Restoration of the colonial past in Argentina : projects by Mario J. Buschiazzo for the intervention of National Historical Monuments (1937-1947)

This research, as part of heritage studies and aims to analyze the relations between heritage assessment and intervention in the context of the reassessment of colonial architecture during the foundational phase of the heritage field in Argentina (1937-1947). With that purpose, this work focuses in analyzing National Historic Monuments from the Colonial period located in the Center, Parana River Coastline and Northwest of Argentina and their interventions considering the projects developed by Mario J. Buschiazzo. Towards the end of 1930, Argentina began a systematic patrimonialization process that consolidated the colonial architecture as a reference of national identity. After a long process initiated, in the architectural field by the neocolonial movement debates, it was time to deal with preservation architecture. Once the political administrative structure to safeguard and protect heritage had been established through the creation of the National Commission of Museums, Monuments and Historical Sites (CNMMyLH in Spanish) the next mandatory step was to decide how to preserve the recently nominated historic monuments. Mario Buschiazzo a reference from history of colonial architecture in America, was in charge of designing the interventions for their re-assessment. Without local experience, with the colonial heritage in a heterogeneous conservation state and in an international context of dissociated criteria between theory and practice, the challenge was raised. Bibliography points to the fact that Argentinian historical studies have assessed the colonial architecture based on a stylistic and synchronic approach, without considering the interventions that had taken place in these buildings. However, the current outlook of many of them is the result of the restorations implemented during the '40ties. Moreover, the approach that summarizes this period prevails in the iconic reconstruction examples from the Independence House in Tucuman and the Town Council from Buenos Aires. Taking this into account, the general purpose of this thesis is to increase the previous knowledge considering variability and new dimensions of analysis. Thus, the proposal is to deepen the analysis and to add specificity by studying the Town Council of Salta, the Posta of Sinsacate, the Uriburu House and the San Francisco Convent and Temple. These examples reflect restorations of monumental and modest architectural, with different valuation, acknowledgement and conservation state that allows to explore the relationship between the theoretical and the practical problems that converge at historic monuments during the foundational period of the CNMMyLH with an integral approach including the context, documental and technical-conservative dimensions.Fil: Herr, Carola Ingrid. Universidad de Buenos Aires. Facultad de Arquitectura, Diseño y Urbanismo. Buenos Aires, ArgentinaLa presente investigación se inscribe en el ámbito de los estudios patrimoniales y tiene como objetivo problematizar la relación existente entre la valoración y la intervención patrimonial en el escenario de revalorización de la arquitectura colonial durante la etapa fundacional del campo patrimonial (1937-1947). Para ello se centra en el estudio de los Monumentos Históricos Nacionales, correspondientes al período colonial del Centro, Litoral y Noroeste argentino, y de las intervenciones de los que fueron objeto, conforme a los proyectos delineados por el arquitecto Mario J. Buschiazzo. Argentina comenzó, hacia fines de la década de 1930, un proceso sistemático de patrimonialización y "activó" como referentes patrimoniales a obras del período colonial. Tras una dilatada espera, iniciada en el campo arquitectónico con los debates del movimiento neocolonial, había llegado el turno de dar respuesta a la problemática de la preservación arquitectónica. Establecida la estructura político-administrativa para la tutela y protección patrimonial, mediante la creación de la Comisión Nacional de Museos, de Monumentos y de Lugares Históricos (CNMMyLH), el paso siguiente, y casi obligado, consistió en decidir "cómo" preservar a los recientemente catalogados Monumentos Histórico-Nacionales (MHN). Mario J. Buschiazzo (MJB), referente de la historia de la arquitectura colonial americana, fue quien debió proyectar las intervenciones para su revaloración. Sin experiencias previas en el ámbito local, con una herencia colonial heterogénea en su estado de conservación y frente un clima de desacuerdos entre la teoría y la praxis en el ámbito internacional, el desafió estaba planteado. Los antecedentes bibliográficos permiten advertir que la historiografía argentina se focalizó en estudiar aspectos relativos a la valoración de la arquitectura producida en la etapa colonial, desde aproximaciones estilísticas y sincrónicas, con mínima o nula consideración de las intervenciones que acontecieron en ellas. Sin embargo, la imagen actual de muchos de los MHN es producto de las restauraciones practicadas durante la década de 1940. Asimismo, prevalece un enfoque que sintetiza lo actuado en dicho período a partir de explicitar las reconstrucciones llevadas a cabo en obras paradigmáticas tales como la Casa Histórica de la Independencia, en Tucumán, y el Cabildo de Buenos Aires. Bajo estas consideraciones, el propósito general de la tesis es realizar un aporte al conocimiento del campo historiográfico y ampliar la comprensión de lo actuado, incorporando variabilidad y nuevas dimensiones de análisis a los estudios previos. Así, se propone profundizar el análisis e incrementar especificidad a partir del estudio del Cabildo de Salta, la Posta de Sinsacate, la Casa de los Uriburu y el Convento y Templo de San Francisco. Estos reflejan restauraciones realizadas en MH de escala modesta y monumental, con diversos grados de valoración, reconocimiento y estado de conservación para abordar la interrelación entre el problema teórico y el práctico que confluyen en los MHN, durante la etapa fundacional de la CNMMyLH, desde un enfoque integral que incluye su dimensión contextual, documental y técnico-conservativa

Restoration of colonial heritage: Criteria and intervention techniques applied in the first half of the 20th Century in Argentina

La arquitectura del período colonial constituyó el corpus principal de patrimonialización durante el período 1937-1947, cuando se inició la gestión patrimonial en Argentina. Constituida mayoritariamente por tecnologías de construcción con tierra, su valoración se centró en destacar los atributos morfológicos expresivos de estas edificaciones, mientras la dimensión material tuvo escasa consideración. Esta perspectiva también se replicó en la práctica de la restauración en tanto la materialidad y las técnicas fueron utilizadas como instrumentos subordinados a una determinada expresión formal. El presente artículo propone analizar los criterios, principiosy técnicas de intervención implementadas en monumentos arquitectónicos del periodo colonial construidos con tecnologías de tierra durante la etapa fundacional, atendiendo a las relaciones establecidas entre forma y materia. Para ello se presenta un análisis de cuatro casos de estudio que conjuga diversas estrategias teórico-metodológicas. Por un lado, el análisis historiográfico que permite contextualizar la gestión patrimonial y el registro de la arquitectura colonial en el período de estudio, en términos de alteración, conservación y materialidad. Por otro, la caracterización y el análisis de las intervenciones, combinando el análisis historiográfico y el trabajo de campo.The architecture of the colonial period constituted the main corpus of patrimonialisation during the period 1937-1947, when heritage polices began in Argentina. Built mainly of earth construction techniques, its assessment focused on highlighting the morphological and expressive attributes of these buildings while the material dimension was barely considered. This approach was also replicated in the restoration practice, as materiality and techniques were used as subordinate instruments of a specific formal expression. This article proposes to analyze the intervention criteria, principles and techniques implemented in architectural monuments of the colonial period built with earthen technologies during the foundational phase, regarding the relationship established between form and matter. An analysis of four case studies that combines different theoretical and methodological strategies is presented for this purpose. On the one hand, the historiographical analysis to contextualize heritage management and the records of colonial architecture at that period, in terms of alteration, conservation and materiality. On the other, the characterization and analysis of the interventions, combining historiographical analysis with the fieldwork.Fil: Herr, Carola Ingrid. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Estudios Sobre Patrimonio y Ambiente (cepya) ; Escuela de Arte y Patrimonio  ; Universidad Nacional de San Martin

c-Jun-Dependent CD95-L Expression Is a Rate-Limiting Step in the Induction of Apoptosis by Alkylating Agents

Mouse 3T3 fibroblasts derived from fetuses lacking c-Jun were used to define an essential role of c-Jun, a main component of the transcription factor AP-1, in the cellular response to the alkylating agent methyl methanesulfonate (MMS). MMS represents the most potent and selective activator of the stress-induced kinases JNK/SAPK and p38, resulting in very efficient induction of c-Jun hyperphosphorylation and c-jun transcription. This agent induced apoptosis with high efficiency in wild-type cells but not in c-jun(−/−) cells. Resistance to apoptosis was accompanied by impaired expression of CD95 ligand (CD95-L), a well-known inducer of apoptosis. The addition of recombinant CD95-L restored apoptosis sensitivity in c-jun(−/−) fibroblasts. MMS-induced apoptosis in wild-type fibroblasts or human lymphocytes was strongly reduced by neutralizing CD95-L antibodies or transdominant negative FADD, confirming the importance of CD95 signalling in MMS-induced apoptosis. The loss-of-function approach in fibroblasts allowed the identification and dissection of c-Jun-dependent and -independent processes upstream or downstream of CD95 activation. We have found that c-Jun can act as a proapoptotic regulator in cells exposed to DNA damage via induction of CD95-L. Once activated, CD95-induced death signalling is not affected by the loss of c-Jun, demonstrating that only the initiation and not the execution of stress-induced apoptosis depends on c-Jun

A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

Development of small molecule NUDT22 inhibitors for uses in cancer

Here, we present the characterisation of the so-far-unstudied NUDIX hydrolase family member NUDT22. We previously identified the unique hydrolase activity of NUDT22 towards UDP-glucose from a family-wide biochemical substrate screen. UDP-glucose hydrolysis was found to result in the production of uridine monophosphate (UMP) and glucose 1-phosphate (G-1-P). We furthermore solved the first crystal structure of NUDT22 in complex with its substrate UDP-glucose [1]. Our mechanistic studies revealed increased replication stress in NUDT22-deficient cells that could be rescued by nucleoside supplementation. We therefore propose the discovery of a novel NUDT22-mediated pyrimidine salvage pathway. Increased replication rates resulting in replication stress is a hallmark of cancer cells, and NUDT22 gene expression alterations are present in several cancer tissues, which makes NUDT22 an interesting new target for the development of small molecule inhibitors for uses in cancer. We employed our NUDT22 crystal structure to perform an in silico docking screen on available small molecule libraries to identify starting points for the development of first-in-class NUDT22 inhibitors. Chemically optimised NUDT22 inhibitors are currently being validated in biochemical assays and cellular target engagement assays, and their cellular activity is being assessed in vitro

Establishment of Tumor Treating Fields Combined With Mild Hyperthermia as Novel Supporting Therapy for Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with poor prognosis and limited therapeutic options. Alternating electrical fields with low intensity called “Tumor Treating Fields” (TTFields) are a new, non-invasive approach with almost no side effects and phase 3 trials are ongoing in advanced PDAC. We evaluated TTFields in combination with mild hyperthermia. Three established human PDAC cell lines and an immortalized pancreatic duct cell line were treated with TTFields and hyperthermia at 38.5°C, followed by microscopy, assays for MTT, migration, colony and sphere formation, RT-qPCR, FACS, Western blot, microarray and bioinformatics, and in silico analysis using the online databases GSEA, KEGG, Cytoscape-String, and Kaplan-Meier Plotter. Whereas TTFields and hyperthermia alone had weak effects, their combination strongly inhibited the viability of malignant, but not those of nonmalignant cells. Progression features and the cell cycle were impaired, and autophagy was induced. The identified target genes were key players in autophagy, the cell cycle and DNA repair. The expression profiles of part of these target genes were significantly involved in the survival of PDAC patients. In conclusion, the combination of TTFields with mild hyperthermia results in greater efficacy without increased toxicity and could be easily clinically approved as supporting therapy

A multilaboratory comparison of calibration accuracy and the performance of external references in analytical ultracentrifugation.

Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies

Search for direct top squark pair production in events with a Higgs or Z boson, and missing transverse momentum in √s=13 TeV pp collisions with the ATLAS detector

A search for direct top squark pair production resulting in events with either a same-flavour opposite-sign dilepton pair with invariant mass compatible with a Z boson or a pair of jets compatible with a Standard Model (SM) Higgs boson (h) is presented. Requirements on the missing transverse momentum, together with additional selections on leptons, jets, jets identified as originating from b-quarks are imposed to target the other decay products of the top squark pair. The analysis is performed using proton-proton collision data at √s=13 TeV collected with the ATLAS detector at the LHC in 2015–2016, corresponding to an integrated luminosity of 36.1 fb−1. No excess is observed in the data with respect to the SM predictions. The results are interpreted in two sets of models. In the first set, direct production of pairs of lighter top squarks (t~1) with long decay chains involving Z or Higgs bosons is considered. The second set includes direct pair production of the heavier top squark pairs (t~2) decaying via t~2→Zt~1 or t~2→ht~1. The results exclude at 95% confidence level t~2 and t~1 masses up to about 800 GeV, extending the exclusion region of supersymmetric parameter space covered by previous LHC searches