Dating The Earliest Coins Of Athens, Corinth And Aegina

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Therapeutic depletion of natural killer cells controls persistent infection

Persistent viral infections are associated with host and viral factors that impair effective antiviral immunity. Natural killer (NK) cells contribute to establishment of persistent lymphocytic choriomeningitis virus (LCMV) infection in mice through suppression of virus-specific T cell responses during the first few days of infection, but NK cell depletion during those early time points can enable severe T cell-mediated immune pathology and death of the host. Here we show that long after their peak in cytolytic activation, NK cells continue to support viral persistence at later times of infection. Delayed depletion of NK cells, 2 to 3 weeks after infection, enhanced virus-specific T cell responses and viral control. This enhancing effect of delayed NK cell depletion on antiviral immunity, in contrast to early NK cell depletion, was not associated with increased morbidity and mortality, and mice quickly regained weight after treatment. The efficacy of the depletion depended in part upon the size of the original virus inoculum, the viral load at the time of depletion, and the presence of CD4 T cells. Each of these factors is an important contributor to the degree of CD8 T cell dysfunction during viral persistence. Thus, NK cells may continuously contribute to exhaustion of virus-specific T cells during chronic infection, possibly by depleting CD4 T cells. Targeting of NK cells could thus be considered in combination with blockade of other immunosuppressive pathways, such as the interleukin-10 (IL-10) and programmed death 1 (PD-1) pathways, as a therapy to cure chronic human infections, including those with HIV or hepatitis C virus. IMPORTANCE: Persistent virus infections are a major threat to global human health. The capacity of viruses, including HIV and hepatitis C virus, to overwhelm or subvert host immune responses contributes to a prolonged state of dampened antiviral immune functionality, which in turn facilitates viral persistence. Recent efforts have focused on therapeutics that can restore the effector functions of these functionally exhausted virus-specific T cells in order to expedite viral clearance. Here we establish that natural killer (NK) cells actively contribute to immune dysfunction and viral persistence at later stages of infection. This previously undescribed mechanism of immune suppression during chronic infection provides a vital clue for the design of novel therapeutic strategies targeting NK cell immunosuppressive activity in order to restore immune function and enhance viral control in chronically infected individuals

The value and challenges of collegiality in practice

The ability to work optimally with colleagues is considered to be a valuable determinant of success, but collegiality is a challenge to assess. Could you be more collegial, and what might be the benefits and drawbacks for clinical practice? How could you be more collegial and foster more collegiality amongst those you work with? What is collegiality and what does it mean to be collegial? Collegiality can be defined as the relationship between individuals working towards a common purpose within an organisation. The concept has its origins in the roman practice of sharing responsibility equally between government officials of the same rank in order to prevent a single individual from gaining too much power. In contrast, managerialism does not provide opportunities for exploring democratic consensus because it promotes being responsive and obedient to implementing the wishes of authority (Dearlove, 1997, King, 2004). Collegiality emphasises trust, independent thinking and sharing between co-workers. This encourages both autonomy and mutual respect and can impact on organisational efficacy (Donohoo, 2017). In modern day practice, the focus is less on sharing responsibility between officials of the same rank and more on ensuring that all employees within an organisation are treated with equal respect as individual people (Lorenzen, 2006)

Spectroscopic results from the Life in the Atacama (LITA) project 2004 field season

Analysis of spectroscopy datasets from rover field tests in the Atacama Desert (Chile), focusing on the composition of the surface and identification of potential habitats for life

Searching for life with rovers: exploration methods and science results from the 2004 field campaign of the “Life in the Atacama” project and applications to future Mars Missions

LITA develops and field tests a long-range automated rover and a science payload to search for microbial life in the Atacama. The Atacama's evolution provides a unique training ground for designing and testing exploration strategies and life detection methods for the search for life on Mars

Clonal exhaustion as a mechanism to protect against severe immunopathology and death from an overwhelming CD8 T cell response

The balance between protective immunity and immunopathology often determines the fate of the virus-infected host. How rapidly virus is cleared is a function of initial viral load, viral replication rate, and efficiency of the immune response. Here, we demonstrate, with three different inocula of lymphocytic choriomeningitis virus (LCMV), how the race between virus replication and T cell responses can result in different disease outcomes. A low dose of LCMV generated efficient CD8 T effector cells, which cleared the virus with minimal lung and liver pathology. A high dose of LCMV resulted in clonal exhaustion of T cell responses, viral persistence, and little immunopathology. An intermediate dose only partially exhausted the T cell responses and resulted in significant mortality, and the surviving mice developed viral persistence and massive immunopathology, including necrosis of the lungs and liver. This suggests that for non-cytopathic viruses like LCMV, hepatitis C virus, and hepatitis B virus, clonal exhaustion may be a protective mechanism preventing severe immunopathology and death

Use of a novel rover-mounted fluorescence imager and fluorescent probes to detect biological material in the Atacama Desert in daylight

We deployed our fluorescence imaging system which detects fluorescence signals from sparse microorganisms and biofilms on Carnegie Mellon University’s autonomous rover Zoë. The results of the 2004 Atacama Desert field season, in Chile, are discussed

Implementation of a daylight fluorescence imaging system to autonomously detect biomarkers of extant life in the Atacama Desert

We have integrated a biomarker detection system with a rover for the search for sparse life in extreme environments. The system incorporated a pulsed fluorescence imager, a reagent sprayer, and a surface scraping device for remote detection of fluorescence signals

Learning at the Interstices; Locating Practical Philosophies for Understanding Physical/virtual Inter-spaces

Virtual worlds are relatively recent developments, and so it is tempting to believe that they need to be understood through newly developed theories and philosophies. However, humans have long thought about the nature of reality and what it means to be “real.” This paper examines the three persistent philosophical concepts of Metaxis, Liminality and Space that have evolved across more than 2000 years of meditation, contemplation and reflection. Our particular focus here is on the nature of the interface between the virtual and the physical: at the interstices, and how the nature of transactions and transitions across those interfaces may impact upon learning. This may, at first, appear to be an esoteric pursuit, but we ground our arguments in primary and secondary data from research studies in higher education