Modulation of immune responses using adjuvants to facilitate therapeutic vaccination

Publsher's version (útgefin grein)Therapeutic vaccination offers great promise as an intervention for a diversity of infectious and non-infectious conditions. Given that most chronic health conditions are thought to have an immune component, vaccination can at least in principle be proposed as a therapeutic strategy. Understanding the nature of protective immunity is of vital importance, and the progress made in recent years in defining the nature of pathological and protective immunity for a range of diseases has provided an impetus to devise strategies to promote such responses in a targeted manner. However, in many cases, limited progress has been made in clinical adoption of such approaches. This in part results from a lack of safe and effective vaccine adjuvants that can be used to promote protective immunity and/or reduce deleterious immune responses. Although somewhat simplistic, it is possible to divide therapeutic vaccine approaches into those targeting conditions where antibody responses can mediate protection and those where the principal focus is the promotion of effector and memory cellular immunity or the reduction of damaging cellular immune responses as in the case of autoimmune diseases. Clearly, in all cases of antigen-specific immunotherapy, the identification of protective antigens is a vital first step. There are many challenges to developing therapeutic vaccines beyond those associated with prophylactic diseases including the ongoing immune responses in patients, patient heterogeneity, and diversity in the type and stage of disease. If reproducible biomarkers can be defined, these could allow earlier diagnosis and intervention and likely increase therapeutic vaccine efficacy. Current immunomodulatory approaches related to adoptive cell transfers or passive antibody therapy are showing great promise, but these are outside the scope of this review which will focus on the potential for adjuvanted therapeutic active vaccination strategies.This article/publication is based upon work from COST Action CA16231 ENOVA (European Network of Vaccine Adjuvants), supported by COST (European Cooperation in Science and Technology—www.cost.eu).Peer Reviewe

Greenhouse gas emissions from concrete can be reduced by using mix proportions, geometric aspects, and age as design factors

With increased awareness of the emissions of greenhouse gases (GHGs) and the significant contribution from the cement industry, research efforts are being advanced to reduce the impacts associated with concrete production and consumption. A variety of methods have been proposed, one of the most common being the replacement of cement as a binder in concrete with supplementary cementitious materials, such as fly ash (FA), which can have lower environmental effects. The use of FA can change the kinetics of the hydration reactions and, consequently, modify the evolution of the concrete strength over time. Yet the influence of designing structural elements to obtain the required strength at later ages has not been examined in terms of their influence on global warming potential (GWP) of concrete. This research investigates the influence of design age, in addition to mix proportions and geometric aspects, on the GWP associated with making beams, columns, and a concrete building frame. Findings suggest that while the GWP for beams is not highly dependent on concrete mixture strength, the GWP for columns is dependent on strength, thus the influence of required strength at later ages influences GWP of making columns more so than beams. For the concrete frame analyzed, a potential 45% reduction in GWP, depending on mix proportions and design age, was found. Using the findings from this research, the GWP associated with production of concrete in California could be reduced by approximately 1.8 million metric tons of CO2-eq emissions, equivalent to approximately 2% of all industrial GHG emissions in California

A starfish robot based on soft and smart modular structure (SMS) actuated by SMA wires

This paper describes the design, fabrication and locomotion of a starfish robot whose locomotion principle is derived from a starfish. The starfish robot has a number of tentacles or arms extending from its central body in the form of a disk, like the topology of a real starfish. The arm, which is a soft and composite structure (which we call the smart modular structure (SMS)) generating a planar reciprocal motion with a high speed of response upon the actuation provided by the shape memory alloy (SMA) wires, is fabricated from soft and smart materials. Based on the variation in the resistance of the SMA wires during their heating, an adaptive regulation (AR) heating strategy is proposed to (i) avoid overheating of the SMA wires, (ii) provide bending range control and (iii) achieve a high speed of response favorable to successfully propelling the starfish robot. Using a finite - segment method, a thermal dynamic model of the SMS is established to describe its thermal behavior under the AR and a constant heating strategy. A starfish robot with five SMS tentacles was tested with different control parameters to optimize its locomotion speed. As demonstrated in the accompanying video file, the robot successfully propelled in semi-submerged and underwater environments show its locomotion ability in the multi-media, like a real starfish. The propulsion speed of the starfish robot is at least an order of magnitude higher than that of those reported in the literature-thanks to the SMS controlled with the AR strategy

Malondialdehyde, Antioxidant Enzymes, and Renal Tubular Functions in Children with Iron Deficiency or Iron-Deficiency Anemia

We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-beta-d-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants < 2 years, children 3-9 years, and adolescents 10-15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen