pMHC affinity controls duration of CD8+ T cell-DC interactions and imprints timing of effector differentiation versus expansion.

During adaptive immune responses, CD8(+) T cells with low TCR affinities are released early into the circulation before high-affinity clones become dominant at later time points. How functional avidity maturation is orchestrated in lymphoid tissue and how low-affinity cells contribute to host protection remains unclear. In this study, we used intravital imaging of reactive lymph nodes (LNs) to show that T cells rapidly attached to dendritic cells irrespective of TCR affinity, whereas one day later, the duration of these stable interactions ceased progressively with lowering peptide major histocompatibility complex (pMHC) affinity. This correlated inversely BATF (basic leucine zipper transcription factor, ATF-like) and IRF4 (interferon-regulated factor 4) induction and timing of effector differentiation, as low affinity-primed T cells acquired cytotoxic activity earlier than high affinity-primed ones. After activation, low-affinity effector CD8(+) T cells accumulated at efferent lymphatic vessels for egress, whereas high affinity-stimulated CD8(+) T cells moved to interfollicular regions in a CXCR3-dependent manner for sustained pMHC stimulation and prolonged expansion. The early release of low-affinity effector T cells led to rapid target cell elimination outside reactive LNs. Our data provide a model for affinity-dependent spatiotemporal orchestration of CD8(+) T cell activation inside LNs leading to functional avidity maturation and uncover a role for low-affinity effector T cells during early microbial containment

Valutazione ecografica degli indici di resistività (RI) e di pulsatilità (PI) delle arterie oculari e della biometria oculare nei cani affetti da Leishmaniosi

Canine leishmaniosis is a protozoan disease endemic in the Mediterranean area, caused by Leishmania infantum. It is a chronic and severe systemic disease with various manifestation, one of these being ocular lesions. Pulsed Wave Doppler ultrasonography provides indirect information about ocular and orbital vascular flow resistance through the measurements of the Resistive (RI) e and the Pulsatility (PI) indices. The main purposes of the present study were to evaluate the ophthalmic and ciliary artery resistance and to determine the prevalence and type of ocular lesions in a population of dogs naturally infected by Leishmania infantum, before and after medical therapy. 18 dogs naturally infected by Leishmania infantum and 15 healthy dogs as a control group were included in this prospective clinical study. The results showed that ocular flow resistance was significantly higher in the sick dogs compared to the control group and that ocular and periocular tissues were affected in 83% of dogs with systemic Leishmaniasis. The ocular lesions improved or completely resolved and mean PI returned within the reference limits following the therapy, on the contrary, the mean RI remained high in dogs who have undergone therapy. Microcirculatory involvement is well recognised in canine Leishmaniasis, assessment of vascular ocular RI and PI could be a useful tool for assessing disease activity and for monitoring response to treatment

Tunnel shotcrete lining for hydroelectric projects in British Columbia

In British Columbia (BC), Canada, the primary source of power supply is hydroelectricity. The BC government, through its crown corporation, BC Hydro, has been working with private companies to provide sustainable and renewable energy. Private companies are building hydroelectric projects throughout the province of BC. Innergex has been constructing three hydroelectric projects; two are in the Upper Lilllooet area, which is about 250 km north of Vancouver and 80km north of Whistler and the third is in the Big Silver area, which is about 250 km east of Vancouver and 50 km north of Harrison Lake. All of these tunnels are hard rock and have been constructed by the drill and blast method. At the beginning of the projects, dry-mix shotcrete was applied based on the contractor’s previous underground project experience. Wet-mix shotcrete was subsequently introduced as a trial method. The contractor was impressed with its productivity and performance and consequently adopted it as the primary shotcrete placement method. Dry-mix steel fiber reinforced shotcrete continued to be used for special ground conditions. The construction schedule was reduced significantly by using wet-mix shotcrete, with resultant substantial cost savings. The wet-mix shotcrete was initially reinforced with wire mesh and hand-applied. Shortly after, the tunnel lining method was changed to the use of robotic sprayed macrosynthetic fiber reinforced wet-mix shotcrete. A silica fume modified shotcrete mixture was designed and trial shot. Tests results met the project specification requirements for tunnel construction. The wet-mix macrosynthetic fiber reinforced shotcrete was placed, since July 2013, using pre-bagged materials supplied from Vancouver and mixed on site. Later, the contractor set up a dry-batch concrete batch plant on site and started batching shotcrete using local aggregates. The shotcrete mixture was qualified for use on the project by testing for compressive strength, boiled absorption and volume of permeable voids, and flexural toughness based on use of the round determinate panel to ASTM C1550. The effect on shotcrete performance of different addition rates of alkali-free accelerator was tested in trials. An addition rate of 6% alkali-free accelerator by mass of cement was selected and used. Shotcrete nozzlemen were trained with a specially designed shotcrete training program. All shotcrete nozzlemen were qualified to shoot a basic Level I, and a more challenging Level II, for shotcrete with reinforcing steel or lattice girders. The construction quality control tests results for the project from August 2013 to December 2016 demonstrated that the shotcrete quality consistently met the project specification requirements. The projects were completed ahead of schedule because of productivity gains achieved from using wet-mix macrosynthetic fiber reinforced shotcrete. The contractors developed proper skills and techniques for application of wet-mix macrosynthetic fiber reinforced shotcrete applied by robotic sprayers with zero safety incidents or accident

Valutazione ecografica degli indici di resistività (RI) e di pulsatilità (PI) delle arterie oculari e della biometria oculare nei cani affetti da Leishmaniosi

Canine leishmaniosis is a protozoan disease endemic in the Mediterranean area, caused by Leishmania infantum. It is a chronic and severe systemic disease with various manifestation, one of these being ocular lesions. Pulsed Wave Doppler ultrasonography provides indirect information about ocular and orbital vascular flow resistance through the measurements of the Resistive (RI) e and the Pulsatility (PI) indices. The main purposes of the present study were to evaluate the ophthalmic and ciliary artery resistance and to determine the prevalence and type of ocular lesions in a population of dogs naturally infected by Leishmania infantum, before and after medical therapy. 18 dogs naturally infected by Leishmania infantum and 15 healthy dogs as a control group were included in this prospective clinical study. The results showed that ocular flow resistance was significantly higher in the sick dogs compared to the control group and that ocular and periocular tissues were affected in 83% of dogs with systemic Leishmaniasis. The ocular lesions improved or completely resolved and mean PI returned within the reference limits following the therapy, on the contrary, the mean RI remained high in dogs who have undergone therapy. Microcirculatory involvement is well recognised in canine Leishmaniasis, assessment of vascular ocular RI and PI could be a useful tool for assessing disease activity and for monitoring response to treatment

The mechanical behavior of high performance polymer fibers

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 1992.Includes bibliographical references (leaves 140-142).by John Edward Moalli.Sc.D

The cell biology of the Trichosporon-Host interaction

Fungi of the genus Trichosporon are increasingly recognized as causative agents of superficial and invasive fungal disease in humans. Although most species are considered commensals of the human skin and gastrointestinal tract, these basidiomycetes are an increasing cause of fungal disease among immunocompromised hosts, such as hematological patients and solid organ transplant recipients. The initiation of commensal or pathogenic programs by Trichosporon spp. involves the adaptation to the host microenvironment and its immune system. However, the exact virulence factors activated upon the transition to a pathogenic lifestyle, including the intricate biology of the cell wall, and how these interact with and subvert the host immune responses remain largely unknown. Here, we revisit our current understanding of the virulence attributes of Trichosporon spp., particularly T. asahii, and their interaction with the host immune system, and accommodate this knowledge within novel perspectives on fungal diagnostics and therapeutics.This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER000013), and by Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to AC, and SFRH/BPD/96176/2013 to CC).info:eu-repo/semantics/publishedVersio

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions

Background: Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). Methods: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. Results: PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73–0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). Conclusion: PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. Trial registration: NCT01535534. Registered 14.02.201

Mapping for Crisis Management DG ECHO Daily Maps and Situation Maps January – June 2024

The European Crisis Management Laboratory (ECML) Mapping Team at the Joint Research Centre (JRC), plays a crucial role in supporting the Emergency Response Coordination Centre (ERCC) with critical information. The team produces daily situational awareness reports (ECHO Daily Flash and ECHO Daily Maps) and on-demand products (ECHO Situation Maps/Infographics), such as maps and infographics, to help the ERCC understand and respond to natural disasters and crises. This document is a bi-annual report, covering the period January to June 2024, which aims to provide insights into the frequency and impact of natural disasters and crises worldwide. The analysis shows that meteorological-related events, including floods, severe weather, and landslides, are the most common type of disaster, accounting for 63.3% of all recorded events. Floods are the most common type, accounting for 36.4% of reported events, followed by landslides (20.4%), severe weather (21.3%) and tropical cyclones (5.6%). Wildfires, earthquakes, and volcanic eruptions are less frequent (3-5%), while complex emergencies and conflicts are also represented although a dedicated mapping service is provided to the European Commission on these topics. The report also examines the distribution of event types on situation maps, which summarizes the overall situation in countries, regions, or continents over extended periods. These maps help to identify complex interactions between different events. Complex Emergency is the most common event type on these maps, accounting for 36.2% of all reported events, followed by Resources (31%), which includes ECHO Partners' funding allocations. Other event types, such as wildfires, droughts, and conflicts, are also represented. The spatial distribution of event types on these maps shows that Complex Emergencies are the predominant type across Africa, particularly in the Great Horn of Africa, Sahel, and Lake Chad regions, as well as Sudan. These maps often refer to events like population displacement, food insecurity, and conflict. The ongoing conflict in Ukraine and the resulting humanitarian crisis have also led to the presence of Complex Emergency in this country.JRC.E.1 - Disaster Risk Managemen

Pathogen Recognition by the Long Pentraxin PTX3

Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogen-associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a nonredundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the cross-road between innate immunity, inflammation, and female fertility. Here, we review the studies on PTX3, with emphasis on pathogen recognition and cross-talk with other components of the innate immune system