Pharmacological activation of the nuclear receptor REV-ERB reverses cognitive deficits and reduces amyloid-β burden in a mouse model of Alzheimer’s disease

Alzheimer’s disease currently lacks treatment options that effectively reverse the biological/anatomical pathology and cognitive deficits associated with the disease. Loss of function of the nuclear receptor REV-ERB is associated with reduced cognitive function in mouse models. The effect of enhanced REV-ERB activity on cognitive function has not been examined. In this study, we tested the hypothesis that enhanced REV-ERB function may enhance cognitive function in a model of Alzheimer’s disease. We utilized the REV-ERB agonist SR9009 to pharmacologically activate the activity of REV-ERB in the SAMP8 mouse model of Alzheimer’s disease. SR9009 reversed cognitive dysfunction of an aged SAMP8 mouse in several behavioral assays including novel object recognition, T-maze foot shock avoidance, and lever press operant conditioning task assessments. SR9009 treatment reduced amyloid-β 1–40 and 1–42 levels in the cortex, which is consistent with improved cognitive function. Furthermore, SR9009 treatment led to increased hippocampal PSD-95, cortical synaptophysin expression and the number of synapses suggesting improvement in synaptic function. We conclude that REV-ERB is a potential target for treatment of Alzheimer’s disease.</div

Unexpected Features of Supersymmetry with Central Charges

It is shown that N=2 supersymmetric theories with central charges present some hidden quartic symmetry. This enables us to construct representations of the quartic structure induced by superalgebra representations.Comment: 14 pages, more details have been given, to appear in J. Phys.

Ternary algebras and groups

We construct explicitly groups associated to specific ternary algebras which extend the Lie (super)algebras (called Lie algebras of order three). It turns out that the natural variables which appear in this construction are variables which generate the three-exterior algebra. An explicit matrix representation of a group associated to a peculiar Lie algebra of order three is constructed considering matrices with entry which belong to the three exterior algebra.Comment: 11 pages contribution to the 5th International Symposium on Quantum Theory and Symmetries (QTS5

Design of the Spitzer Space Telescope Heritage Archive

It is predicted that Spitzer Space Telescope’s cryogen will run out in April 2009, and the final reprocessing for the cryogenic mission is scheduled to end in April 2011, at which time the Spitzer archive will be transferred to the NASA/IPAC Infrared Science Archive (IRSA) for long-term curation. The Spitzer Science Center (SSC) and IRSA are collaborating to design and deploy the Spitzer Heritage Archive (SHA), which will supersede the current Spitzer archive. It will initially contain the raw and final reprocessed cryogenic science products, and will eventually incorporate the final products from the Warm mission. The SHA will be accompanied by tools deemed necessary to extract the full science content of the archive and by comprehensive documentation

REDUCED KINETIC MECHANISM FOR REACTIVE FLOW SIMULATION OF SYNGAS/METHANE COMBUSTION AT GAS TURBINE CONDITIONS

ABSTRACT The reduced kinetic mechanism for syngas/methane developed in the present work consists of a global reaction step for fuel decomposition in which the fuel molecule breaks down into CH 2 O and H 2 . A detailed CH 2 O/H 2 /O 2 elementary reaction sub-set is included as the formation of intermediate combustion radicals such as OH, H, O, HO 2 , and H 2 O 2 is essential for accurate predictions of non-equilibrium phenomena such as ignition and extinction. Since the chemical kinetics of H 2 and CH 2 O are the fundamental building blocks of any hydrocarbon oxidation, the inclusion of detailed kinetic mechanisms for CH 2 O and H 2 oxidation enables the reduced mechanism to predict over a wide range of operating conditions provided the reaction rate parameters of fuel-decomposition reaction is optimized over those conditions. Therefore, the rate coefficients for the fuel-decomposition step are estimated and optimized for the ignition delay time measurements of CH 4 , H 2 , CH 4 /H 2, CH 4 /CO and CO/H 2 mixtures available in the literature over a wide range of pressures, temperatures and equivalence ratios that are relevant to gas turbine operating conditions. The optimized reduced mechanism, consisting of 15 species and around 40 reactions, is able to predict the ignition delay time and laminar flame speed measurements of CH 4 , H 2 , CH 4 /H 2 , CH 4 /CO and CO/H 2 mixtures fairly well over a wide range conditions. The model predictions are also compared with that of GRI3.0 mechanism. The reduced kinetic mechanism predicts the ignition delay time of CH 4 and CH 4 /H 2 mixtures far better than GRI mechanism at higher pressures. To demonstrate the predictive capability of the model in reactive flow systems, the reduced mechanism was implemented in Star-CD/KINetics commercial code using a RANS turbulence model to simulate CH 4 /air premixed combustion in a backward facing step. The CFD model predictions of the stable species in the exhaust gas agree well with the GRI mechanism predictions in a chemical reactor network modeling by approximating the backward facing step with a series of perfectly-stirred reactor and plug-flow reactor. INTRODUCTION The production of syngas and H 2 -enriched fuels from Integrated Gasification Combined Cycles (IGCC) technology has become economically and environmentally feasible due to increased energy cost in recent times. Although the term &apos;syngas&apos; refers to a fuel mixture of CO and H 2 , many of the H 2 -enriched fuels from IGCC consists of mainly CO, H 2 , CH 4 and N 2 and trace amount of COS, H 2 S and NH 3 . Moreover, the composition of H 2 -enriched fuel mixtures varies widely; for example, the methane composition in the fuel mixtures can vary from 6.5 to 65 mole

Designing a valid randomized pragmatic primary care implementation trial: the my own health report (MOHR) project

BACKGROUND: There is a pressing need for greater attention to patient-centered health behavior and psychosocial issues in primary care, and for practical tools, study designs and results of clinical and policy relevance. Our goal is to design a scientifically rigorous and valid pragmatic trial to test whether primary care practices can systematically implement the collection of patient-reported information and provide patients needed advice, goal setting, and counseling in response. METHODS: This manuscript reports on the iterative design of the My Own Health Report (MOHR) study, a cluster randomized delayed intervention trial. Nine pairs of diverse primary care practices will be randomized to early or delayed intervention four months later. The intervention consists of fielding the MOHR assessment – addresses 10 domains of health behaviors and psychosocial issues – and subsequent provision of needed counseling and support for patients presenting for wellness or chronic care. As a pragmatic participatory trial, stakeholder groups including practice partners and patients have been engaged throughout the study design to account for local resources and characteristics. Participatory tasks include identifying MOHR assessment content, refining the study design, providing input on outcomes measures, and designing the implementation workflow. Study outcomes include the intervention reach (percent of patients offered and completing the MOHR assessment), effectiveness (patients reporting being asked about topics, setting change goals, and receiving assistance in early versus delayed intervention practices), contextual factors influencing outcomes, and intervention costs. DISCUSSION: The MOHR study shows how a participatory design can be used to promote the consistent collection and use of patient-reported health behavior and psychosocial assessments in a broad range of primary care settings. While pragmatic in nature, the study design will allow valid comparisons to answer the posed research question, and findings will be broadly generalizable to a range of primary care settings. Per the pragmatic explanatory continuum indicator summary (PRECIS) framework, the study design is substantially more pragmatic than other published trials. The methods and findings should be of interest to researchers, practitioners, and policy makers attempting to make healthcare more patient-centered and relevant. TRIAL REGISTRATION: Clinicaltrials.gov: NCT0182574

Simultaneous generation of many RNA-seq libraries in a single reaction

Although RNA-seq is a powerful tool, the considerable time and cost associated with library construction has limited its utilization for various applications. RNAtag-Seq, an approach to generate multiple RNA-seq libraries in a single reaction, lowers time and cost per sample, and it produces data on prokaryotic and eukaryotic samples that are comparable to those generated by traditional strand-specific RNA-seq approaches

Design and acceptability assessment of a new reversible orthosis

We present a new device aimed at being used for upper limb rehabilitation. Our main focus was to design a robot capable of working in both the passive mode (i.e. the robot shall be strong enough to generate human-like movements while guiding the weak arm of a patient) and the active mode (i.e. the robot shall be able of following the arm without disturbing human natural motion). This greatly challenges the design, since the system shall be reversible and lightweight while providing human compatible strength, workspace and speed. The solution takes the form of an orthotic structure, which allows control of human arm redundancy contrarily to clinically available upper limb rehabilitation robots. It is equipped with an innovative transmission technology, which provides both high gear ratio and fine reversibility. In order to evaluate the device and its therapeutic efficacy, we compared several series of pointing movements in healthy subjects wearing and not wearing the orthotic device . In this way, we could assess any disturbing effect on normal movements. Results show that the main movement characteristics (direction, duration, bell shape profile) are preserved. ©2008 IEEE

Some Results on Cubic and Higher Order Extensions of the Poincar\'e Algebra

In these lectures we study some possible higher order (of degree greater than two) extensions of the Poincar\'e algebra. We first give some general properties of Lie superalgebras with some emphasis on the supersymmetric extension of the Poincar\'e algebra or Supersymmetry. Some general features on the so-called Wess-Zumino model (the simplest field theory invariant under Supersymmetry) are then given. We further introduce an additional algebraic structure called Lie algebras of order F, which naturally comprise the concepts of ordinary Lie algebras and superalgebras. This structure enables us to define various non-trivial extensions of the Poincar\'e algebra. These extensions are studied more precisely in two different contexts. The first algebra we are considering is shown to be an (infinite dimensional) higher order extension of the Poincar\'e algebra in $(1+2)-$dimensions and turns out to induce a symmetry which connects relativistic anyons. The second extension we are studying is related to a specific finite dimensional Lie algebra of order three, which is a cubic extension of the Poincar\'e algebra in $D-$space-time dimensions. Invariant Lagrangians are constructed.Comment: Mini course given at the Workshop higher symmetries in physics, Madrid, Spain, November 6-8, 200

No major flaws in "Identification of individuals by trait prediction using whole-genome sequencing data"

In a recently published PNAS article, we studied the identifiability of genomic samples using machine learning methods [Lippert et al., 2017]. In a response, Erlich [2017] argued that our work contained major flaws. The main technical critique of Erlich [2017] builds on a simulation experiment that shows that our proposed algorithm, which uses only a genomic sample for identification, performed no better than a strategy that uses demographic variables. Below, we show why this comparison is misleading and provide a detailed discussion of the key critical points in our analyses that have been brought up in Erlich [2017] and in the media. Further, not only faces may be derived from DNA, but a wide range of phenotypes and demographic variables. In this light, the main contribution of Lippert et al. [2017] is an algorithm that identifies genomes of individuals by combining multiple DNA-based predictive models for a myriad of traits