Amyloid precursor protein cleavage-dependent and -independent axonal degeneration programs share a common nicotinamide mononucleotide adenylyltransferase 1-sensitive pathway

Axonal degeneration is a hallmark of many debilitating neurological disorders and is thought to be regulated by mechanisms distinct from those governing cell body death. Recently, caspase 6 activation via APP cleavage and activation of DR6 was discovered to induce axon degeneration after NGF withdrawal. We tested whether this pathway is involved in axonal degeneration caused by withdrawal of other trophic support, axotomy or vincristine exposure. Neurturin deprivation, like NGF withdrawal activated this APP/DR6/caspase 6 pathway and resulted in axonal degeneration, however, APP cleavage and caspase 6 activation were not involved in axonal degeneration induced by mechanical or toxic insults. However, loss of surface APP (sAPP) and caspase 6 activation were observed during axonal degeneration induced by dynactin 1(Dctn1) dysfunction, which disrupts axonal transport. Mutations in Dctn1 are associated with motor neuron disease and frontal temporal dementia, thus suggesting that the APP/caspase 6 pathway could be important in specific types of disease-associated axonal degeneration. The NGF deprivation paradigm, with its defined molecular pathway, was used to examine the context of Nmnat-mediated axonal protection. We found that although Nmnat blocks axonal degeneration after trophic factor withdrawal, it did not prevent loss of axon sAPP or caspase 6 activation within the axon, suggesting it acts downstream of caspase 6. These results indicate that diverse insults induce axonal degeneration via multiple pathways and that these degeneration signals converge on a common, Nmnat-sensitive program that is uniquely involved in axonal, but not cell body, degeneration

Prospects For Identifying Dark Matter With CoGeNT

It has previously been shown that the excess of events reported by the CoGeNT collaboration could be generated by elastically scattering dark matter particles with a mass of approximately 5-15 GeV. This mass range is very similar to that required to generate the annual modulation observed by DAMA/LIBRA and the gamma rays from the region surrounding the Galactic Center identified within the data of the Fermi Gamma Ray Space Telescope. To confidently conclude that CoGeNT's excess is the result of dark matter, however, further data will likely be needed. In this paper, we make projections for the first full year of CoGeNT data, and for its planned upgrade. Not only will this body of data more accurately constrain the spectrum of nuclear recoil events, and corresponding dark matter parameter space, but will also make it possible to identify seasonal variations in the rate. In particular, if the CoGeNT excess is the product of dark matter, then one year of CoGeNT data will likely reveal an annual modulation with a significance of 2-3$\sigma$. The planned CoGeNT upgrade will not only detect such an annual modulation with high significance, but will be capable of measuring the energy spectrum of the modulation amplitude. These measurements will be essential to irrefutably confirming a dark matter origin of these events.Comment: 6 pages, 6 figure

CoGeNT Interpretations

Recently, the CoGeNT experiment has reported events in excess of expected background. We analyze dark matter scenarios which can potentially explain this signal. Under the standard case of spin independent scattering with equal couplings to protons and neutrons, we find significant tensions with existing constraints. Consistency with these limits is possible if a large fraction of the putative signal events is coming from an additional source of experimental background. In this case, dark matter recoils cannot be said to explain the excess, but are consistent with it. We also investigate modifications to dark matter scattering that can evade the null experiments. In particular, we explore generalized spin independent couplings to protons and neutrons, spin dependent couplings, momentum dependent scattering, and inelastic interactions. We find that some of these generalizations can explain most of the CoGeNT events without violation of other constraints. Generalized couplings with some momentum dependence, allows further consistency with the DAMA modulation signal, realizing a scenario where both CoGeNT and DAMA signals are coming from dark matter. A model with dark matter interacting and annihilating into a new light boson can realize most of the scenarios considered.Comment: 24 pages, 12 figs, v2: published version, some discussions clarifie

Predictive biometrics: A review and analysis of predicting personal characteristics from biometric data

Interest in the exploitation of soft biometrics information has continued to develop over the last decade or so. In comparison with traditional biometrics, which focuses principally on person identification, the idea of soft biometrics processing is to study the utilisation of more general information regarding a system user, which is not necessarily unique. There are increasing indications that this type of data will have great value in providing complementary information for user authentication. However, the authors have also seen a growing interest in broadening the predictive capabilities of biometric data, encompassing both easily definable characteristics such as subject age and, most recently, `higher level' characteristics such as emotional or mental states. This study will present a selective review of the predictive capabilities, in the widest sense, of biometric data processing, providing an analysis of the key issues still adequately to be addressed if this concept of predictive biometrics is to be fully exploited in the future

Dark Matter attempts for CoGeNT and DAMA

Recently, the CoGeNT collaboration presented a positive signal for an annual modulation in their data set. In light of the long standing annual modulation signal in DAMA/LIBRA, we analyze the compatibility of both of these signal within the hypothesis of dark matter (DM) scattering on nuclei, taking into account existing experimental constraints. We consider the cases of elastic and inelastic scattering with either spin-dependent or spin-independent coupling to nucleons. We allow for isospin violating interactions as well as for light mediators. We find that there is some tension between the size of the modulation signal and the time-integrated event excess in CoGeNT, making it difficult to explain both simultaneously. Moreover, within the wide range of DM interaction models considered, we do not find a simultaneous explanation of CoGeNT and DAMA/LIBRA compatible with constraints from other experiments. However, in certain cases part of the data can be made consistent. For example, the modulation signal from CoGeNT becomes consistent with the total rate and with limits from other DM searches at 90% CL (but not with the DAMA/LIBRA signal) if DM scattering is inelastic spin-independent with just the right couplings to protons and neutrons to reduce the scattering rate on xenon. Conversely the DAMA/LIBRA signal (but not CoGeNT) can be explained by spin-dependent inelastic DM scattering.Comment: 20 pages, 9 figure

Hawking Temperature in Taub-NUT (A)dS spaces via the Generalized Uncertainty Principle

Using the extended forms of the Heisenberg uncertainty principle from string theory and the quantum gravity theory, we drived Hawking temperature of a Taub-Nut-(A)dS black hole. In spite of their distinctive natures such as asymptotically locally flat and breakdown of the area theorem of the horizon for the black holes, we show that the corrections to Hawking temperature by the generalized versions of the the Heisenberg uncertainty principle increases like the Schwarzschild-(A)dS black hole and give the reason why the Taub-Nut-(A)dS metric may have AdS/CFT dual picture.Comment: version published in General Relativity and Gravitatio

The dynamics of genome replication using deep sequencing

Peer reviewedPublisher PD

Blocking Effect of an Immuno-Suppressive Agent, Cynarin, on CD28 of T-Cell Receptor

Purpose: Cynarin, a potential immunosuppressant that blocks the interaction between the CD28 of T-cell receptor and CD80 of antigen presenting cells, was found in Echinacea purpurea by a new pharmaceutical screening method: After Flowing Through Immobilized Receptor (AFTIR; Dong et al., J Med Chem, 49:1845-1854, 2006). This Echinacea component is the first small molecule that is able to specifically block "signal 2" of T-cell activation. Methods: In this study, we used the AFTIR method to further confirm that cynarin effectively blocked the binding between CD80 of B-cells and CD28 of T-cells, and provide details of its mechanism of action. Results: The experimental results showed that cynarin blocked about 87% of the CD28-dependent "signal 2" pathway of T-cell activation under the condition of one to one ratio of T-cell and B-cell in vitro. Theoretical structure modeling showed that cynarin binds to the "G-pocket" of CD28 (Evans et al., Nat Immunol, 6:271-279, 2005), and thus interrupts the site of interaction between CD28 and CD80. Conclusions: These results confirm both that AFTIR is a promising method for screening selective active compounds from herbal medicine and that cynarin has great potential as an immuno-suppressive agent

Enhancing the Social Capital of Learning Communities by Using an Ad Hoc Transient Communities Service

Fetter, S., Berlanga, A. J., & Sloep, P. B. (2009). Enhancing the Social Capital of Learning Communities by Using an Ad Hoc Transient Communities Service. In M. Spaniol, Q. Li, R. Klamma & R. W. H. Lau (Eds.), Proceedings of the 8th International Conference Advances in Web-based Learning - ICWL 2009 (pp. 150-157). August, 19-21, 2009, Aachen, Germany. Lecture Notes in Computer Science 5686; Berlin, Heidelberg: Springer-Verlag.In online learning, communities can help to enhance learning. However, because of the dynamic nature of communities, attaining and sustaining these communities can be difficult. One aspect that has an influence on, and is influenced by these dynamics is the social capital of a community. Features of social capital are the social network structure, the sense of belonging and, the support received and provided. It is hypothesized that these features can be improved by using Ad Hoc Transient Communities (AHTCs). Through an AHTC learners are brought together for a specific, learning-related goal (‘ad hoc’) and for only a limited amount of time (‘transience’). To test whether the use of AHTCs has a positive influence on the social capital, a learner support service which enables the use of AHTCs is proposed. Furthermore, requirements, pre-requisites, and future research are discussed.The work on this publication has been sponsored by the TENCompetence Integrated Project that is funded by the European Commission's 6th Framework Programme, priority IST/Technology Enhanced Learning. Contract 027087 [http://www.tencompetence.org