The Program for climate Model diagnosis and Intercomparison: 20-th anniversary Symposium

Twenty years ago, W. Lawrence (Larry) Gates approached the U.S. Department of Energy (DOE) Office of Energy Research (now the Office of Science) with a plan to coordinate the comparison and documentation of climate model differences. This effort would help improve our understanding of climate change through a systematic approach to model intercomparison. Early attempts at comparing results showed a surprisingly large range in control climate from such parameters as cloud cover, precipitation, and even atmospheric temperature. The DOE agreed to fund the effort at the Lawrence Livermore National Laboratory (LLNL), in part because of the existing computing environment and because of a preexisting atmospheric science group that contained a wide variety of expertise. The project was named the Program for Climate Model Diagnosis and Intercomparison (PCMDI), and it has changed the international landscape of climate modeling over the past 20 years. In spring 2009 the DOE hosted a 1-day symposium to celebrate the twentieth anniversary of PCMDI and to honor its founder, Larry Gates. Through their personal experiences, the morning presenters painted an image of climate science in the 1970s and 1980s, that generated early support from the international community for model intercomparison, thereby bringing PCMDI into existence. Four talks covered GatesÃÂâÃÂÃÂÃÂÃÂs early contributions to climate research at the University of California, Los Angeles (UCLA), the RAND Corporation, and Oregon State University through the founding of PCMDI to coordinate the Atmospheric Model Intercomparison Project (AMIP). The speakers were, in order of presentation, Warren Washington [National Center for Atmospheric Research (NCAR)], Kelly Redmond (Western Regional Climate Center), George Boer (Canadian Centre for Climate Modelling and Analysis), and Lennart Bengtsson [University of Reading, former director of the European Centre for Medium-Range Weather Forecasts (ECMWF)]. The afternoon session emphasized the scientific ideas that are the basis of PCMDIÃÂâÃÂÃÂÃÂÃÂs success, summarizing their evolution and impact. Four speakers followed the various PCMDI-supported climate model intercomparison projects, beginning with early work on cloud representations in models, presented by Robert D. Cess (Distinguished Professor Emeritus, Stony Brook University), and then the latest Cloud Feedback Model Intercomparison Projects (CFMIPs) led by Sandrine Bony (Laboratoire de MÃÂÃÂÃÂétÃÂÃÂÃÂéorologie Dynamique). Benjamin Santer (LLNL) presented a review of the climate change detection and attribution (D & A) work pioneered at PCMDI, and Gerald A. Meehl (NCAR) ended the day with a look toward the future of climate change research

Streptococcus pneumoniae NanC. Structural insights into the specificity and mechanism of a sialidase that produces a sialidase inhibitor

This work was supported by the Biotechnology and Biological Sciences Research Council (UK) and the Medical Research Council (UK).Streptococcus pneumoniae is an important human pathogen that causes a range of disease states. Sialidases are important bacterial virulence factors. There are three pneumococcal sialidases: NanA, NanB, and NanC. NanC is an unusual sialidase in that its primary reaction product is 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, also known as DANA), a nonspecific hydrolytic sialidase inhibitor. The production of Neu5Ac2en from α2-3-linked sialosides by the catalytic domain is confirmed within a crystal structure. A covalent complex with 3-fluoro-β-N-acetylneuraminic acid is also presented, suggesting a common mechanism with other sialidases up to the final step of product formation. A conformation change in an active site hydrophobic loop on ligand binding constricts the entrance to the active site. In addition, the distance between the catalytic acid/base (Asp-315) and the ligand anomeric carbon is unusually short. These features facilitate a novel sialidase reaction in which the final step of product formation is direct abstraction of the C3 proton by the active site aspartic acid, forming Neu5Ac2en. NanC also possesses a carbohydrate-binding module, which is shown to bind α2-3- and α2-6-linked sialosides, as well as N-acetylneuraminic acid, which is captured in the crystal structure following hydration of Neu5Ac2en by NanC. Overall, the pneumococcal sialidases show remarkable mechanistic diversity while maintaining a common structural scaffold.Publisher PDFPeer reviewe

Hybrid Representation Learning for Cognitive Diagnosis in Late-Life Depression Over 5 Years with Structural MRI

Late-life depression (LLD) is a highly prevalent mood disorder occurring in older adults and is frequently accompanied by cognitive impairment (CI). Studies have shown that LLD may increase the risk of Alzheimer's disease (AD). However, the heterogeneity of presentation of geriatric depression suggests that multiple biological mechanisms may underlie it. Current biological research on LLD progression incorporates machine learning that combines neuroimaging data with clinical observations. There are few studies on incident cognitive diagnostic outcomes in LLD based on structural MRI (sMRI). In this paper, we describe the development of a hybrid representation learning (HRL) framework for predicting cognitive diagnosis over 5 years based on T1-weighted sMRI data. Specifically, we first extract prediction-oriented MRI features via a deep neural network, and then integrate them with handcrafted MRI features via a Transformer encoder for cognitive diagnosis prediction. Two tasks are investigated in this work, including (1) identifying cognitively normal subjects with LLD and never-depressed older healthy subjects, and (2) identifying LLD subjects who developed CI (or even AD) and those who stayed cognitively normal over five years. To the best of our knowledge, this is among the first attempts to study the complex heterogeneous progression of LLD based on task-oriented and handcrafted MRI features. We validate the proposed HRL on 294 subjects with T1-weighted MRIs from two clinically harmonized studies. Experimental results suggest that the HRL outperforms several classical machine learning and state-of-the-art deep learning methods in LLD identification and prediction tasks

Sustained pain-related depression of behavior: effects of intraplantar formalin and complete freund’s adjuvant on intracranial self-stimulation (ICSS) and endogenous kappa opioid biomarkers in rats

Background: Intraplantar administration of complete Freund's adjuvant (CFA) and formalin are two noxious stimuli commonly used to produce sustained pain-related behaviors in rodents for research on neurobiology and treatment of pain. One clinically relevant manifestation of pain is depression of behavior and mood. This study compared effects of intraplantar CFA and formalin on depression of positively reinforced operant behavior in an assay of intracranial self-stimulation (ICSS) in rats. Effects of CFA and formalin on other physiological and behavioral measures, and opioid effects on formalin-induced depression of ICSS, were also examined. Results: There were four main findings. First, consistent with previous studies, both CFA and formalin produced similar paw swelling and mechanical hypersensitivity. Second, CFA produced weak and transient depression of ICSS, whereas formalin produced a more robust and sustained depression of ICSS that lasted at least 14 days. Third, formalin-induced depression of ICSS was reversed by morphine doses that did not significantly alter ICSS in saline-treated rats, suggesting that formalin effects on ICSS can be interpreted as an example of pain-related and analgesic-reversible depression of behavior. Finally, formalin-induced depression of ICSS was not associated with changes in central biomarkers for activation of endogenous kappa opioid systems, which have been implicated in depressive-like states in rodents, nor was it blocked by the kappa antagonist norbinaltorphimine. Conclusions: These results suggest differential efficacy of sustained pain stimuli to depress brain reward function in rats as assessed with ICSS. Formalin-induced depression of ICSS does not appear to engage brain kappa opioid systems. Electronic supplementary material The online version of this article (doi:10.1186/1744-8069-10-62) contains supplementary material, which is available to authorized users

Collaboration in the Semantic Grid: a Basis for e-Learning

The CoAKTinG project aims to advance the state of the art in collaborative mediated spaces for the Semantic Grid. This paper presents an overview of the hypertext and knowledge based tools which have been deployed to augment existing collaborative environments, and the ontology which is used to exchange structure, promote enhanced process tracking, and aid navigation of resources before, after, and while a collaboration occurs. While the primary focus of the project has been supporting e-Science, this paper also explores the similarities and application of CoAKTinG technologies as part of a human-centred design approach to e-Learning

Aquatic biosurvey of the Lovell River on UNH land

We assessed the physical, chemical and biological conditions at two sites along the Lovell River on University of New Hampshire (UNH) -owned conservation land. The discharge was 4.4 m3 s-1 at Site 1 and 5.7 m3 s -1 downstream at Site 2. Canopy coverage ranged from 8-25%. Canopy was dominated by Eastern Hemlock (79-84%). Much of the stream was strewn with large boulders and the substrate consisted of rocks of highly variable sizes ( 3-549 cm dia.). Specific conductivity (22.1-23.3 µS), pH (6.4) and temperature (7.9-8.3 °C) varied little between sites. Macro-invertebrate bio-indices indicated either excellent water quality with no apparent organic pollution (3.0/10) or good water quality with possible slight organic pollution (4.4/10)

The Mississippian Section at Paddys Bluff, Crittenden County, Kentucky

Paddys Bluff (Figs. 1-3) is located on the south side of the Illinois Basin on the Cumberland River, 1.7 miles downstream from Dycusburg in Crittenden County, Ky., in Carter coordinate section 23-I-16 and ecoregion 71f of the Western Highland Rim of Kentucky (Woods and others, 2002). This bluff is on a right-descending bend 18 liver miles above its junction with the Ohio River at Smithland, Livingston County. The bluff (Figs. 4A, B) is locally famous as the location for a scene from the classic 1962 film, How the West Was Won,\u27 a winner of three Academy Awards, starling James Stewart, John Wayne, and others. We observed Paddys Bluff from the starboard Texas deck of the steamboat Della Queen one rainy morning in October 2005; the thick, persistent white bed midway in the bluff especially attracted our attention (Fig. 4). Paddys Bluff is the best natural exposure of Mississippian limestone between Barkley Dam and the Ohio River, a distance of 31 river miles. The bluff, some 1,700 feet long (Fig. 4), rises 160 feet above the Cumberland River and deflects it about 16° into a long westward reach, the river removing all talus at the base of the bluff. The bluff lies in a graben between two inferred faults st liking N40 to 45°E (Amos and Hayes, 1974). Readily seen in the limestones along the river at the base of the bluff is a prominent joint set parallel to these faults. This bluff is mapped on the Dycusburg geologic quadrangle map (Table 1) as the combined Salem and St. Louis Limestones (Amos and Hayes, 1974) and is capped by at least 15 feet of poorly exposed gravel of the Cretaceous Tuscaloosa Formation (Olive, 1980). Across the river less than 2 miles distant are scattered continental deposits of reddish brown Lafayette-type, sandy cobble-gravel (Olive, 1980), below which are outliers of the Cretaceous Tuscaloosa Formation; both cap hilltops of the same underlying Mississippian limestones. Why is Paddys Bluff of interest? There are at least six reasons to study it. First, can the Salem and St. Louis Limestones be individually identified at the bluff? If, in fact, they can be separated, the upper boundary of sequence S4 recognized in the Lake Cumberland area of south-central Kentucky by Khetani and Read (2002, Fig. 12) extends much farther west. Still another challenge is the enigmatic, massive, fine-grained, whitish-weathering carbonate mudstone bed, unit C of our section, high in the bluff. What does it represent? How widespread is it? Why do beds below rt have a strong petroliferous odor and not those above it? Why are some of the coral heads (Fig. 5) at Paddys Bluff overturned and others not? The last challenge is the bluff itself: Why is it there and how long has it been there

Whole home exercise intervention for depression in older care home residents (the OPERA study) : a process evaluation

Background: The ‘Older People’s Exercise intervention in Residential and nursing Accommodation’ (OPERA) cluster randomised trial evaluated the impact of training for care home staff together with twice-weekly, physiotherapist-led exercise classes on depressive symptoms in care home residents, but found no effect. We report a process evaluation exploring potential explanations for the lack of effect. Methods: The OPERA trial included over 1,000 residents in 78 care homes in the UK. We used a mixed methods approach including quantitative data collected from all homes. In eight case study homes, we carried out repeated periods of observation and interviews with residents, care staff and managers. At the end of the intervention, we held focus groups with OPERA research staff. We reported our first findings before the trial outcome was known. Results: Homes showed large variations in activity at baseline and throughout the trial. Overall attendance rate at the group exercise sessions was low (50%). We considered two issues that might explain the negative outcome: whether the intervention changed the culture of the homes, and whether the residents engaged with the intervention. We found low levels of staff training, few home champions for the intervention and a culture that prioritised protecting residents from harm over encouraging activity. The trial team delivered 3,191 exercise groups but only 36% of participants attended at least 1 group per week and depressed residents attended significantly fewer groups than those who were not depressed. Residents were very frail and therefore most groups only included seated exercises. Conclusions: The intervention did not change the culture of the homes and, in the case study homes, activity levels did not change outside the exercise groups. Residents did not engage in the exercise groups at a sufficient level, and this was particularly true for those with depressive symptoms at baseline. The physical and mental frailty of care home residents may make it impossible to deliver a sufficiently intense exercise intervention to impact on depressive symptoms

Sourcing illegal drugs as a hidden older user: the ideal of ‘social supply’

Aims: At a time of growing awareness regarding the non-commercial supply of illegal drugs between friends, this article explores the significance of so-called ‘social supply’ for a group of ‘hidden’ users of illegal drugs aged 40 and over. Methodology: Semi-structured interviews were conducted with 30 users of illegal drugs aged 40 and over who were not in contact with the criminal justice system or treatment agencies regarding their use. Participants were recruited using snowball sampling. Findings: Accessing drugs through the commercial market was considered as a less attractive proposition than social supply by the participants. The majority used only socially supplied drugs, with some engaging commercial dealers when socially supplied product was unavailable. A handful sourced drugs exclusively through the commercial market. Some were home growers of cannabis, and a small number had drifted into social supply themselves. Conclusions: Social supply was seen in a far more favourable light than commercial transactions by our participants, and acted as an ideal against which all other acts of sourcing were compared. Moreover, social supply was often an integral facet of the drug using experience and served to validate and enhance that experience. The relatively benign, non-predatory nature of the social supply engaged in by the participants lends support to calls for some reform of the offence of supply in UK law