The effects of personal protective respirators on human motor, visual, and cognitive skills

In oxygen-deficient or toxic environments in which controlling the hazard is not feasible, workers wear personal protective respirators. Hazard controls include but are not limited to engineering controls, such as ventilation, and substituting less hazardous materials. However, respirator selection and the design of tasks that require respirators are critical issues. Understanding the effects of respirators on human abilities is critical to respirator selection and therefore to the safety and efficiency of workers. This research investigated the effect of respirators on human abilities. A review of the relevant literature was conducted, revealing that respirators can affect physiological, psychological, motor, and visual abilities. However, the effect varies with different types of respirators, environments and task types and difficulty levels. The details of this variance were identified and further investigated through experimentation. The study compared a dust respirator, powered-air purifying respirator and full-facepiece respirator in terms of their effect on fine motor, visual and cognitive tasks. Thirty participants performed the Hand Tool Dexterity test, Motor-Free Visual Perception test (MVPT-3) and Serial Seven test. Each participant performed each task without a respirator and then while wearing each type of respirator. Task completion time and error rate were measured as indicators of performance. Participants also were surveyed regarding respirator comfort, anxiety level, and perceived task difficulty. ANOVA, least significant difference, and least square means analyses showed that none of the respirators significantly affected task completion time. A significant increase was found in the error rate when participants performed the cognitive test while wearing the full-facepiece respirator --Abstract, page iv

Novel therapeutic approach for regulating the susceptibility of epitheliato adenovirus infection

Human Adenoviruses (AdVs) are etiologic agents for respiratory tract, digestive tract, heart, and eye infections. Although most AdV infections are self-resolving, some infections progress to acute respiratory disease with up to 50% mortality, particularly in immunosuppressed people. Except for vaccines for serotypes, 4 and 7, serotypes that are prevalent in the military, no vaccines or therapeutics that specifically prevent or treat AdV infection exist. On the other hand, AdV remains the most common vector system used in gene therapy clinical trials worldwide and several AdV vectors show promise in phase III clinical trials. The majority of AdVs use the coxsackievirus and adenovirus receptor (CAR) as a primary receptor. We have characterized an alternatively spliced eight-exon containing isoform (CAREx8) that localizes at the apical surface of epithelial cells and is responsible for the initiation of apical AdV infection. A cellular scaffold protein named Membrane Associated Guanylate Kinase, WW and PDZ Domain Containing 1 (MAGI-1) directly interacts with and alternatively regulates CAREx8 through the C-terminal PDZ-binding domain. The alternative regulation is due to the interaction with two different domains, namely PDZ1 and PDZ3, within the same molecule (MAGI-1). I hypothesized that cell permeable peptides that target the interaction between MAGI-1 PDZ1 domain and CAREx8 (TAT-PDZ1) would be able to decrease CAREx8 protein levels and prevent AdV infection. On the other hand, peptides that target the interaction between MAGI-1 PDZ3 domain and CAREx8 (TAT-PDZ3) would be able to increase CAREx8 and enhance AdV mediated gene therapy. Decoy peptides that target the assigned domain were synthesized and conjugated to TAT cell permeable peptide to facilitate peptide entry (TAT-PDZ1; TAT-NET1, TAT-E6) or (TAT-PDZ3; TAT-CAREx8-9c, TAT-ESAM). Peptide entry into the polarized epithelia was confirmed by mass spectroscopy and fluorescence microscopy. Treatment with TAT-PDZ1 peptides decreased the cellular levels of CAREx8 and suppressed AdV transduction in MDCK, human airway epithelia (HAE), as well as epithelia from cotton rats, an animal model of AdV pathogenicity. To determine the mechanism of peptide action, CAREx8 localization was tracked by immunofluorescence. Interestingly, TAT-PDZ1 caused nuclear translocation of CAREx8 C-term domain, an effect that was reversed by ADAM17 inhibitor (TIMP3) and ¿-secretase inhibitor (Comp E), implicating the regulated intramembrane proteolysis (RIP) pathway. Immunoprecipitation and direct ligand binding assays showed that ADAM17 interacts specifically with MAGI-1 PDZ2 domain, suggesting that TAT-PDZ1 peptides caused CAREx8 degradation by enhancing the proximity of the substrate (CAREx8) and enzyme (ADAM17). Finally, ADAM17 caused CAREx8 extracellular domain (ECD) shedding that was able to significantly decrease AdV-GFP transduction, indicating a second protective role against AdV entry by the shed ECD of CAREx8. By contrast, TAT-PDZ3 peptides increased the levels of CAREx8 and significantly increased AdV entry and transduction in MDCK, HAE, and cotton rat epithelia. Upon TAT-PDZ3 peptide administration, CAREx8 was localized in vesicular pattern compartments distinct from MAGI-1 and spread throughout the apical trafficking pathway and at the apical surface of the epithelium. Investigation of the trafficking pathway of CAREx8 using Rabs reveal the possibility of CAREx8 is residing within the recycling Endosomal-Golgi pathway. Neither TAT-PDZ1 nor TAT-PDZ3 binding peptides altered epithelium formation, as measured by transepithelial resistance (TER) as well as dextran permeability across the epithelia, indicating the safety of the peptides on epithelial integrity. Moreover, intranasal administration of TAT-PDZ3 peptides increased AdV transduction by 300-500% while TAT-PDZ1 peptides decreased AdV transduction by 80-95% after intrana..

Preparation and polymeric encapsulation of powder mineral pellets for self-healing cement based materials

Using mineral additives and admixtures as self-healing agents in cement-based composites has been extensively researched. However, if the minerals are added directly to the cementitious matrix without any protection, they could immediately react, leading to a decrease in self-healing efficiency with further associated side-effects on the mechanical properties of cementitious composites. Thus, this paper describes the development of coated pellets as a self-healing system in cement based materials. Pan pelletisation was utilised for producing pellets from three different powder minerals as potential healing agents: reactive magnesium oxide (MgO), silica fume and bentonite. Of these materials, two types of developed prototype pellets in addition to another two commercial types of MgO pellets with different pellet sizes were then encapsulated in a polyvinyl alcohol (PVA) based film coating. The PVA coating was evaluated for the apparent solubility in water and in alkaline solution, swelling property, water permeability, dynamic mechanical properties, and shell thickness on pellets. Although PVA coating exhibited a decrease in its mechanical properties in water or in the simulated concrete environment, it retained integrity and stability in both environments. The PVA shell thickness varied from 10 to 50 µm. As the coated pellets partially replaced the natural sand in mortar mixtures, they were characterised in comparison with sand for the particle size distribution, density, porosity, crushing strength and particle shape. Experimental results indicated that the different types of pellets showed higher porosity and lower crushing strength compared to sand. In mortar mixtures, the pellets showed excellent compatibility with minimal influence on the fresh mixture properties and the compressive strength of the hardened specimens. This was accompanied by good distribution inside the concrete matrix. Further investigations on the self-healing performance of these pellets are under way

Planificación de sistemas UMTS mediante sistemas de información geográfica

En esta Tesis Doctoral se lleva a cabo un análisis de las redes celulares de Tercera Generación basadas en WCDMA desde el punto de vista de planificación y estimación de capacidad. En la planificación tradicional debido al excesivo uso de campañas de medidas, esto hace que el coste sea muy elevado. En esta tesis se ha realizado un modelo de planificación de sistemas UMTS mediante sistemas de información geográfica (ARC/INFO) potente que provee una base de datos geográfica adaptable y capaz de hacer todo tipo de tareas sobre esta información utilizando mapas digitales que reflejan el estado real del entorno en el área a planificar. El hecho de elegir el ARC/INFO, un Sistema de Información Geográfica potente para nuestra aplicación de planificación de sistemas celulares, es por sus grandes ventajas y su sencillez de uso sobre sistemas operativos robustas como el Unix. Este modelo de planificación utiliza modelos de propagación que dan buen margen de la predicción de las perdidas de propagación que tienen en cuenta los edificios y las calles del entorno urbano, así los resultados tendrán más precisión a la hora de planificación. La planificación radio en UMTS tiene por finalidad realizar los cálculos de cobertura y capacidad, con objeto de optimizar el despliegue de las estaciones bases y así cumplir los objetivos de calidad de servicio establecidos por el operador. En esta tesis se ha analizado en general los factores más importantes que afectan a la capacidad y en especial se ha estudiado en más detalles el efecto del coeficiente de correlación entre estaciones bases sobre la capacidad de los sistemas UMTS en entornos urbanos.Khalil Hassan Alghamri, M. (2005). Planificación de sistemas UMTS mediante sistemas de información geográfica [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/2902Palanci

The Coxsackievirus and Adenovirus Receptor Has a Short Half-Life in Epithelial Cells

The coxsackievirus and adenovirus receptor (CAR) is an essential cellular protein that is involved in cell adhesion, cell signaling, and viral infection. The 8-exon encoded isoform (CAREx8) resides at the apical surface of polarized epithelia, where it is accessible as a receptor for adenovirus entering the airway lumen. Given its pivotal role in viral infection, it is a target for antiviral strategies. To understand the regulation of CAREx8 and determine the feasibility of receptor down regulation, the half-life of total and apical localized CAREx8 was determined and correlated with adenovirus transduction. Total and apical CAREx8 has a relatively short half-life of approximately 2 h. The half-life of apical CAREx8 correlates well with adenovirus transduction. These results suggest that antiviral strategies that aim to degrade the primary receptor for apical adenovirus infection will be effective within a relatively short time frame after application

Impregnation and encapsulation of lightweight aggregates for self-healing concrete

This study investigated a technique of impregnating potential self-healing agents into lightweight aggregates (LWA) and the self-healing performance of concrete mixed with the impregnated LWA. Lightweight aggregates with a diameter range of 4–8 mm were impregnated with a sodium silicate solution as a potential self-healing agent. Concrete specimens containing the impregnated LWA and control specimens were pre-cracked up to 300 μm crack width at 7 days. Flexural strength recovery and reduction in water sorptivity were examined. After 28 days healing in water, the specimens containing the impregnated LWA showed ∼80% recovery of the pre-cracking strength, which accounts more than five times of the control specimens’ recovery. The capillary water absorption was also significantly improved; the specimens healed with the impregnated LWA showed a 50% reduction in the sorptivity index compared with the control cracked specimens and a very similar response to the control uncracked specimens. The contribution of sodium silicate in producing more calcium silicate hydrate gel was confirmed by characterisation the healing products using X-ray diffraction, Fourier transform spectroscopy, and scanning electron microscopy.Yousef Jameel Foundation through Cambridge Commonwealth, European & International Trust, Engineering and Physical Sciences Research Council (Project Ref. EP/K026631/1 – ‘‘Materials for Life”

Current Approaches for Glioma Gene Therapy and Virotherapy

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in the adult population and it carries a dismal prognosis. Inefficient drug delivery across the blood brain barrier (BBB), an immunosuppressive tumor microenvironment (TME) and development of drug resistance are key barriers to successful glioma treatment. Since gliomas occur through sequential acquisition of genetic alterations, gene therapy, which enables to modification of the genetic make-up of target cells, appears to be a promising approach to overcome the obstacles encountered by current therapeutic strategies. Gene therapy is a rapidly evolving field with the ultimate goal of achieving specific delivery of therapeutic molecules using either viral or non-viral delivery vehicles. Gene therapy can also be used to enhance immune responses to tumor antigens, reprogram the TME aiming at blocking glioma-mediated immunosuppression and normalize angiogenesis. Nano-particles-mediated gene therapy is currently being developed to overcome the BBB for glioma treatment. Another approach to enhance the anti-glioma efficacy is the implementation of viro-immunotherapy using oncolytic viruses, which are immunogenic. Oncolytic viruses kill tumor cells due to cancer cell-specific viral replication, and can also initiate an anti-tumor immunity. However, concerns still remain related to off target effects, and therapeutic and transduction efficiency. In this review, we describe the rationale and strategies as well as advantages and disadvantages of current gene therapy approaches against gliomas in clinical and preclinical studies. This includes different delivery systems comprising of viral, and non-viral delivery platforms along with suicide/prodrug, oncolytic, cytokine, and tumor suppressor-mediated gene therapy approaches. In addition, advances in glioma treatment through BBB-disruptive gene therapy and anti-EGFRvIII/VEGFR gene therapy are also discussed. Finally, we discuss the results of gene therapy-mediated human clinical trials for gliomas. In summary, we highlight the progress, prospects and remaining challenges of gene therapies aiming at broadening our understanding and highlighting the therapeutic arsenal for GBM.Fil: Banerjee, Kaushik. University of Michigan; Estados UnidosFil: Núñez Aguilera, Felipe Javier. Fundación Instituto Leloir; ArgentinaFil: Haase, Santiago. University of Michigan; Estados UnidosFil: McClellan, Brandon L.. University of Michigan; Estados UnidosFil: Faisal, Syed M.. University of Michigan; Estados UnidosFil: Carney, Stephen V.. University of Michigan; Estados UnidosFil: Yu, Jin. University of Michigan; Estados UnidosFil: Alghamri, Mahmoud S.. University of Michigan; Estados UnidosFil: Asad, Antonela Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nicola Candia, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Varela, Maria Luisa. University of Michigan; Estados UnidosFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Lowenstein, Pedro R.. University of Michigan; Estados UnidosFil: Castro, Maria G.. University of Michigan; Estados Unido

Immunotherapy for gliomas: shedding light on progress in preclinical and clinical development

Gliomas are infiltrating brain tumors associated with high morbidity and mortality. Current standard of care includes radiation, chemotherapy and surgical resection. Today, survival rates for malignant glioma patients remain dismal and unchanged for decades. The glioma microenvironment is highly immunosuppressive and consequently this has motivated the development of immunotherapies for counteracting this condition, enabling the immune cells within the tumor microenvironment to react against this tumor.Areas covered: The authors discuss immunotherapeutic strategies for glioma in phase-I/II clinical trials and illuminate their mechanisms of action, limitations and key challenges. They also examine promising approaches under preclinical development.Expert opinion: In the last decade there has been an expansion in immune-mediated anti-cancer therapies. In the glioma field, sophisticated strategies have been successfully implemented in preclinical models. Unfortunately, clinical trials have not yet yielded consistent results for glioma patients. This could be attributed to our limited understanding of the complex immune cell infiltration and its interaction with the tumor cells, the selected time for treatment, the combination with other therapies and the route of administration of the agent. Applying these modalities to treat malignant glioma is challenging, but many new alternatives are emerging to by-pass these hurdles.Fil: Garcia Fabiani, Maria Belen. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ventosa, Maria. University of Michigan; Estados UnidosFil: Comba, Andrea. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nicola Candia, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Alghamri, Mahmoud S.. University of Michigan; Estados UnidosFil: Kadiyala, Padma. University of Michigan; Estados UnidosFil: Carney, Stephen. University of Michigan; Estados UnidosFil: Faisal, Syed M.. University of Michigan; Estados UnidosFil: Schwendeman, Anna. University of Michigan; Estados UnidosFil: Moon, James J.. University of Michigan; Estados UnidosFil: Scheetz, Lindsay. University of Michigan; Estados UnidosFil: Lahann, Joerg. University of Michigan; Estados UnidosFil: Mauser, Ava. University of Michigan; Estados UnidosFil: Lowenstein, Pedro R.. University of Michigan; Estados UnidosFil: Castro, Maria Gabriela. University of Michigan; Estados Unido

Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies

High grade gliomas are malignant brain tumors that arise in the central nervous system, in patients of all ages. Currently, the standard of care, entailing surgery and chemo radiation, exhibits a survival rate of 14-17 months. Thus, there is an urgent need to develop new therapeutic strategies for these malignant brain tumors. Currently, immunotherapies represent an appealing approach to treat malignant gliomas, as the pre-clinical data has been encouraging. However, the translation of the discoveries from the bench to the bedside has not been as successful as with other types of cancer, and no long-lasting clinical benefits have been observed for glioma patients treated with immune-mediated therapies so far. This review aims to discuss our current knowledge about gliomas, their molecular particularities and the impact on the tumor immune microenvironment. Also, we discuss several murine models used to study these therapies pre-clinically and how the model selection can impact the outcomes of the approaches to be tested. Finally, we present different immunotherapy strategies being employed in clinical trials for glioma and the newest developments intended to harness the immune system against these incurable brain tumors.Fil: Garcia Fabiani, Maria Belen. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Haase, Santiago. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Comba, Andrea. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carney, Stephen. University of Michigan; Estados UnidosFil: McClellan, Brandon. University of Michigan; Estados UnidosFil: Banerjee, Kaushik. University of Michigan; Estados UnidosFil: Alghamri, Mahmoud S.. University of Michigan; Estados UnidosFil: Syed, Faisal. University of Michigan; Estados UnidosFil: Kadiyala, Padma. University of Michigan; Estados UnidosFil: Nuñez, Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Asad, Antonela Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: González, Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Aikins, Marisa E.. University of Michigan; Estados UnidosFil: Schwendeman, Anna. University of Michigan; Estados UnidosFil: Moon, James J.. University of Michigan; Estados UnidosFil: Lowenstein, Pedro R.. University of Michigan; Estados UnidosFil: Castro, Maria G.. University of Michigan; Estados Unido

Systemic Delivery of an Adjuvant CXCR4-CXCL12 Signaling Inhibitor Encapsulated in Synthetic Protein Nanoparticles for Glioma Immunotherapy

Glioblastoma (GBM) is an aggressive primary brain cancer, with a 5 year survival of ∼5%. Challenges that hamper GBM therapeutic efficacy include (i) tumor heterogeneity, (ii) treatment resistance, (iii) immunosuppressive tumor microenvironment (TME), and (iv) the blood-brain barrier (BBB). The C-X-C motif chemokine ligand-12/C-X-C motif chemokine receptor-4 (CXCL12/CXCR4) signaling pathway is activated in GBM and is associated with tumor progression. Although the CXCR4 antagonist (AMD3100) has been proposed as an attractive anti-GBM therapeutic target, it has poor pharmacokinetic properties, and unfavorable bioavailability has hampered its clinical implementation. Thus, we developed synthetic protein nanoparticles (SPNPs) coated with the transcytotic peptide iRGD (AMD3100-SPNPs) to target the CXCL2/CXCR4 pathway in GBM via systemic delivery. We showed that AMD3100-SPNPs block CXCL12/CXCR4 signaling in three mouse and human GBM cell cultures in vitro and in a GBM mouse model in vivo. This results in (i) inhibition of GBM proliferation, (ii) reduced infiltration of CXCR4+ monocytic myeloid-derived suppressor cells (M-MDSCs) into the TME, (iii) restoration of BBB integrity, and (iv) induction of immunogenic cell death (ICD), sensitizing the tumor to radiotherapy and leading to anti-GBM immunity. Additionally, we showed that combining AMD3100-SPNPs with radiation led to long-term survival, with ∼60% of GBM tumor-bearing mice remaining tumor free after rechallenging with a second GBM in the contralateral hemisphere. This was due to a sustained anti-GBM immunological memory response that prevented tumor recurrence without additional treatment. In view of the potent ICD induction and reprogrammed tumor microenvironment, this SPNP-mediated strategy has a significant clinical translation applicability.Fil: Alghamri, Mahmoud S.. University Of Michigan Medical School; Estados UnidosFil: Banerjee, Kaushik. University Of Michigan Medical School; Estados UnidosFil: Mujeeb, Anzar A.. University Of Michigan Medical School; Estados UnidosFil: Mauser, Ava. University of Michigan; Estados UnidosFil: Taher, Ayman. University Of Michigan Medical School; Estados UnidosFil: Thalla, Rohit. University Of Michigan Medical School; Estados UnidosFil: McClellan, Brandon L.. University Of Michigan Medical School; Estados UnidosFil: Varela, Maria L.. University Of Michigan Medical School; Estados UnidosFil: Stamatovic, Svetlana M.. University Of Michigan Medical School; Estados UnidosFil: Martinez Revollar, Gabriela. University Of Michigan Medical School; Estados UnidosFil: Andjelkovic, Anuska V.. University Of Michigan Medical School; Estados UnidosFil: Gregory, Jason V.. University of Michigan; Estados UnidosFil: Kadiyala, Padma. University Of Michigan Medical School; Estados UnidosFil: Calinescu, Alexandra. University Of Michigan Medical School; Estados UnidosFil: Jiménez, Jennifer A.. University of Michigan; Estados UnidosFil: Apfelbaum, April A.. University of Michigan; Estados UnidosFil: Lawlor, Elizabeth R.. University of Washington; Estados UnidosFil: Carney, Stephen. University of Michigan; Estados UnidosFil: Comba, Andrea. University Of Michigan Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Faisal, Syed Mohd. University Of Michigan Medical School; Estados UnidosFil: Barissi, Marcus. University Of Michigan Medical School; Estados UnidosFil: Edwards, Marta B.. University Of Michigan Medical School; Estados UnidosFil: Appelman, Henry. University Of Michigan Medical School; Estados UnidosFil: Sun, Yilun. Case Western Reserve University; Estados UnidosFil: Gan, Jingyao. University of Michigan; Estados UnidosFil: Ackermann, Rose. University of Michigan; Estados UnidosFil: Schwendeman, Anna. University of Michigan; Estados UnidosFil: Candolfi, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Olin, Michael R.. University of Minnesota; Estados UnidosFil: Lahann, Joerg. University of Michigan; Estados UnidosFil: Lowenstein, Pedro R.. University of Michigan; Estados UnidosFil: Castro, Maria G.. University of Michigan; Estados Unido