4 than HeLa cells during incubation in serum, but binding of 3H-C3 by T638 cells was fourfold to fivefold less than by HeLa cells. Finally, we investigated the rate of decay in the capacity of C142 on HeLa and T638 to cleave and deposit 3H-C3. The T1/2 for decay of C142-mediated binding of 3H-C3 on HeLa was 3.9 min, whereas minimal C3 deposition was detected on T638 cells at all time points. These results show that T638 cells evade complement-mediated lysis despite activating early components of the classical complement pathway. The mechanism of resistance is a failure to form an effective C3 convertase.

Currently, unmanned vehicles are widely used in different fields of exploration. Due to limited capacities, such as limited power supply, it is almost impossible for one unmanned vehicle to visit multiple wide areas. Multiple unmanned vehicles with well-planned routes are required to minimize an unnecessary consumption of time, distance, and energy waste. The aim of the present study was to develop a multiple-vehicle system that can automatically compile a set of optimum vehicle paths, complement failed assignments, and avoid passing through no-travel zones. A heuristic algorithm was used to obtain an approximate solution within a reasonable timeline. The A* Search algorithm was adopted to determine an alternative path that does not cross the no-travel zone when the distance array was set, and an improved two-phased Tabu search was applied to converge any initial solutions into a feasible solution. A diversification strategy helped identify a global optimal solution rather than a regional one. The final experiments successfully demonstrated a group of three robot cars that were simultaneously dispatched to each of their planned routes; when any car failed during the test, its path was immediately reprogrammed by the monitoring station and passed to the other cars to continue the task until each target point had been visited.

Abstract Eight years have passed since the approval of belimumab, a monoclonal antibody directed against B lymphocyte stimulation and the first targeted therapy approved for systemic lupus. erythematous (SLE). While well tolerated, the efficacy of belimumab remains limited and is not recommended for patients suffering severe nephritis, a life threatening complication of SLE. We sought to explore alternative targets of autoreactive B lymphocytes through manipulation of affinity maturation. The BXSB model is a long established model of human SLE developing elevated antinuclear antibodies and immune complex nephritis along with other manifestations of autoimmune disease. We used CRISPR-Cas9 to inactivate Activation Induced Cytidine Deaminase (Aicda, AID) directly in the BXSB background and found greatly improved survival. While mice continued to develop plasma cells, follicular structure was restored and renal pathology was reduced. While antinuclear antibody concentrations were reduced in knockout mice, renal immune complex deposition was grossly the same as wild type while complement deposition was very limited in the knockout mice. Mice develop expanded germinal center B cell populations as in other models of AID deficiency without concurrent expansion of follicular T cells. The prolonged survival in these mice appears to be attributed to the reduced renal pathology warranting further exploration as current therapeutics targeting lupus nephritis are limited and thus in great demand.

Background: Radiation retinopathy is a major cause of vision loss in patients receiving radiotherapy to the head and orbit. Diabetic retinopathy is included in the differential diagnosis owing to similar clinical features, including microaneurysms, cotton-wool spots, hard exudates, and macular edema. The only significant pathological difference is that radiation retinopathy spares pericytes, unlike diabetic retinopathy. Multimodal imaging helps diagnose and predict the prognosis of radiation retinopathy, which is presented in this case report. Case Presentation: A 55-year-old woman diagnosed with stage-4 metastatic breast carcinoma presented with gradual diminution of vision in the left eye (OS) over 5 months. Vision in the right eye was lost because of orbital radiotherapy for orbital metastasis. The patient underwent multiple sessions of chemotherapy and radiotherapy. Examination of the left eye revealed a best-corrected distance visual acuity (BCDVA) of 20/30. Fundus examination of the OS revealed multiple cotton-wool spots and retinal hemorrhages. Fundus fluorescein angiography (FFA) showed diffuse macular leakage with capillary nonperfusion. Multicolor imaging (MCI) with Spectralis™ revealed black dots in the blue and green reflectance images, corresponding to capillary dilatation on FFA. Darker dots were more evident in the infrared images. BCDVA improved to 20/20 in OS after tapering the dose of oral steroids for 2 months, with improvements in hemorrhages and cotton-wool spots. Focal laser photocoagulation was recommended for the treatment of persistent macular edema. The patient declined further treatment, was lost to follow-up, and passed away 6 months later. Conclusions: This case highlights the importance of multimodal imaging for the identification and classification of radiation retinopathy. MCI using SpectralisTM has been described for the first time in radiation retinopathy and can be used to complement existing imaging modalities. Future studies involving more patients and a longer follow-up duration may provide better results for the applicability of these imaging modalities in the clinical setting.

Abstract Background: Paroxysmal Nocturnal Hemoglobinurea (PNH) is a rare stem cell disease caused by the expansion of PIGA mutated clone(s). PNH-type cells are deficient in the expression of GPI-anchored proteins including DAF and CD59, which protect red blood cells (RBC) from complement-mediated intravascular hemolysis. Eculizumab (Soliris®, Alexion Pharmaceuticals) is a humanized monoclonal antibody against C5 which efficiently inhibits hemolysis by blocking the terminal complement cascade. Eculizumab dramatically ameliorates several clinical symptoms, and improves the prognosis in PNH patients. However, among 345 Japanese PNH patients who were treated with eculizumab, 11 patients showed poor response. All the poor responders had a single missense C5 heterozygous mutation, c.2654G>A, which predicts the polymorphism p.Arg885His (Nishimura et al, NEJM. 2014 13;370(7):632-9). Two of those patients have already passed away due to severe complications related to PNH, and the rest of them are still suffered from various clinical symptoms including hemolytic episodes and RBC transfusion. In these circumstances, multiple new anti-complement drugs are under development in Japan. Coversin (Volution Immuno Pharmaceuticals) is a recombinant protein (16,740 Da) derived from a secreted protein in the saliva of the Ornithodoros moubata tick, and it blocks complement-mediated hemolysis at C5 level. In this study, we examined this new anti-complement agent to a PNH patient with C5 polymorphism c.2654G>A, as well as those without the polymorphism. Materials: Peripheral blood samples were collected from a poor responder to eculizumab and hemolytic PNH patients with written informed consent as approved by the Institutional Review Board of Osaka University Hospital. In vitro hemolytic assay: RBC from ABO-matched PNH patients off eculizumab treatment were washed 3 times in saline, and subsequently incubated with Mg2+ supplemented serum of the poor responder in the presence or absence of an anti-complement agent. Alternative pathway was activated by adding HCl (22:1 of 0.4M HCl) to the serum. Heat-inactivated (56°C for 30min) serum was used as a negative control. After a 24-hour incubation at 37°C, hemolysis was quantified by measuring the optical density at 405nm (OD405). The hemolytic activity was normalized against maximum hemolysis as induced by HCl (100%) and minimum hemolysis with inactivated acidified serum (0%). Results: A 41-year-old male with fatigue was diagnosed as aplastic anemia with PNH in 2008, and cyclosporine (CyA) was initiated at the dose of 150mg/day. The PNH clone expanded from 30.6% to 70.2% in granulocytes from 2008 to 2011 with elevated LDH (700 U/L) and the patient was referred to our hospital to undergo eculizumab treatment. CyA was reduced to 100mg/day and eculizumab was initiated in May 2012. Eculizumab treatment did not change the serum LDH level without any improvement of the symptoms: fatigue, abdominal pain, and periodical hemoglobinurea. A heterozygous mutation c.2654G>A was identified as the cause of the failure to eculizumab treatment, and he is still suffered from continuous intravascular hemolysis (LDH > 1400 U/L) with periodical acute hemolytic episodes, requiring frequent RBC transfusion. In the hemolytic assay, Coversin completely blocked hemolysis at the concentration of 10ug/ml, similar to the effective inhibition with hemolytic PNH patients without the polymorphism. Discussion: Eculizumab has dramatically improved the quality-of-life in the majority of the PNH patients by blocking intravascular hemolysis, but there are still some concerns; poor response due to C5 polymorphism, C3b deposition on the RBC, high cost and burden for scheduled infusion. Blocking the complement cascade at C5 level has shown to be relatively safe if meningococcal vaccination is properly performed, but still an extravascular hemolysis remains problematic at least in some cases. Inhibiting C3 amplification would resolve both intra and extravascular hemolysis, but susceptibility to infections remains a major concern. Our study showed that Coversin efficiently blocked in vitro hemolysis in the eculizumab resistant patient with C5 heterozygous mutation, c.2654G>A. Coversin might be a therapeutic option for the population of C5 polymorphism c.2654G>A in PNH patients. Our results warrant further investigation to explore new anti-complement agents for hemolytic PNH patients. Disclosures Ueda: Alexion Pharma: Research Funding. Osato:Alexion Pharma: Research Funding. Weston-Davies:Volution Immuno Pharmaceuticals (UK) Ltd: Employment, Equity Ownership. Nunn:Volution Immuno Pharmaceuticals: Employment, Equity Ownership. Hayashi:Alexion Pharma: Research Funding. Nishimura:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Kanakura:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Henry & Cottell (2007) argue that Belfast English (BE) sentences such asThere shouldn't anybody say thatandThere've lots of people passed the testare transitive expletive constructions (TECs) similar to those that are a feature of Icelandic. They propose that the difference between BE and Standard English (SE) is that whereas expletivethereis introduced in Spec vP in the latter it is introduced in Spec TP in the former. On the assumption that transitive subjects originate in Spec vP, this entails that expletivetherecannot co-occur with a transitive verb. While it is clear that BE is different from SE in this area, it is not clear that BE has TECs while SE does not. There are a variety of examples which are acceptable in BE but not SE which do not seem to be TECs. SE also has certain examples which might be called TECs. The result of this is that Henry & Cottell's analysis is not very successful. It seems that what distinguishes BE from SE is not what verbs may follow the associate of the expletive but what elements may precede it. SE allows an associate immediately afterbe, but BE also allows an associate immediately after modals andhave, and for some speakersseemandlikelyas well. The facts can be captured in Head-driven Phrase Structure Grammar by assuming thatbehas an extra lexical description with expletivethereas its subject and the associate as an extra complement in both varieties of English, and that modals andhave, and for some speakersseemandlikelyas well, have an extra lexical description of this form in BE. Generalizations can be captured if the pairs of lexical descriptions are analysed as alternative ways of fleshing out basic underspecified lexical descriptions.

Este escrito apresenta os atravessamentos dos (a)muros na educação contemporânea enquanto representações insurgentes às consequências da modernidade. Esta temática emerge ante a construção do objeto de pesquisa, em fase de doutoramento, no cenário educativo do Programa Pós-graduação em Educação e Contemporaneidade da Universidade do Estado da Bahia. A tese doutoral se institui em torno da constituição do professor-sujeito frente aos (a)muros da educação contemporânea. Estes (a)muros, expressão lacaniana, rementem ao ato de castração do sujeito (ou de negação desse processo), ao tempo, que manifesta a ideia de sujeito do desejo, faltante. Assim, pelos estudos bibliográficos, foi possível elevar o sentido de (pós-)modernidade e de contemporaneidade, levando-nos a vincular os (a)muros e a noção de professor-sujeito às significações das consequências de modernidade. Ao final, alcançamos novos caminhos para pensar a subjetividade docente no cenário educacional, além de nos orientar à constituição de passes para a apreensão de representações outras acerca de suas implicações na contemporaneidade.Educação. Contemporaneidade. (A)muros. Subjetivação docente.ABSTRACTThis writing presents the crossing of (a) walls in contemporary education as insurgent representations to the consequences of modernity. This theme emerges before the construction of the research object, in the doctoral stage, in the educational scenario of the Postgraduate Program in Education and Contemporary at the State University of Bahia. The doctoral thesis is instituted around the constitution of the teacher-subject before the (a) walls of contemporary education. These (a) walls, Lacanian expression, complement of the subject's act of castration (or denial of this process), at the time, which manifests the missing subject's idea of the subject. Thus, through bibliographic studies, it was possible to raise the sense of (post-) modernity and contemporaneity, leading us to link the walls to the meanings of the consequences of modernity. In the finaly, we apprehend that the interpretative readings unveiled new ways to think about the subjectivity of teachers in the contemporary education scenario, in addition to guiding us to the constitution of passes to search for alternatives other to the implications of modernity.Education. Contemporaneity. (A)walls. Teaching subjectification. RESUMENEste artículo presenta los cruces de (a)muros en la educación contemporánea como representaciones insurgentes a las consecuencias de la modernidad. Este tema surge delante de la construcción del objeto de investigación, en la etapa de doctorado, en el escenario educativo del Programa de Posgrado en Educación y Contemporánea de la Universidad do estado da Bahia. La tesis doctoral se instituye en torno a la constitución del profesor-sujeto ante los (a)muros de la educación contemporánea. Estos (a)muros, expresión lacaniana, remiten al acto de castración del sujeto (o negación de este proceso), al tiempo que manifiesta la idea de sujeto del deseo, faltante. Así, a través de los estudios bibliográficos se logró elevar el sentido de (pos) modernidad y contemporaneidad, llevándonos a vincular los (a)muros y la noción de docente-sujeto con los significados de las consecuencias de la modernidad. Al final, llegamos a nuevas formas de pensar la subjetividad docente en el escenario educativo, además de orientarnos a la constitución de pases para la aprehensión de otras representaciones sobre sus implicaciones en la época contemporánea.Educación. Tiempo contemporáneo. (A) paredes. Subjetivación docente.

Background: Despite being acknowledged worldwide as essential maternal care providers, midwives remain marginalized in the Jordanian healthcare system. Further, considering Jordan’s goal to achieve a total fertility rate of 2.1 by 2030 and Jordanian women’s preference for female providers, enhancing midwives’ role could significantly promote the use of reproductive health and family planning services. Focus of the Article: We report on opportunities created by opening the boundary of our social marketing understanding to systems thinking in practice (STiP), using soft systems methodology (SSM) to engage with the complex situation of midwifery policy in Jordan. Research Question: In what ways could STiP benefit upstream social marketing interventions? We attempt to answer this question from the perspective of an SSM action research in Jordan. Program Design/Approach: The intervention combines stakeholder analysis and evidence-based policy with an SSM seven-stage cycle. We analyze the compatibility of SSM with social marketing through the NSMC’s eight benchmark criteria. Importance to the Social Marketing Field: The case offers to learn experientially about the relevance of a systems’ approach to complement social marketing frameworks. Drawing from the practical application of SSM, this study suggests that using systems’ tools in social marketing interventions might significantly contribute to achieving intended behavioral outcomes. Methods: Gordon’s alternative framework for upstream social marketing, “advocacy, relationship building and stakeholders’ engagement,” was enacted through the SSM’s seven stages. Research findings provided advocacy arguments. Rich pictures, conceptual modeling, and the CATWOE exercise fostered relationship building and stakeholders’ engagement toward the accommodation stage. Results: At the systematic level, that is, the linear chain of programmatic activities, the policy objective was achieved with an amended Law submitted to the Parliament for debate. At the systemic level, that is, the dynamic relationships among stakeholders, the social learning that emerged during the SSM process reduced policymakers’ resistance and fostered their collective action. Recommendations for Research or Practice: Social marketers can benefit from further experimentation with systems’ approaches to develop their STiP capabilities. Thus, social marketing practice, at this historical moment, could be better equipped conceptually and practically to manage for the emergence of positive behavior change in messy upstream situations where policy and politics are always enmeshed. Limitations: SSM calls for several iterations until stakeholders feel that no more change is needed. However, these iterations are challenging to implement during the limited time frame of development projects. In this case, another iteration was suggested to diffuse the conflict between midwives and obstetrician-gynecologists who saw themselves as victims of this policy reform. However, with Jordan Communication Advocacy and Policy ending in December 2019, this case legacy might be passed on to other projects.

Background: The integration of ethnomedicine into primary medicine has become an increasingly relevant topic in recent decades. Ethnomedicine, which refers to traditional healing practices passed down through generations and used by various cultures worldwide, offers significant potential to complement modern medical practices. Objective: This literature review aims to explore the potential created by the integration of ethnomedicine into primary medicine. Methods: This review utilizes a literature review method across multiple databases such as PubMed, Google Scholar, and SCISPACE. Results: Ethnomedicine, with its holistic approach, can enhance healthcare delivery and provide insights into alternative health practices. The integration of ethnomedicine with primary medical sciences offers significant potential to create a more comprehensive functional medicine, focusing on the root causes of diseases and emphasizing prevention and the maintenance of optimal health. Conclusion: The integration of ethnomedicine with primary medicine can create healthcare solutions that enhance the overall well-being of patients.

Introduction Artist: June 2 at 11.26pm:‘To be truly radical is to make hope possible rather than despair convincing.’ - Raymond Williams. (Singaporean Artists’ public Facebook Post) Can the critical arts exist without ‘place’?There is an ongoing debate on ‘place’ and where it begins and ends; on the ways that cities exist in both material and immaterial forms, and thereby, how to locate and understand place as an anchoring point amidst global flows (Massey; Merrifield). This debate extends to the global art- scape, as traditional conceptions of art and art-making attached to place require re-thinking in a paradigm where digital and immaterial networks, symbols and forums both complement and complicate the role that place has traditionally played (Luger, “Singaporean ‘Spaces of Hope?”). The digital art-scape has allowed for art-led provocations, transformations and disturbances to traditional institutions and gatekeepers (see Hartley’s “ Communication, Media, and Cultural Studies” concept of ‘gatekeeper’) of the art world, which often served as elite checkpoints and way-stations to artistic prominence. Still, contradictory and paradoxical questions emerge, since art cannot be divorced of place entirely, and ‘place’ often features as a topic, subject, or site of critical expression for art regardless of material or immaterial form. Critical art is at once place-bound and place-less; anchored to sites even as it transcends them completely.This paper will explore the dualistic tension – and somewhat contradictory relationship – between physical and digital artistic space through the case study of authoritarian Singapore, by focusing on a few examples of art-activists and the way that they have used and manipulated both physical and digital spaces for art-making. These examples draw upon research which took place in Singapore from 2012-2014 and which involved interviews with, and observation of, a selected sample (30) of art-activists (or “artivists”, to use Krischer’s definition). Findings point to a highly co-dependent relationship between physical and digital art places where both offer unique spaces of possibility and limitations. Therefore, place remains essential in art-making, even as digital avenues expand and amplify what critical art-practice can accomplish.Singapore’s Place-Bound and Place-Less Critical Art-Scape The arts in Singapore have a complicated, and often tense relationship with places such as the theatre, the gallery, and the public square. Though there has been a recent push (in the form of funding to arts groups and physical arts infrastructure) to make Singapore more of an arts and cultural destination (see Luger “The Cultural Grassroots and the Authoritarian City”), the Singaporean arts-scape remains bound by restrictions and limitations, and varying degrees of de facto (and de jure) censorship and self-policing. This has opened up spaces for critical art, albeit in sometimes creative and surprising forms. As explained to me by a Singaporean playwright,So they’re [the state] making venues, as well as festival organizers, as well as theatre companies, to …self-police, or self-censor. But for us on the ground, we use that as a way to focus on what we still want to say, and be creative about it, so that we circumvent the [state], with the intention of doing what we want to do. (Research interview, Singaporean playwright)Use of cyber-spaces is one way that artists circumvent repressive state structures. Restrictions on the use of place enliven cyberspace with an emancipatory and potentially transformative potential for the critical arts. Cyber-Singapore has a vocal art-activist network and has allowed some artists (such as the “Sticker Lady”) to gain wide national and even international followings. However, digital space cannot exist without physical place; indeed, the two exist, simultaneously, forming and re-forming each other. The arts cannot ‘happen’ online without a corresponding physical space for incubation, for practice, for human networking.It is important to note that in Singapore, art-led activism (or ‘artivism’) and traditional activism are closely related, and research indicated that activist networks often overlap with the art world. While this may be the case in many places, Singapore’s small geography and the relatively wide-berth given to the arts (as opposed to political activism) make these relationships especially strong. Therefore, many arts-spaces (theatres, galleries, studios) function as activist spaces; and non-art spaces such as public squares and university campuses often host art events and displays. Likewise, many of the artists that I interviewed are either directly, or indirectly, involved in more traditional activism as well.Singapore is an island-nation-city-state with a carefully planned urban fabric, the vast majority of which is state-owned (at least 80 % - resulting from large-scale land transfers from the British in the years surrounding Singapore’s independence in 1965). Though it has a Westminster-style parliamentary system (another colonial vestige), a single ruling party has commanded power for 50 years (the People’s Action Party, or PAP). Despite free elections and a liberal approach toward business, foreign investment and multiculturalism, Singapore retains a labyrinthine geography of government control over free expression, dictated through agencies such as the Censorship Review Committee (CRC); the Media Development Authority (MDA), and the National Arts Council (NAC) which work together in a confusing grid of checks and balances. This has presented a paradoxical and often contradictory approach to the arts and culture in which gradual liberalisations of everything from gay nightlife to university discourse have come hand-in-hand with continued restrictions on political activism and ‘taboo’ artistic / cultural themes. These ‘out of bounds’ themes (see Yue) include perceived threats to Singapore’s racial, religious, or political harmony – a grey area that is often at the discretion of particular government bureaucrats and administrators.Still, the Singaporean arts place (take the theatre, for example) has assumed a special role as a focal point for not only various types of visual and performance art, but also unrelated (or tangentially-related) activist causes as well. I asked a theatre director of a prominent alternative theatre where, in Singapore’s authoritarian urban fabric, there were opportunities for provocation? He stressed the theatres’ essential role in providing a physical platform for visual tensions and disturbance:You know, and on any given evening, you’ll see some punks or skinheads hanging outside there, and they kind of – create this disturbance in this neighbourhood, where, you know a passer-by is walking to his posh building, and then suddenly you know, there’s this bunch of boys with mohawks, you know, just standing there – and they are friendly! There’s nothing antagonistic or threatening, whatever. So, you know, that’s the kind of tension that we actually love to kind of generate!… That kind of surprise, that kind of, ‘oh, oh yes!’ we see this nice, expensive restaurant, this nice white building, and then these rough edges. And – that is where uh, those points where – where factions, where the rough edges meet –are where dialogue occurs. (Theatre Director, Singapore)That is not to say that the theatre comes without limits and caveats. It is financially precarious, as the Anglo-American model of corporate funding for the arts is not yet well-established in Singapore; interviews revealed that even much of the philanthropic donating to arts organizations comes from Singapore’s prominent political families and therefore the task of disentangling state interests from non-ideological arts patronage becomes difficult. With state - funding come problems with “taboo” subjects, as exemplified by the occasional banned-play or the constant threat of budget cuts or closure altogether: a carrot and stick approach by the state that allows arts organizations room to operate as long as the art produced does not disturb or provoke (too) much.Liew and Pang suggest that in Singapore, cyberspace has allowed a scale, a type of debate and a particularly cross-cutting conversation to take place: in a context where there are peculiar restrictions on the use and occupation of the built environment. They [ibid] found an emerging vocal, digital artistic grassroots that increasingly challenges the City-State’s dominant narratives: my empirical research therefore expands upon, and explores further, the possibility that Singapore’s cyber-spaces are both complementary to, and in some ways, more important than its material places in terms of providing spaces for political encounters.I conducted ‘netnography’ (see Kozinets) across Singapore’s web-scape and found that the online realm may be the ‘… primary site for discursive public activity in general and politics in particular’ (Mitchell, 122); a place where ‘everybody is coming together’ (Merrifield, 18). Without fear of state censorship, artists, activists and art-activists are not bound by the (same) set of restrictions that they might be if operating in a theatre, or certainly in a public place such as a park or square. Planetary cyber-Singapore exists inside and outside the City-State; it can be accessed remotely, and can connect with a far wider audience than a play performed in a small black box theatre.A number of blogs and satirical sites – including TheOnlineCitizen.sg, TheYawningBread.sg, and Demon-Cratic Singapore, openly criticize government policy in ways rarely heard in-situ or in even casual conversation on the street. Additionally, most activist causes and coalitions have digital versions where information is spread and support is gathered, spanning a range of issues. As is the case in material sites of activism in Singapore, artists frequently emerge as the loudest, most vocal, and most inter-disciplinary digital activists, helping to spearhead and cobble together cultural-activist coalitions and alliances. One example of this is the contrast between the place bound “Pink Dot” LGBTQ event (limited to the amount of people that can fit in Hong Lim Park, a central square) and its Facebook equivalent, We are Pink Dot public ‘group’. Pink Dot occurs each June in Singapore and involves around 10,000 people. The Internet’s representations of Pink Dot, however, have reached millions: Pink Dot has been featured in digital (and print) editions of major global newspapers including The Guardian and The New York Times. While not explicitly an art event, Pink Dot is artistic in nature as it uses pink ‘dots’ to side-step the official designation of being an LGBTQ pride event – which would not be sanctioned by the authorities (Gay Pride has not been allowed to take place in Singapore).The street artist Samantha Lo – also known as “Sticker Lady” – was jailed for her satirical stickers that she placed in various locations around Singapore. Unable to freely practice her art on city streets, she has become a sort of local artist - Internet celebrity, with her own Facebook Group called Free Sticker Lady (with over 1,000 members as of April, 2016). Through her Facebook group, Lo has been able to voice opinions that would be difficult – or even prohibited – with a loudspeaker on the street, or expressed through street art. As an open lesbian, she has also been active (and vocal) in the “Pink Dot” events. Her speech at “Pink Dot” was heard by the few-thousand in attendance at the time; her Facebook post (public without privacy settings) is available to the entire world:I'll be speaking during a small segment at Pink Dot tomorrow. Though only two minutes long, I've been spending a lot of time thinking about my speech and finding myself at a position where there's just so much to say. All my life, I've had to work twice as hard to prove myself, to be taken seriously. At 18, I made a conscious decision to cave in to societal pressures to conform after countless warnings of how I wouldn't be able to get a job, get married, etc. I grew my hair out, dressed differently, but was never truly comfortable with the person I became. That change was a choice, but I wasn't happy.Since then, I learnt that happiness wasn't a given, I had to work for it, for the ability to be comfortable in my own skin, to do what I love and to make something out of myself. (Artists’ Facebook Post)Yet, without the city street, Lo would not have gained her notoriety; without use of the park, Pink Dot would not have a Facebook presence or the ability to gather international press. The fact that Singaporean theatre exists at all as an important instigator of visual and performative tension demonstrates the significance of its physical address. Physical art places provide a crucial period of incubation – practice and becoming – that cannot really be replicated online. This includes schools and performance space but also in Singapore’s context, the ‘arts-housing’ that is provided by the government to small-scale, up-and-coming artists through a competitive grant process. Artists can receive gallery, performance or rehearsal space for a set amount of time on a rotating basis. Even with authoritarian restrictions, these spaces have been crucial for arts development:There’s a short-term [subsidised] residency studio …for up to 12 months. And so that –allows for a rotating group of artists to come with an idea in mind, use it for whatever- we’ve had artists who were preparing for a major show, and say ‘my studio space, my existing studio space is a bit too tiny, because I’m prepping for this show, I need a larger studio for 3 months. (Arts Administrator, Singapore)Critical and provocative art, limited and restricted by place, is thus still intrinsically bound to it. Indeed, the restrictions on artistic place allow cyber-art to flourish; cyber-art can only flourish with a strong place- based anchor. Far from supplanting place-based art, the digital art-scape forms a complement; digital and place-based art forms combine to form new hybridities in which local context and global forces write and re-write each other in a series of place and ‘placeless’ negotiations. Conclusion The examples that have been presented in this paper paint a picture of a complex landscape where specific urban sites are crucial anchoring nodes in a critical art ecosystem, but much artistic disturbance actually occurs online and in immaterial forms. This may hint at the possibility that globally, urban sites themselves are no longer sufficient for critical art to flourish and reach its full potential, especially as such sites have increasingly fallen prey to austerity policies, increasingly corporate and / or philanthropic programming and curation, and the comparatively wider reach and ease of access that digital spaces offer.Electronic or digital space – ranging from e-mail to social media (Twitter, blogs, Facebook and many others) has opened a new frontier in which, “… material public spaces in the city are superseded by the fora of television, radio talk shows and computer bulletin boards” (Mitchell. 122). The possibility now emerges whether digital space may be even more crucial than material public spaces in terms of emancipatory or critical potential– especially in authoritarian contexts where public space / place comes with particular limits and restrictions on assembling, performance, and critical expression. These contexts range from Taksim Square, Istanbul to Tiananmen Square, Beijing – but indeed, traditional public place has been increasingly privatized and securitized across the Western-liberal world as well. Where art occurs in place it is often stripped of its critical potential or political messages, sanctioned or sponsored by corporate groups or sanitized by public sector authorities (Schuilenburg, 277).The Singapore case may be especially stark due to Singapore’s small size (and corresponding lack of visible public ‘places’); authoritarian restrictions and correspondingly (relatively) un-policed and un-censored cyberspace. But it is fair to say that at a time when Youtube creates instant celebrities and Facebook likes or Instagram followers indicate fame and (potential) fortune – it is time to re-think and re-conceptualise the relationship between place, art, and the place-based institutions (such as grant-funding bodies or philanthropic organizations, galleries, critics or dealers) that have often served as “gatekeepers” to the art-scape. This invites challenges to the way these agents operate and the decision making process of policy-makers in the arts and cultural realm.Mitchell (124) reminded that there has “never been a revolution conducted exclusively in electronic space; at least not yet.” But that was 20 years ago. Singapore may offer a glimpse, however, of what such a revolution might look like. This revolution is neither completely place bound nor completely digital; it is one in which the material and immaterial interplay and overlap in post-modern complexity. Each platform plays a role, and understanding the way that art operates both in place and in “placeless” forms is crucial in understanding where key transformations take place in both the production of critical art and the production of urban space.What Hartley (“The Politics of Pictures”) called the “space of citizenry” is not necessarily confined to a building, the city street or a public square (or even private spaces such as the home, the car, the office). Sharon Zukin likewise suggested that ultimately, a negotiation of a city’s digital sphere is crucial for current-day urban research, arguing that:Though I do not think that online communities have replaced face to face interaction, I do think it is important to understand the way web-based media contribute to our urban imaginary. The interactive nature of the dialogue, how each post feeds on the preceding ones and elicits more, these are expressions of both difference and consensus, and they represent partial steps toward an open public sphere. (27)Traditional gatekeepers such as the theatre director, the museum curator and the state or philanthropic arts funding body have not disappeared, though they must adapt to the new cyber-reality as artists have new avenues around these traditional checkpoints. Accordingly – “old” problems such as de-jure and de-facto censorship reappear in the cyber art-scape as well: take the example of the Singaporean satirical bloggers that have been sued by the government in 2013-2016 (such as the socio-political bloggers and satirists Roy Ngerng and Alex Au). No web-space is truly open.A further complication may be the corporate nature of sites such as Facebook, Instagram, Youtube, or Twitter: far from truly democratic platforms or “agoras” in the traditional sense, these are for-profit (massive) corporations – which a small theatre is not. Singapore’s place based authoritarianism may be multiplied in the corporate authoritarianism or “CEO activism” of tech titans like Mark Zuckerberg, who allow for diverse use of digital platforms and encourage open expression and unfettered communication – as long as it is on their terms, within company policies that are not always transparent.Perhaps the questions then really are not where ‘art’ begins and ends, or where a place starts or stops – but rather where authoritarianism, state and corporate power begin and end in the hyper-connected global cyber-scape? And, if these power structures are now stretched across space and time as Marxist theorists such as Massey or Merrifield claimed, then what is the future for critical art and its relationship to ‘place’?Despite these unanswered questions and invitations for further exploration, the Singapore case may hint at what this emerging geography of place and ‘placeless’ art resembles and how such a new world may evolve moving forward. ReferencesHartley, John. The Politics of Pictures: the Creation of the Public in the Age of Popular Media. Perth: Psychology Press, 1992.———. Communication, Media, and Cultural Studies: The Key Concepts. Oxford: Routledge, 2012. Kozinets, Robert. Netnography: Doing Ethnographic Research Online. New York: Sage, 2010. Krischer, Oliver. “Lateral Thinking: Artivist Networks in East Asia.” ArtAsia Pacific 77 (2012): 96-110. Liew, Kai Khiun. and Natalie Pang. “Neoliberal Visions, Post Capitalist Memories: Heritage Politics and the Counter-Mapping of Singapore’s City-Scape.” Ethnography 16.3 (2015): 331-351.Luger, Jason. “The Cultural Grassroots and the Authoritarian City: Spaces of Contestation in Singapore.” In T. Oakes and J. Wang, eds., Making Cultural Cities in Asia: Mobility, Assemblage, and the Politics of Aspirational Urbanism. London: Routledge, 2015: 204-218. ———. “Singaporean ‘Spaces of Hope?' Activist Geographies in the City-State.” City: Analysis of Urban Trends, Culture, Theory, Policy, Action 20.2 (2016): 186-203. Massey, Doreen. Space, Place and Gender. Minneapolis: University of Minnesota Press, 1995. Merrifield, Andy. The Politics of the Encounter: Urban Theory and Protest under Planetary Urbanization. Athens: University of Georgia Press, 2013. Mitchell, Don. “The End of Public Space? People’s Park, Definitions of the Public, and Democracy.” Annals of the Association of American Geographers 85.1 (1996): 108-133. Schuilenburg, Marc. The Securitization of Society: Crime, Risk and Social Order. New York: New York University Press, 2015. Shirky, Clay. Here Comes Everybody: The Power of Organizing without Organizations. New York: Penguin, 2008. Yue, Audrey. “Hawking in the Creative City: Rice Rhapsody, Sexuality and the Cultural Politics of New Asia in Singapore. Feminist Media Studies 7.4 (2007): 365-380. Zukin, Sharon. The Naked City: The Death and Life of Authentic Urban Places. London and New York: Oxford University Press, 2010.

La glomérulopathie à dépôts de C3 (GC3) est une glomérulopapthie rare liée à une dérégulation de la voie alterne du complément (VA), en particulier des deux enzymes clés de la cascade : les C3 et C5 convertases. Le plus souvent, elle est secondaire à l'acquisition d'un auto-anticorps ciblant la C3 convertase alterne. Plus rarement, on identifie des variants pathogènes dans les gènes codants pour les composants de la C3 convertase alterne (C3 et FB) ou les principaux régulateurs de la VA (FH et FI). La présentation clinique, histologique et immunologique (profil de biomarqueurs témoins de l'activation du complément) est hétérogène. La moitié des patients évolue vers l'insuffisance rénale terminale à 10 ans, les principaux facteurs pronostics de survie rénale sont cliniques et histologiques, non spécifiques à la GC3. Dans une première partie, nous avons caractérisé les anomalies génétiques des protéines du complément au sein de la cohorte française des GC3 en lien avec la présentation clinique, biologique et le pronostique rénal. Parmi les 398 patients ayant bénéficié d'une exploration génétique, 66 (17%) présentaient un variant rare de CFH, CFI ou C3 (75% classés pathogènes). Hormis la présence de microangiopathie thrombotique biologique, plus fréquente chez ceux avec variants de CFI, la présentation clinique n'était pas différente entre les groupes avec variants de CFH, CFI ou C3. Les patients porteurs de variants de CFH et CFI avaient une fréquence accrue de déficit quantitatif en FH et FI, sans différence dans les dosages de C3, C4, sC5b-9. Le pronostic rénal était moins bon dans le groupe avec variants (CFH, CFI ou C3) comparé aux patients sans variant. Dans une seconde partie, nous nous sommes intéressés au lien entre le profil d'activation des convertases et la réponse immunitaire intrarénale. Dans une première cohorte de GC3 (n=42) nous avons démontré que la majorité présentait une activation intra-rénale de la voie finale commune du complément (VFC) reflétée par des dépôts de C5b-9. L'importance de l'activation corrélait avec la présentation histologique et le pronostic rénal (moins bon pronostic chez les patients avec l'activation la plus importante). Une analyse transcriptomique en bulk de biopsies rénales a identifié 301/847 gènes immuns up-régulés chez les GC3 comparés aux contrôles. A partir de ces données, un clustering non supervisé a individualisé 4 groupes. Un groupe se caractérisait à la fois par un enrichissement en populations immunes et fibroblastiques (déconvoluées), plus d'activation intrarenale de la VFC, une importante chronicité histologique et une moins bonne survie rénale.Dans une seconde cohorte de GC3 (n=47), nous avons démontré qu'il existait une compartimentalisation de l'infiltrat immun intrarénal avec une majorité de neutrophiles et macrophages dans les glomérules vs une majorité de lymphocytes B, T et macrophages dans l'interstitium. Les patients avec un infiltrat glomérulaire riche en neutrophiles présentaient davantage de stigmates biologiques d'activation systémique de la VA et de la VFC, plus d'activation intrarénale de la VFC et entraient plus rapidement en rémission que ceux avec une faible densité de neutrophiles glomérulaires. A l'inverse, il n'y avait pas d'association entre l'importance de l'infiltrat immun interstitiel et le profil d'activation du complément. Les glomérules riches en neutrophiles présentaient une surexpression de gènes impliqués dans le recrutement et l'activation des neutrophiles, et dans l'acquisition d'un phénotype mésangial profibroblastique (transcriptomique spatiale). Avec l'émergence des thérapeutiques inhibitrices du complément, la meilleure compréhension du lien entre profil d'activation du complément, réponse immune intra-rénale et expression phénotypique de la pathologie ouvre la voie à une prise en charge personnalisée de ces patients
C3 glomerulopathy (C3G) is a rare glomerulopathy resulting from dysregulation of the complement alternative pathway (AP), particularly involving the two key enzymes of the cascade: the C3 and C5 convertases. Most often, it is secondary to the acquisition of an autoantibody targeting the alternative C3 convertase. More rarely, pathogenic variants are identified in the genes encoding the components of the alternative C3 convertase (C3 and FB) or the main regulators of the AP (FH and FI).The clinical, histological, and immunological presentation (biomarker profile indicating complement activation) is heterogeneous. Half of the patients progress to end-stage renal disease within 10 years; the main prognostic factors for renal survival are clinical and histological and are not specific of C3G.In the first part, we characterized the genetic abnormalities of complement proteins within the French cohort of C3G, in relation to clinical presentation, biological profile, and renal prognosis. Among the 398 patients who underwent genetic exploration, 66 (17%) had a rare variant in CFH, CFI, or C3 (75% classified as pathogenic). Aside from the presence of biological thrombotic microangiopathy, which was more frequent in those with CFI variants, the clinical presentation was not different between groups with CFH, CFI, or C3 variants. Patients with CFH and CFI variants had an increased frequency of quantitative deficiency in FH and FI, without differences in the levels of C3, C4, and sC5b-9. The renal prognosis was poorer in the group with variants (CFH, CFI, or C3) compared to patients without variants.In the second part, we explored the link between the profile of convertase activation and intrarenal immune response. In a first C3G cohort (n=42), we demonstrated that the majority had intrarenal activation of the complement terminal pathway (TP), reflected by C5b-9 deposits. The extent of activation correlated with histological presentation and renal prognosis (poorer prognosis in patients with the most significant activation). A bulk transcriptomic analysis of renal biopsies identified 301/847 upregulated immune genes in C3G compared to controls. From these data, unsupervised clustering identified four groups. One group was characterized by enrichment in immune and fibroblastic populations (deconvoluted), more intrarenal TP activation, significant histological chronicity, and poorer renal survival.In a second C3G cohort (n=47), we demonstrated compartmentalization of the intrarenal immune infiltrate with a majority of neutrophils and macrophages in the glomeruli versus a majority of B cells, T cells, and macrophages in the interstitium. Patients with a neutrophil-rich glomerular infiltrate exhibited more biological markers of systemic AP and TP activation, greater intrarenal TP activation, and entered remission more quickly than those with low glomerular neutrophil density. Conversely, there was no association between the extent of the interstitial immune infiltrate and the complement activation profile. Neutrophil-rich glomeruli showed overexpression of genes involved in neutrophil recruitment and activation and in acquiring a mesangial profibroblastic phenotype (spatial transcriptomics). With the emergence of complement inhibitory therapies, better understanding the link between complement activation profile, intrarenal immune response, and phenotypic expression of the pathology paves the way for personalized management of these patients

Abstract The Barik tight-gas sandstone in Khazzan and Ghazeer fields (Sultanate of Oman) is at the borderline between conventional and unconventional gas field development. Elements of complexity include efficiency of massive hydraulic fractures relative to rock types, commingled reservoirs production, differential depletion, condensate, and water presence. Managing the depletion plan requires a robust surveillance plan; a customized flow diagnostic program was designed to monitor the wells and reservoirs in the fields. The objective of this work is to describe the implementation and results of an alternative surveillance workflow that combines multiple vendors flow diagnostic instrumentations of production logs (PL), multi-detector pulsed neutron (MDPN) and surface flow meters in a science well. Traditional methods such as conventional production logs failed to deliver tangible results in the two tight reservoirs. The incumbent sensors can be used for gross flow profiling and zonal split but are limited in identifying the fluid phases separately. A reassessment of conveyance indicated that surface readout can broaden the sensors usage and provide a better option for data quality control and optimize the stationary data acquisition. Alternative flow diagnostic technologies identified for further logoff using a "science" well where a MDPN instrumentation was deployed to complement the data gathered using two independent flow diagnostic toolstrings. The manuscript describes the benefits and limitations of various sensors for multiple well conditions and reservoir properties. We combine multi-vendor flow diagnostic tools with MDPN-derived nuclear attributes (NA) to independently assess downhole condensate liquid yield. Observations indicate that fluid capacitance, acoustic and radioactive fluid density devices have almost no sensitivity to liquid phase in flowing passes; shut-in data provide very limited information of liquids which is too uncertain to be quantified. The most robust measurement for fluid phase determination consists of an array of local probes in the flow diagnostic tool; good fluid sensitivity was picked in both flowing and shut-in passes. This was complemented with the extraction of a new MDPN nuclear attribute responding to condensate in borehole. Additional MDPN nuclear attributes were used to assess the change in saturation components, including condensate. The bespoke workflow provides an efficient way to evaluate sensitivity of various sensors to pick up responses of multiple fluid phases flowing through perforations. Understanding fluids behaviour is a critical step in sensors selection, data processing and integration. Fluid holdups along with MDPN derived saturation are integrated to open-hole petrophysical rock quality interpretation to have a proper static to dynamic reservoir characterization. The condensate yield from wireline data is in close agreement with the estimation of volume fraction of vapor phase and liquid phase at borehole conditions, based on the equation of state. The workflow can be replicated in analogue environments to interpret multi-phase flow and to assess viability of comingled production with a secondary producing target.

“Kratua Thaeng Suea” is a story of hunting the tigers that trespass into town. It is a Thai traditional folk play which has been passed down from generation to generation for more than 200 years. However, this folk play is rapidly fading away from the Thai society due to the change of aesthetic preference which caused its unpopularity. Nowadays, there are only two troupes left in Bangkok which recently one of them decided to discontinue their show because of COVID-19 situation. How to preserve this intangible cultural heritage and combine it with modern aesthetics for transmission is an urgent issue. This study combines literature research and field trip methods in order to identify some of the problems faced in the dissemination of it. The research results show that, in order to renew this folk play that complement the new aesthetic preference, all related elements of this play such as its story, costumes, music, and performance need to be modernized. The new play will combine “Street Culture” such as street art, street fashion, street music, and street performance into the play with a new storyline which is twisted from the story of a tiger hunter to be rescuing the tigers instead. All of this could draw some attention from the society and thus achieve the goal of sustainable inheritance and preservation of this folk play. The new concept of “Kratua Thaeng Suea” is the combination between the old and the new which does not only reflect the beauty of cultural dynamic or build up the sense of ecological awareness in the form of “Soft Power”, but also provides a “Cultural Revitalizing model” which could be an alternative model to inherit the culture.