Approach

We describe the design and initial implementation of a system for constructing a haptic model of a mathematical function for exploration using a PHANToM. The model is that of a block of balsa wood with the trace of the function carved into its surface. Problem Statement It is difficult to teach some kinds of mathematics without using graphical representations of functions. In this paper we describe the design of a proposed haptic application and the implementation of a prototype using a PHANToM which will allow a blind student to feel the shape of a function being studied. Related Work Some of our previous work has been in constructing PHANToM-based haptic maps for mobility training. [1] Other VE Lab members are constructing haptic models of atoms. [2

Unique archaeal assemblages in the Arctic Ocean unveiled by massively parallel tag sequencing

10 páginas, 4 figuras, 1 tabla.The Arctic Ocean plays a critical role in controlling nutrient budgets between the Pacific and Atlantic Ocean. Archaea are key players in the nitrogen cycle and in cycling nutrients, but their community composition has been little studied in the Arctic Ocean. Here, we characterize archaeal assemblages from surface and deep Arctic water masses using massively parallel tag sequencing of the V6 region of the 16S rRNA gene. This approach gave a very high coverage of the natural communities, allowing a precise description of archaeal assemblages. This first taxonomic description of archaeal communities by tag sequencing reported so far shows that it is possible to assign an identity below phylum level to most (95%) of the archaeal V6 tags, and shows that tag sequencing is a powerful tool for resolving the diversity and distribution of specific microbes in the environment. Marine group I Crenarchaeota was overall the most abundant group in the Arctic Ocean and comprised between 27% and 63% of all tags. Group III Euryarchaeota were more abundant in deep-water masses and represented the largest archaeal group in the deep Atlantic layer of the central Arctic Ocean. Coastal surface waters, in turn, harbored more group II Euryarchaeota. Moreover, group II sequences that dominated surface waters were different from the group II sequences detected in deep waters, suggesting functional differences in closely related groups. Our results unveiled for the first time an archaeal community dominated by group III Euryarchaeota and show biogeographical traits for marine Arctic Archaea.P E Galand is supported by a Marie Curie grant (CRENARC MEIF-CT-2007–040247). EO Casamayor was supported by a Spanish grant CGL2006–12058-BOS, and D L Kirchman by NSF OPP ARC-0632233. C Lovejoy would like to acknowledge the support of the Natural Sciences and Engineering Council, Canada (NSERC) Special Research Opportunity Fund. We thank C Pedros-Alio for support during CASES. Deep Arctic samples were collected by K Scarcella and E Didierjean, and we thank the Chief Scientist, Officers and Crew of the CCGS Louis St Laurent and support from Fisheries and Oceans Canada. Tag sequencing was supported by a Keck foundation grant to M Sogin and L Ameral Zettler. This is a contribution to the International Census of Marine Microbes (ICOMM).Peer reviewe

Toll-like receptor–induced changes in glycolytic metabolism regulate dendritic cell activation

Dendritic cells (DCs) are key regulators of innate and acquired immunity. The maturation of DCs is directed by signal transduction events downstream of toll-like receptors (TLRs) and other pattern recognition receptors. Here, we demonstrate that, in mouse DCs, TLR agonists stimulate a profound metabolic transition to aerobic glycolysis, similar to the Warburg metabolism displayed by cancer cells. This metabolic switch depends on the phosphatidyl inositol 3′-kinase/Akt pathway, is antagonized by the adenosine monophosphate (AMP)–activated protein kinase (AMPK), and is required for DC maturation. The metabolic switch induced by DC activation is antagonized by the antiinflammatory cytokine interleukin-10. Our data pinpoint TLR-mediated metabolic conversion as essential for DC maturation and function and reveal it as a potential target for intervention in the control of excessive inflammation and inappropriately regulated immune responses

A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease

OBJECTIVE: To determine if future studies of coenzyme Q10 and GPI-1485 in Parkinson disease (PD) may be warranted. METHODS: We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold. RESULTS: The primary outcome measure (change in total Unified Parkinson\u27s Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed. CONCLUSIONS: Coenzyme Q10 and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies. ©2007 AAN Enterprises, Inc

Review series on helminths, immune modulation and the hygiene hypothesis: Mechanisms underlying helminth modulation of dendritic cell function

Dendritic cells (DCs) play a central role in activating CD4 T (T helper, Th) cells. As a component of their response to pathogen-associated stimuli, DCs produce cytokines and express surface molecules that provide important cues to modulate the effector functions of responding Th cells. Much is known of how DCs respond to, and influence immune response outcome to, bacterial and viral pathogens. However, relatively little is understood about how DCs respond to helminth parasites. This is an area of considerable interest since it impacts our understanding of the initiation of Th2 responses, which are stereotypically associated with helminth infections, and the regulation of allergic and autoimmune pathologies which evidence suggests are less severe or absent in individuals infected with helminths. This review attempts to summarize our understanding of the effects of helminth products on dendritic cell biology

A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease

BACKGROUNDCreatine and minocycline were prioritized for testing in Phase II clinical trials based on a systematic evaluation of potentially disease modifying compounds for Parkinson disease (PD).OBJECTIVETo test whether creatine and minocycline alter the course of early PD relative to a predetermined futility threshold for progression of PD in a randomized, double-blind, Phase II futility clinical trial. Agents that do not perform better than the futility threshold are rejected as futile and are not considered for further study.METHODSParticipants had a diagnosis of PD within 5 years, but did not require medications for the management of symptoms. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to either the time when there was sufficient disability to warrant symptomatic therapy for PD or 12 months, whichever came first. Subjects were randomized 1:1:1 to receive creatine 10 g/day, minocycline 200 mg/day, or matching placebo. The futility threshold was set as a 30% reduction in UPDRS progression based on the placebo/tocopherol arm of the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) trial. p values < or = 0.1 indicate futility.RESULTSTwo hundred subjects were randomized to the three groups. Neither creatine (p = 0.96) nor minocycline (p = 0.66) could be rejected as futile based on the DATATOP futility threshold. The rate of progression for the calibration placebo group fell outside the 95% CI for the DATATOP historical control. In a sensitivity analysis, based on the threshold derived from the calibration placebo group, again neither drug could be rejected as futile. Tolerability was 91% in the creatine group and 77% in the minocycline group. Common adverse events included upper respiratory symptoms (26%), joint pain (19%), and nausea (17%).CONCLUSIONSBoth creatine and minocycline should be considered for definitive Phase III trials to determine if they alter the long term progression of Parkinson disease (PD). Additional factors must be weighed before selecting agents for Phase III trials, including safety, tolerability, activity, cost, and availability of these two agents in comparison with other agents currently in development for PD

A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease

OBJECTIVETo determine if future studies of coenzyme Q(10) and GPI-1485 in Parkinson disease (PD) may be warranted.METHODSWe conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold.RESULTSThe primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed.CONCLUSIONSCoenzyme Q(10) and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies