Telomere length regulation: coupling DNA end processing to feedback regulation of telomerase

The conventional DNA polymerase machinery is unable to fully replicate the ends of linear chromosomes. To surmount this problem, nearly all eukaryotes use the telomerase enzyme, a specialized reverse transcriptase that utizes its own RNA template to add short TG-rich repeats to chromosome ends, thus reversing their gradual erosion occurring at each round of replication. This unique, non-DNA templated mode of telomere replication requires a regulatory mechanism to ensure that telomerase acts at telomeres whose TG tracts are too short, but not at those with long tracts, thus maintaining the protective TG repeat cap at an appropriate average length. The prevailing notion in the field is that telomere length regulation is brought about through a negative feedback mechanism that counts TG repeat-bound protein complexes to generate a signal that regulates telomerase action. This review summarizes experiments leading up to this model and then focuses on more recent experiments, primarily from yeast, that begin to suggest how this counting mechanism might work. The emerging picture is that of a complex interplay between the conventional DNA replication machinery, DNA damage response factors, and a specialized set of proteins that help to recruit and regulate the telomerase enzyme

Proposal for a Performance Dashboard for the Monitoringof Water and Sewage Service Companies (WaSCs)

The water and sewage industry provides an essential service to the community, but it is characterized by natural monopoly tendencies of service suppliers. In this framework, it is very important to assist regulators with a small set of critical indicators (performance dashboard) for the evaluation and monitoring of the service provided by Water and Sewage Companies (WaSCs). The paper originates from the analysis of situation of Piemonte (Italy), where each regional and local body adopts a proprietary Performance Measurement System (PMS). In order to improve the coordination of information flow and to support the definition of common service standards, a methodology to merge existing PMSs and define a unique shared reference system is proposed. The Kaplan and Norton's Balanced Scorecard (BSC) is adopted as the reference model of this approach. BSC is widely recognized to be an exhaustive and balanced framework in describing the performances of an organization and ensures that all the operational aspects of WaSCs are adequately monitored. The output of the proposed procedure is a general performance dashboard for the monitoring of WaSCs. The dashboard is shown and some remarks about indicators properties are developed. In particular, this analysis highlights some common pitfalls originated by a ‘rushed' aggregation of several performance indicators. Description is supported by several example

Note on New KLT relations

In this short note, we present two results about KLT relations discussed in recent several papers. Our first result is the re-derivation of Mason-Skinner MHV amplitude by applying the S_{n-3} permutation symmetric KLT relations directly to MHV amplitude. Our second result is the equivalence proof of the newly discovered S_{n-2} permutation symmetric KLT relations and the well-known S_{n-3} permutation symmetric KLT relations. Although both formulas have been shown to be correct by BCFW recursion relations, our result is the first direct check using the regularized definition of the new formula.Comment: 15 Pages; v2: minor correction

Disentangling Fun and Enjoyment in Exergames Using an Expanded Design, Play, Experience Framework: A Narrative Review

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Can disordered mobile phone use be considered a behavioral addiction? An update on current evidence and a comprehensive model for future research

Despite the many positive outcomes, excessive mobile phone use is now often associated with potentially harmful and/or disturbing behaviors (e.g., symptoms of deregulated use, negative impact on various aspects of daily life such as relationship problems, and work intrusion). Problematic mobile phone use (PMPU) has generally been considered as a behavioral addiction that shares many features with more established drug addictions. In light of the most recent data, the current paper reviews the validity of the behavioral addiction model when applied to PMPU. On the whole, it is argued that the evidence supporting PMPU as an addictive behavior is scarce. In particular, it lacks studies that definitively show behavioral and neurobiological similarities between mobile phone addiction and other types of legitimate addictive behaviors. Given this context, an integrative pathway model is proposed that aims to provide a theoretical framework to guide future research in the field of PMPU. This model highlights that PMPU is a heterogeneous and multi-faceted condition

Higher-Spin Interactions: four-point functions and beyond

In this work we construct an infinite class of four-point functions for massless higher-spin fields in flat space that are consistent with the gauge symmetry. In the Lagrangian picture, these reflect themselves in a peculiar non-local nature of the corresponding non-abelian higher-spin couplings implied by the Noether procedure that starts from the fourth order. We also comment on the nature of the colored spin-2 excitation present both in the open string spectrum and in the Vasiliev system, highlighting how some aspects of String Theory appear to reflect key properties of Field Theory that go beyond its low energy limit. A generalization of these results to n-point functions, fermions and mixed-symmetry fields is also addressed.Comment: 66 pages, 10 figures, 1 table, LaTex. Several statements clarified. Final version to appear in JHE

A Kernel to Exploit Informative Missingness in Multivariate Time Series from EHRs

A large fraction of the electronic health records (EHRs) consists of clinical measurements collected over time, such as lab tests and vital signs, which provide important information about a patient's health status. These sequences of clinical measurements are naturally represented as time series, characterized by multiple variables and large amounts of missing data, which complicate the analysis. In this work, we propose a novel kernel which is capable of exploiting both the information from the observed values as well the information hidden in the missing patterns in multivariate time series (MTS) originating e.g. from EHRs. The kernel, called TCK$_{IM}$, is designed using an ensemble learning strategy in which the base models are novel mixed mode Bayesian mixture models which can effectively exploit informative missingness without having to resort to imputation methods. Moreover, the ensemble approach ensures robustness to hyperparameters and therefore TCK$_{IM}$ is particularly well suited if there is a lack of labels - a known challenge in medical applications. Experiments on three real-world clinical datasets demonstrate the effectiveness of the proposed kernel.Comment: 2020 International Workshop on Health Intelligence, AAAI-20. arXiv admin note: text overlap with arXiv:1907.0525

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote