Overview of NASA's Carbon Monitoring System Flux-Pilot Project

NASA's space-based observations of physical, chemical and biological parameters in the Earth System along with state-of-the-art modeling capabilities provide unique capabilities for analyses of the carbon cycle. The Carbon Monitoring System is developing an exploratory framework for detecting carbon in the environment and its changes, with a view towards contributing to national and international monitoring activities. The Flux-Pilot Project aims to provide a unified view of land-atmosphere and ocean-atmosphere carbon exchange, using observation-constrained models. Central to the project is the application of NASA's satellite observations (especially MODIS), the ACOS retrievals of the JAXA-GOSAT observations, and the "MERRA" meteorological reanalysis produced with GEOS-S. With a primary objective of estimating uncertainty in computed fluxes, two land- and two ocean-systems are run for 2009-2010 and compared with existing flux estimates. An transport model is used to evaluate simulated CO2 concentrations with in-situ and space-based observations, in order to assess the realism of the fluxes and how uncertainties in fluxes propagate into atmospheric concentrations that can be more readily evaluated. Finally, the atmospheric partial CO2 columns observed from space are inverted to give new estimates of surface fluxes, which are evaluated using the bottom-up estimates and independent datasets. The focus of this presentation will be on the science goals and current achievements of the pilot project, with emphasis on how policy-relevant questions help focus the scientific direction. Examples include the issue of what spatio-temporal resolution of fluxes can be detected from polar-orbiting satellites and whether it is possible to use space-based observations to separate contributions to atmospheric concentrations of (say) fossil-fuel and biological activit

Assimilation of SCIAMACHY Total Column CO Observations: Regional Analysis of Data Impact

Carbon monoxide (CO) total column observations from the SCanning Imaging Absorption SpectroMeter for Atmospheric CHartography (SCIAMACHY) on board ENVISAT are assimilated into the Global Modeling and Assimilation Office (GMAO) constituent assimilation system for the period July 18-October 31, 2004. This is the first assimilation of CO observations from a near infrared sounder. The impact of the assimilation on CO distribution is evaluated using independent Measurement of Ozone and Water vapor by Airbus In-service Aircraft (MOZAIC) in-situ CO profiles. Assimilation of satellite data improves agreement with MOZAIC CO globally, especially in the upper troposphere

A Src-Like Inactive Conformation in the Abl Tyrosine Kinase Domain

The improper activation of the Abl tyrosine kinase results in chronic myeloid leukemia (CML). The recognition of an inactive conformation of Abl, in which a catalytically important Asp-Phe-Gly (DFG) motif is flipped by approximately 180° with respect to the active conformation, underlies the specificity of the cancer drug imatinib, which is used to treat CML. The DFG motif is not flipped in crystal structures of inactive forms of the closely related Src kinases, and imatinib does not inhibit c-Src. We present a structure of the kinase domain of Abl, determined in complex with an ATP–peptide conjugate, in which the protein adopts an inactive conformation that resembles closely that of the Src kinases. An interesting aspect of the Src-like inactive structure, suggested by molecular dynamics simulations and additional crystal structures, is the presence of features that might facilitate the flip of the DFG motif by providing room for the phenylalanine to move and by coordinating the aspartate side chain as it leaves the active site. One class of mutations in BCR–Abl that confers resistance to imatinib appears more likely to destabilize the inactive Src-like conformation than the active or imatinib-bound conformations. Our results suggest that interconversion between distinctly different inactive conformations is a characteristic feature of the Abl kinase domain

Experimental characterization and automatic identification of stridulatory sounds inside wood

The propagation of animal vocalizations in water and in air is a well-studied phenomenon, but sound produced by bark and wood-boring insects, which feed and reproduce inside trees, is poorly understood. Often being confined to the dark and chemically saturated habitat of wood, many bark-and woodborers have developed stridulatory mechanisms to communicate acoustically. Despite their ecological and economic importance and the unusual medium used for acoustic communication, very little is known about sound production in these insects, or their acoustic interactions inside trees. Here, we use bark beetles (Scolytinae) as a model system to study the effects of wooden tissue on the propagation of insect stridulations and propose algorithms for their automatic identification. We characterize distance dependence of the spectral parameters of stridulatory sounds, propose data-based models for the power decay of the stridulations in both outer and inner bark, provide optimal spectral ranges for stridulation detectability and develop automatic methods for their detection and identification. We also discuss the acoustic discernibility of species cohabitating the same log. The species tested can be acoustically identified with 99% of accuracy at distances up to 20 cm and detected to the greatest extent in the 2-6 kHz frequency band. Phloem was a better medium for sound transmission than bark

Golden key local evaluation - Phase 5 final report

This final local evaluation report marks the culmination of an intensive eight-years following the work of Golden Key (GK) to transform services for people in Bristol with severe and multiple disadvantage. Previous phases of the local evaluation have explored systems change (phases 3 and 4), the client experience (phase 2), and development of the partnership (phase 1). This last phase (phase 5) has focused particularly on:•Understanding the change experienced by clients through GK’s support•Capturing GK’s learning of person-centred and trauma informed client support approaches•Reviewing how the voice of lived experience has contributed to G

Aura Microwave Limb Sounder Observations of Dynamics and Transport During the Record-Breaking 2009 Arctic Stratospheric Major Warming

A major stratospheric sudden warming (SSW) in January 2009 was the strongest and most prolonged on record. Aura Microwave Limb Sounder (MLS) observations are used to provide an overview of dynamics and transport during the 2009 SSW, and to compare with the intense, long-lasting SSW in January 2006. The Arctic polar vortex split during the 2009 SSW, whereas the 2006 SSW was a vortex displacement event. Winds reversed to easterly more rapidly and reverted to westerly more slowly in 2009 than in 2006. More mixing of trace gases out of the vortex during the decay of the vortex fragments, and less before the fulfillment of major SSW criteria, was seen in 2009 than in 2006; persistent well-defined fragments of vortex and anticyclone air were more prevalent in 2009. The 2009 SSW had a more profound impact on the lower stratosphere than any previously observed SSW, with no significant recovery of the vortex in that region. The stratopause breakdown and subsequent reformation at very high altitude, accompanied by enhanced descent into a rapidly strengthening upper stratospheric vortex, were similar in 2009 and 2006. Many differences between 2006 and 2009 appear to be related to the different character of the SSWs in the two years

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7. Furthermore, PSC activation occurs very early during PDAC tumorigenesis8-10, and activated PSCs comprise a substantial fraction of the tumour mass, providing a rich source of readily detectable factors. Therefore, we hypothesized that the communication between PSCs and PCCs could be an exploitable target to develop effective strategies for PDAC therapy and diagnosis. Here, starting with a systematic proteomic investigation of secreted disease mediators and underlying molecular mechanisms, we reveal that leukaemia inhibitory factor (LIF) is a key paracrine factor from activated PSCs acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slow tumour progression and augment the efficacy of chemotherapy to prolong survival of PDAC mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human PDAC, aberrant production of LIF in the pancreas is restricted to pathological conditions and correlates with PDAC pathogenesis, and changes in the levels of circulating LIF correlate well with tumour response to therapy. Collectively, these findings reveal a function of LIF in PDAC tumorigenesis, and suggest its translational potential as an attractive therapeutic target and circulating marker. Our studies underscore how a better understanding of cell-cell communication within the tumour microenvironment can suggest novel strategies for cancer therapy

A rational roadmap for SARS-CoV-2/COVID-19 pharmacotherapeutic research and development: IUPHAR Review 29.

In this review, we identify opportunities for drug discovery in the treatment of COVID-19 and, in so doing, provide a rational roadmap whereby pharmacology and pharmacologists can mitigate against the global pandemic. We assess the scope for targeting key host and viral targets in the mid-term, by first screening these targets against drugs already licensed, an agenda for drug repurposing, which should allow rapid translation to clinical trials. A simultaneous, multi-pronged approach using conventional drug discovery methods aimed at discovering novel chemical and biological means of targeting a short list of host and viral entities which should extend the arsenal of anti-SARS-CoV-2 agents. This longer term strategy would provide a deeper pool of drug choices for future-proofing against acquired drug resistance. Second, there will be further viral threats, which will inevitably evade existing vaccines. This will require a coherent therapeutic strategy which pharmacology and pharmacologists are best placed to provide. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.Welcome Trust 107715/Z/15/

What are the barriers to care integration for those at the advanced stages of dementia living in care homes in the UK? Health care professional perspective

yesPeople with advanced dementia are frequently bed-bound, doubly incontinent and able to speak only a few words. Many reside in care homes and may often have complex needs requiring efficient and timely response by knowledgeable and compassionate staff. The aim of this study is to improve our understanding of health care professionals’ attitudes and knowledge of the barriers to integrated care for people with advanced dementia. In-depth, interactive interviews conducted with 14 health care professionals including commissioners, care home managers, nurses and health care assistants in the UK. Barriers to care for people with advanced dementia are influenced by governmental and societal factors which contribute to challenging environments in care homes, poor morale amongst care staff and a fragmentation of health and social care at the end of life. Quality of care for people with dementia as they approach death may be improved by developing collaborative networks to foster improved relationships between health and social care services

Quantifying the Observability of CO2 Flux Uncertainty in Atmospheric CO2 Records Using Products from Nasa's Carbon Monitoring Flux Pilot Project

NASAs Carbon Monitoring System (CMS) Flux Pilot Project (FPP) was designed to better understand contemporary carbon fluxes by bringing together state-of-the art models with remote sensing datasets. Here we report on simulations using NASAs Goddard Earth Observing System Model, version 5 (GEOS-5) which was used to evaluate the consistency of two different sets of observationally constrained land and ocean fluxes with atmospheric CO2 records. Despite the strong data constraint, the average difference in annual terrestrial biosphere flux between the two land (NASA Ames CASA and CASA-GFED) models is 1.7 Pg C for 2009-2010. Ocean models (NOBM and ECCO2-Darwin) differ by 35 in their global estimates of carbon flux with particularly strong disagreement in high latitudes. Based upon combinations of terrestrial and ocean fluxes, GEOS-5 reasonably simulated the seasonal cycle observed at northern hemisphere surface sites and by the Greenhouse gases Observing SATellite (GOSAT) while the model struggled to simulate the seasonal cycle at southern hemisphere surface locations. Though GEOS-5 was able to reasonably reproduce the patterns of XCO2 observed by GOSAT, it struggled to reproduce these aspects of AIRS observations. Despite large differences between land and ocean flux estimates, resulting differences in atmospheric mixing ratio were small, typically less than 5 ppmv at the surface and 3 ppmv in the XCO2 column. A statistical analysis based on the variability of observations shows that flux differences of these magnitudes are difficult to distinguish from natural variability, regardless of measurement platform