Tolerance and autoimmunity: novel therapeutic approaches

La función primaria del sistema inmune es resguardar al individuo de los patógenos potencialmente dañinos que invaden el medio ambiente en el cual nos desarrollamos. Este cuenta con dos grandes ramas, la inmunidad innata y la adaptativa, ambas con la propiedad de diferenciar lo peligroso de aquello inofensivo. Estos procesos se hallan regulados por mecanismos homeostáticos que constituyen la tolerancia inmunológica, a los fines de limitar aquellos procesos prolongados y silenciar los potencialmente autoagresivos. Ante la falla de estos mecanismos de control, surgen las enfermedades autoinmunes. Avances en el conocimiento de la fisiopatología de estas entidades, han abierto un nuevo capítulo en el terreno de la inmunofarmacología. Su prometedor potencial actualmente nos ofrece novedosas herramientas terapéuticas para controlar y atenuar el daño causado por este tipo de respuestas. No obstante, debe continuarse la investigación en el campo de los agentes biológicos, ya que ninguno de ellos se encuentra libre de inconvenientes. Seguramente, futuros hallazgos se concretarán en futuros aciertos. Y los aciertos, en Medicina, equivalen a esperanza.The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components. Failure to silence self-reactive T and B cells results in the generation of autoimmune disease. Recent advances in our knowledge of these pathological entities have opened a new chapter in the pharmacology of the immune system. Its promising potential currently offers new therapeutic agents to control and attenuate pathological tissue damage. Nevertheless, further research regarding these biologic agents is required, since they are not free from inconveniences. It is without question that upcoming findings in this field will instill hope into the quest for the “magic bullet”.Fil: Ciliberti, Esteban. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Carambia, Leandro. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cavallin, Sebastian. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas; ArgentinaFil: Cerda, Osvaldo L.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Poderoso, Juan J.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Bridging the gap between industry and synchrotron: Operando study at 30 bar over 300 h during Fischer-Tropsch synthesis

In order to reduce CO$_{2}$ emissions, it is necessary to substitute fossil fuels with renewable energy using CO$_{2}$ as a carbon feedstock. An attractive route for synthetic fuel production is the Fe- or Co-catalysed Fischer–Tropsch process. A profound knowledge of the catalyst deactivation phenomena under industrial conditions is crucial for the process optimisation. In this study, we followed the structural changes of a Co–Ni–Re/γ-Al$_{2}$O$_{3}$ catalyst for >300 hours at 30 bar and 250 °C during the Fischer–Tropsch synthesis operando at a synchrotron radiation facility. The advanced setup built for operando X-ray diffraction and X-ray absorption spectroscopy allows simultaneous and robust monitoring of the catalytic activity even over 300 h time on stream. We found three activity regimes for the Co–Ni–Re/γ-Al$_{2}$O$_{3}$ catalyst during 310 h of operation. Fast decline in activity was observed during the initiation phase in the first hours of operation due to liquid film formation (mass transport limitations). Furthermore, solid state reactions and carbon depositions were found while continuing the exposure of the catalyst to harsh temperature conditions of 250 °C. By using this advanced setup, we bridged the gap between industrially oriented catalysts and fundamental studies at synchrotron radiation facilities, opening up new possibilities for operando characterisation of industrial processes that rely on conditions of up to 450 °C and 50 bar

Photovoltaics- and Battery-Based Power Network as Sustainable Source of Electric Power

With the rise in the utilization of free fuel energy sources, namely solar and wind, across the globe, it has become necessary to study and implement models of a sustainable power network. This paper focuses on the design of a conceptual power network based on photovoltaics (PV) for power generation and lithium-ion batteries for storage. The power system showcases the various metrics that are involved in a grid-tied PV- and battery-based power network. It also encompasses the various design parameters and sizing considerations to design and conceptualize such a power network. The model focuses on the importance of the conservation of power by avoiding wastage of generated power through inverter sizing and design considerations. Finally, an economic and feasibility analysis is carried out to showcase the economic viability of the PV- and battery-based power network in today’s alternating current (AC)-based grid

Polymeric Nanohybrids as a New Class of Therapeutic Biotransporters

This is the peer reviewed version of the following article: Macromol Chem Phys. 2016 Jun; 217(11): 1245–1259., which has been published in final form at http://doi.org/10.1002/macp.201500464. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.A possible solution to enhance existing drug and gene therapies is to develop hybrid nanocarriers capable of delivering therapeutic agents in a controlled and targeted manner. This goal can be achieved by designing nanohybrid systems, which combine organic or inorganic nanomaterials with biomacromolecules into a single composite. The unique combination of properties along with their facile fabrication enables the design of smart carriers for both drug and gene delivery. These hybrids can be further modified with cell targeting motifs to enhance their biological interactivity. In this Talents and Trends article, an overview of emerging nanohybrid-based technologies will be provided to highlight their potential use as innovative platforms for improved cancer therapies and new strategies in regenerative medicine. The clinical relevance of these systems will be reviewed to define the current challenges which still need to be addressed to allow these therapies to move from bench to bedside

Soft Web-Based Continuum Robot Grippers

We discuss the potential of soft webs to enhance robotic grasping. Specifically, we explore a novel combination of compliant continuum digits interspersed with a flexible material. The resulting webbed structure offers the potential for new modes of robust and adaptive object grasping. We introduce and describe two webbed grippers featuring alternate modes of actuation: pneumatic muscles and remotely actuated tendons. Experiments with the grippers demonstrate their ability to gently capture small, fragile, and non-cooperative objects

The aryl hydrocarbon receptor in liver inflammation

The aryl hydrocarbon receptor (AHR) is a ubiquitously expressed ligand-activated transcription factor with multifaceted physiological functions. In the immune system, AHR has been unequivocally identified as a key regulatory factor that can integrate environmental, dietary, or microbial signals into innate and adaptive immune responses. Correspondingly, AHR activity seems to be most important at barrier organs, such as the gut, skin, and lung. The liver is likewise prominently exposed to gut-derived dietary or microbial AHR ligands and, moreover, generates plenty of AHR ligands itself. Yet, surprisingly little is known about the role of AHR in the regulation of hepatic immune responses, which are normally biased towards tolerance, preventing harmful inflammation in response to innocuous stimuli. In this review, we summarize the current knowledge about the role of AHR in hepatic immune responses in the healthy liver as well as in inflammatory liver disease. Moreover, we discuss AHR as a potential therapeutic target in hepatic disorders, including autoimmune liver disease, liver fibrosis, and liver cancer

Indirect IRI estimation through smart tyre technology

In the last decades smart tyre technology has generated growing interest towards different fields of application. The main reason lies in the opportunity to turn passive elements like tyre into active sensors. Moreover, being the tyre a crucial element for vehicle dynamics and the only vehicle part directly in contact with the road, it provides the best monitoring location of road and vehicle interaction. This paper demonstrates how smart tyres can provide information about road surface. In particular, the work investigates how a vehicle fitted with smart tyres can enhance the monitoring of road conditions through the estimation of road unevenness, which is one of the most critical aspects for vehicle ride comfort. The presented solution represents a flexible and widely usable system capable of providing an indication of the IRI index (International Roughness Index), the most worldwide used road unevenness index. The solution is based on a generic vehicle fitted with four smart tyres, each equipped with an accelerometer sensor