Examined by the plattenbau-series WBS 70 of the former DDR

Dissertação de Mestrado Integrado em Arquitetura, com a especialização em Arquitetura apresentada na Faculdade de Arquitetura da Universidade de Lisboa para obtenção do grau de Mestre.Ponto de partida: Berlim Oriental, Alemanha, 1961. A RDA procurava uma economia descentralizada e igualdade social para os seus cidadãos, o que significava que os contractos de arrendamento na habitação, só era permitida e contratada pelo Estado. Os alugueres devem ser acessíveis para todos os moradores. Rendimentos não devem decidir sobre as condições de habitação. Sob essas condições, o Regime RDA iniciou um grande programa de construção em 1973, que deveria resolver os pricipais problemas de habitacionais - como um problema social - até 1990. Após a queda do muro, a quase 30 anos atrás, as cidades do interior estavam em mau estado - e muitos dos recentes edifícios pré-fabricados já estavam a precisar de reforma. Todos os cidadãos da RDA tinham o direito à habitação adequada – este direito era protegido pela constituição. Mas, na realidade, a procura por casa e a sua escasses estavam a crescer e as condições de vida não eram, de longe, tão gloriosas quanto o planeado. Embora as condições de vida na antiga RDA já tenham sido amplamente estudadas por muitos cientistas, este trabalho incorpora os resultados já existentes da pesquisa, que comprovam como os antigos moradores vivenciaram uma injustiça no que toca à habitação. Além disso, esses resultados declarados são cobertos e comparados com informações empíricas de pesquisa, a fim de esclarecer a origem do erro, de um ponto de vista arquitetônico. Para as afirmações mencionadas, os dados empíricos foram recolhidos na forma de entrevistas com ex-residentes de WBS 70. Essas entrevistas foram gravadas, transcritas, traduzidas, analisadas e finalmente comparadas com os resultados anteriores. As páginas seguintes apresentam a principal causa de insatisfação, a dramatica escasses de espaço habitacional que teve um impacto negativo em toda a vida social. A grande maioria de todos os sujeitos foi afetada por esse problema e, de acordo com suas declarações, a grande maioria dos moradores de Berlim Oriental experienciou problemas semelhantes. No entanto, esta questão dificilmente pode ser rastreada até uma falha em termos de arquitetura, mas muito mais uma falha a nivel político. No entanto, também surgiram características positivas. Nesse sentido, este trabalho chega à conclusão de que as situações arquitetônicas do interior influenciam e muito o bem-estar social dos moradores. Com relação à série de construção de habitações WBS 70, torna-se claro que existiu também um impacto negativo. Os habitantes eram muito limitados no seu desenvolvimento pessoal, o que os obrigou a desenvolver soluções evasivas e a confiar mais na comunicação social e na cooperação. Com efeito, as limitações da série WBS 70 levaram seus habitantes a desenvolver sua personalidade de maneira próspera.ABSTRACT: Point of departure: East-Berlin, Germany, 1961. The former DDR pursued a decentralized economy and social equality for its citizens, which meant that housing, in means of renting an apartment, was only allowed and contracted by the state. Rents should be affordable for all dwellers. Incomes should not decide about the housing conditions. Under these conditions, the DDR Regime started a major construction program in 1973, which should solve the predominant housing issue - as a social problem - until 1990. During the time when the wall fell, almost 30 years ago, the inner cities were in bad shape - and many newly constructed prefabricated buildings were already in need of refurbishment. Every DDR citizen had the right to dwell in an adequate apartment - this was enshrined in the constitution. But in reality, the housing shortage was still growing and the living conditions were, by far, not as glorious as planned. While the living conditions in the former DDR have already been extensively studied by many scientists, the following work incorporates already existing research results, which prove how the former dwellers experienced grievance in the area of living. In addition to that, those stated results are covered and compared with empirical research information, in order to clarify the source of the error, from an architectural point of view. For the mentioned statements, empirical data was collected in the form of interviews with former residents of the WBS 70 series. These interviews were recorded, transcribed, translated, analysed and finally compared with the previous results. The following sheets present the main cause of dissatisfaction, according to a dramatically lack of living space, which executed impact on the entire social life. The large majority of all subjects was affected by this problem and according to their statements, the vast majority of all East-Berlin residents, experienced similar issues. However, this issue can hardly be traced back to a failure in architectural terms, but much more a failure on political levels. Apart from that, however, positive features emerged as well. Accordingly, this work arrives to the conclusion that interior-architectural situations, very well influence the social well-being of dwellers. With regard to the housing construction series WBS 70, it is clear that a negative impact existed. The inhabitants were very limited in their personal development, which, however, forced them to develop evasive solutions and to rely more on social communication and cooperation. In effect, the limitations of the WBS 70 series, pushed its inhabitants to develop their personality in a thriving way.N/

Characterization of cascadable excitability in a silicon-on-insulator microring

C

Organization of the Drosophila larval visual circuit

Visual systems transduce, process and transmit light-dependent environmental cues. Computation of visual features depends on the types of photoreceptor neurons (PR) present, the organization of the eye and the wiring of the underlying neural circuit. Here, we describe the circuit architecture of the visual system of Drosophila larvae by mapping the synaptic wiring diagram and neurotransmitters. By contacting different targets, the two larval PR-subtypes create parallel circuits potentially underlying the computation of absolute light intensity and temporal light changes already within this first visual processing center. Locally processed visual information then signals via dedicated projection interneurons to higher brain areas including the lateral horn and mushroom body. The stratified structure of the LON suggests common organizational principles with the adult fly and vertebrate visual systems. The complete synaptic wiring diagram of the LON paves the way to understanding how circuits with reduced numerical complexity control wide ranges of behaviors

MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation.

PURPOSE: To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection. METHODS: S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique. RESULTS: Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine. CONCLUSION: Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines

Antimicrobial Photodynamic Coatings Reduce the Microbial Burden on Environmental Surfaces in Public Transportation—A Field Study in Buses

Millions of people use public transportation daily worldwide and frequently touch surfaces, thereby producing a reservoir of microorganisms on surfaces increasing the risk of transmission. Constant occupation makes sufficient cleaning difficult to achieve. Thus, an autonomous, permanent, antimicrobial coating (AMC) could keep down the microbial burden on such surfaces. A photodynamic AMC was applied to frequently touched surfaces in buses. The microbial burden (colony forming units, cfu) was determined weekly and compared to equivalent surfaces in buses without AMC (references). The microbial burden ranged from 0–209 cfu/cm2 on references and from 0–54 cfu/cm2 on AMC. The means were 13.4 ± 29.6 cfu/cm2 on references and 4.5 ± 8.4 cfu/cm2 on AMC (p < 0.001). The difference in microbial burden on AMC and references was almost constant throughout the study. Considering a hygiene benchmark of 5 cfu/cm2, the data yield an absolute risk reduction of 22.6% and a relative risk reduction of 50.7%. In conclusion, photodynamic AMC kept down the microbial burden, reducing the risk of transmission of microorganisms. AMC permanently and autonomously contributes to hygienic conditions on surfaces in public transportation. Photodynamic AMC therefore are suitable for reducing the microbial load and closing hygiene gaps in public transportation

MEK inhibition is a promising therapeutic strategy for MLL-rearranged infant acute lymphoblastic leukemia patients carrying RAS mutations

Acute lymphoblastic leukemia (ALL) in infants is an aggressive malignancy with a poor clinical outcome, and is characterized by translocations of the Mixed Lineage Leukemia (MLL) gene. Previously, we identified RAS mutations in 14-24% of infant ALL patients, and showed that the presence of a RAS mutation decreased the survival chances even further. We hypothesized that targeting the RAS signaling pathway could be a therapeutic strategy for RAS-mutant infant ALL patients. Here we show that the MEK inhibitors Trametinib, Selumetinib and MEK162 severely impair primary RAS-mutant MLL-rearranged infant ALL cells in vitro. While all RAS-mutant samples were sensitive to MEK inhibitors, we found both sensitive and resistant samples among RAS-wildtype cases. We confirmed enhanced RAS pathway signaling in RASmutant samples, but found no apparent downstream over-activation in the wildtype samples. However, we did confirm that MEK inhibitors reduced p-ERK levels, and induced apoptosis in the RAS-mutant MLL-rearranged ALL cells. Finally, we show that MEK inhibition synergistically enhances prednisolone sensitivity,

Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia

Pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) exhibit favorable survival rates. However, for AML and ALL patients carrying KMT2A gene translocations clinical outcome remains unsatisfactory. Key players in KMT2A-fusion-driven leukemogenesis include menin and DOT1L. Recently, menin inhibitors like revumenib have garnered attention for their potential therapeutic efficacy in treating KMT2A-rearranged acute leukemias. However, resistance to menin inhibition poses challenges, and identifying which patients would benefit from revumenib treatment is crucial. Here, we investigated the in vitro response to revumenib in KMT2A-rearranged ALL and AML. While ALL samples show rapid, dose-dependent induction of leukemic cell death, AML responses are much slower and promote myeloid differentiation. Furthermore, we reveal that acquired resistance to revumenib in KMT2A-rearranged ALL cells can occur either through the acquisition of MEN1 mutations or independently of mutations in MEN1. Finally, we demonstrate significant synergy between revumenib and the DOT1L inhibitor pinometostat in KMT2A-rearranged ALL, suggesting that such drug combinations represent a potent therapeutic strategy for these patients. Collectively, our findings underscore the complexity of resistance mechanisms and advocate for precise patient stratification to optimize the use of menin inhibitors in KMT2A-rearranged acute leukemia.</p