Morphology of the archaellar motor and associated cytoplasmic cone in Thermococcus kodakaraensis

Archaeal swimming motility is driven by archaella: rotary motors attached to long extracellular filaments. The structure of these motors, and particularly how they are anchored in the absence of a peptidoglycan cell wall, is unknown. Here, we use electron cryotomography to visualize the archaellar basal body in vivo in Thermococcus kodakaraensis KOD1. Compared to the homologous bacterial type IV pilus (T4P), we observe structural similarities as well as several unique features. While the position of the cytoplasmic ATPase appears conserved, it is not braced by linkages that extend upward through the cell envelope as in the T4P, but rather by cytoplasmic components that attach it to a large conical frustum up to 500 nm in diameter at its base. In addition to anchoring the lophotrichous bundle of archaella, the conical frustum associates with chemosensory arrays and ribosome‐excluding material and may function as a polar organizing center for the coccoid cells

Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors:a feasibility study

INTRODUCTION: Glycolytic activity and hypoxia are associated with poor prognosis and radiation resistance. Including both the tumor uptake of 2-deoxy-2-[(18) F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer copper(II)diacetyl-bis(N(4))-methylsemithio-carbazone (Cu-ATSM) in targeted therapy planning may therefore lead to improved tumor control. In this study we analyzed the overlap between sub-volumes of FDG and hypoxia assessed by the uptake of (64)Cu-ATSM in canine solid tumors, and evaluated the possibilities for dose redistribution within the gross tumor volume (GTV). MATERIALS AND METHODS: Positron emission tomography/computed tomography (PET/CT) scans of five spontaneous canine solid tumors were included. FDG-PET/CT was obtained at day 1, (64)Cu-ATSM at day 2 and 3 (3 and 24 h pi.). GTV was delineated and CT images were co-registered. Sub-volumes for 3 h and 24 h (64)Cu-ATSM (Cu3 and Cu24) were defined by a threshold based method. FDG sub-volumes were delineated at 40% (FDG40) and 50% (FDG50) of SUV(max). The size of sub-volumes, intersection and biological target volume (BTV) were measured in a treatment planning software. By varying the average dose prescription to the tumor from 66 to 85 Gy, the possible dose boost (D( B )) was calculated for the three scenarios that the optimal target for the boost was one, the union or the intersection of the FDG and (64)Cu-ATSM sub-volumes. RESULTS: The potential boost volumes represented a fairly large fraction of the total GTV: Cu3 49.8% (26.8-72.5%), Cu24 28.1% (2.4-54.3%), FDG40 45.2% (10.1-75.2%), and FDG50 32.5% (2.6-68.1%). A BTV including the union (∪) of Cu3 and FDG would involve boosting to a larger fraction of the GTV, in the case of Cu3∪FDG40 63.5% (51.8-83.8) and Cu3∪FDG50 48.1% (43.7-80.8). The union allowed only a very limited D( B ) whereas the intersection allowed a substantial dose escalation. CONCLUSIONS: FDG and (64)Cu-ATSM sub-volumes were only partly overlapping, suggesting that the tracers offer complementing information on tumor physiology. Targeting the combined PET positive volume (BTV) for dose escalation within the GTV results in a limited D( B ). This suggests a more refined dose redistribution based on a weighted combination of the PET tracers in order to obtain an improved tumor control

The Ross Sea Dipole-temperature, snow accumulation and sea ice variability in the Ross Sea region, Antarctica, over the past 2700 years

High-resolution, well-dated climate archives provide an opportunity to investigate the dynamic interactions of climate patterns relevant for future projections. Here, we present data from a new, annually dated ice core record from the eastern Ross Sea, named the Roosevelt Island Climate Evolution (RICE) ice core. Comparison of this record with climate reanalysis data for the 1979-2012 interval shows that RICE reliably captures temperature and snow precipitation variability in the region. Trends over the past 2700 years in RICE are shown to be distinct from those in West Antarctica and the western Ross Sea captured by other ice cores. For most of this interval, the eastern Ross Sea was warming (or showing isotopic enrichment for other reasons), with increased snow accumulation and perhaps decreased sea ice concentration. However, West Antarctica cooled and the western Ross Sea showed no significant isotope temperature trend. This pattern here is referred to as the Ross Sea Dipole. Notably, during the Little Ice Age, West Antarctica and the western Ross Sea experienced colder than average temperatures, while the eastern Ross Sea underwent a period of warming or increased isotopic enrichment. From the 17th century onwards, this dipole relationship changed. All three regions show current warming, with snow accumulation declining in West Antarctica and the eastern Ross Sea but increasing in the western Ross Sea. We interpret this pattern as reflecting an increase in sea ice in the eastern Ross Sea with perhaps the establishment of a modern Roosevelt Island polynya as a local moisture source for RICE

Criteria for priority setting of HIV/AIDS interventions in Thailand: a discrete choice experiment

Contains fulltext : 87849.pdf (publisher's version ) (Open Access)BACKGROUND: Although a sizeable budget is available for HIV/AIDS control in Thailand, there will never be enough resources to implement every programme for all target groups at full scale. As such, there is a need to prioritize HIV/AIDS programmes. However, as of yet, there is no evidence on the criteria that should guide the priority setting of HIV/AIDS programmes in Thailand, including their relative importance. Also, it is not clear whether different stakeholders share similar preferences. METHODS: Criteria for priority setting of HIV/AIDS interventions in Thailand were identified in group discussions with policy makers, people living with HIV/AIDS (PLWHA), and community members (i.e. village health volunteers (VHVs)). On the basis of these, discrete choice experiments were designed and administered among 28 policy makers, 74 PLWHA, and 50 VHVs. RESULTS: In order of importance, policy makers expressed a preference for interventions that are highly effective, that are preventive of nature (as compared to care and treatment), that are based on strong scientific evidence, that target high risk groups (as compared to teenagers, adults, or children), and that target both genders (rather than only men or women). PLWHA and VHVs had similar preferences but the former group expressed a strong preference for care and treatment for AIDS patients. CONCLUSIONS: The study has identified criteria for priority setting of HIV/AIDS interventions in Thailand, and revealed that different stakeholders have different preferences vis-a-vis these criteria. This could be used for a broad ranking of interventions, and as such as a basis for more detailed priority setting, taking into account also qualitative criteria