Scalable Similarity Search for Molecular Descriptors

Similarity search over chemical compound databases is a fundamental task in the discovery and design of novel drug-like molecules. Such databases often encode molecules as non-negative integer vectors, called molecular descriptors, which represent rich information on various molecular properties. While there exist efficient indexing structures for searching databases of binary vectors, solutions for more general integer vectors are in their infancy. In this paper we present a time- and space- efficient index for the problem that we call the succinct intervals-splitting tree algorithm for molecular descriptors (SITAd). Our approach extends efficient methods for binary-vector databases, and uses ideas from succinct data structures. Our experiments, on a large database of over 40 million compounds, show SITAd significantly outperforms alternative approaches in practice.Comment: To be appeared in the Proceedings of SISAP'1

Positive psychology of Malaysian students: impacts of engagement, motivation, self-compassion and wellbeing on mental health

Malaysia plays a key role in education of the Asia Pacific, expanding its scholarly output rapidly. However, mental health of Malaysian students is challenging, and their help-seeking is low because of stigma. This study explored the relationships between mental health and positive psychological constructs (academic engagement, motivation, self-compassion, and wellbeing), and evaluated the relative contribution of each positive psychological construct to mental health in Malaysian students. An opportunity sample of 153 students completed the measures regarding these constructs. Correlation, regression, and mediation analyses were conducted. Engagement, amotivation, self-compassion, and wellbeing were associated with, and predicted large variance in mental health. Self-compassion was the strongest independent predictor of mental health among all the positive psychological constructs. Findings can imply the strong links between mental health and positive psychology, especially selfcompassion. Moreover, intervention studies to examine the effects of self-compassion training on mental health of Malaysian students appear to be warranted.N/

Fast and easy blind deblurring using an inverse filter and PROBE

PROBE (Progressive Removal of Blur Residual) is a recursive framework for blind deblurring. Using the elementary modified inverse filter at its core, PROBE's experimental performance meets or exceeds the state of the art, both visually and quantitatively. Remarkably, PROBE lends itself to analysis that reveals its convergence properties. PROBE is motivated by recent ideas on progressive blind deblurring, but breaks away from previous research by its simplicity, speed, performance and potential for analysis. PROBE is neither a functional minimization approach, nor an open-loop sequential method (blur kernel estimation followed by non-blind deblurring). PROBE is a feedback scheme, deriving its unique strength from the closed-loop architecture rather than from the accuracy of its algorithmic components

Understanding how children are coping with climate change anxiety by exploring coping strategies and supportive interventions.

Climate change presents a significant threat to both the planet and human prosperity which impacts our physical health and mental well-being. There is an imminent requirement for significant global action. This means (a) our children have been born into unprecedented times and (b) as future adults, they will find themselves facing the major consequences of climate change. These can negatively affect their mental health and well-being. This paper reports the effect of climate anxiety on this population group through an exploration of coping strategies and supportive interventions. Empowering children to engage in climate action has been identified as a coping strategy. Whilst equipping them with knowledge and resources on climate change and providing safe spaces and experiences in nature are identified as supportive interventions. However, further empirical research evidence is needed to determine the next steps to address the extent of the impact of climate anxiety and prepare our children for the future

Ontological addiction theory: attachment to me, mine, and I

Background: Ontological addiction theory (OAT) is a novel metaphysical model of psychopathology and posits that human beings are prone to forming implausible beliefs concerning the way they think they exist, and that these beliefs can become addictive leading to functional impairments and mental illness. The theoretical underpinnings of OAT derive from the Buddhist philosophical perspective that all phenomena, including the self, do not manifest inherently or independently. Aims and methods: This paper outlines the theoretical foundations of OAT along with indicative supportive empirical evidence from studies evaluating meditation awareness training as well as studies investigating non-attachment, emptiness, compassion, and loving-kindness. Results: OAT provides a novel perspective on addiction, the factors that underlie mental illness, and how beliefs concerning selfhood are shaped and reified. Conclusion: In addition to continuing to test the underlying assumptions of OAT, future empirical research needs to determine how ontological addiction fits with extant theories of self, reality, and suffering, as well with more established models of addiction

The optical depth of the Universe to ultrahigh energy cosmic ray scattering in the magnetized large scale structure

This paper provides an analytical description of the transport of ultrahigh energy cosmic rays in an inhomogeneously magnetized intergalactic medium. This latter is modeled as a collection of magnetized scattering centers such as radio cocoons, magnetized galactic winds, clusters or magnetized filaments of large scale structure, with negligible magnetic fields in between. Magnetic deflection is no longer a continuous process, it is rather dominated by scattering events. We study the interaction between high energy cosmic rays and the scattering agents. We then compute the optical depth of the Universe to cosmic ray scattering and discuss the phenomological consequences for various source scenarios. For typical parameters of the scattering centers, the optical depth is greater than unity at 5x10^{19}eV, but the total angular deflection is smaller than unity. One important consequence of this scenario is the possibility that the last scattering center encountered by a cosmic ray be mistaken with the source of this cosmic ray. In particular, we suggest that part of the correlation recently reported by the Pierre Auger Observatory may be affected by such delusion: this experiment may be observing in part the last scattering surface of ultrahigh energy cosmic rays rather than their source population. Since the optical depth falls rapidly with increasing energy, one should probe the arrival directions of the highest energy events beyond 10^{20}eV on an event by event basis to circumvent this effect.Comment: version to appear in PRD; substantial improvements: extended introduction, sections added on angular images and on direction dependent effects with sky maps of optical depth, enlarged discussion of Auger results (conclusions unchanged); 27 pages, 9 figure

Cationic siRNAs Provide Carrier-Free Gene Silencing in Animal Cells

siRNA-mediated gene silencing requires intracellular delivery of the nucleic acid. We have developed a carrierless molecular approach that follows the same cell entry route as cationic supramolecular complexes, yet should avoid the extracellular barriers encountered by nanoparticles. Cationic oligospermine−oligonucleotide conjugates (ZNAs, for Zip Nucleic Acids) were synthesized stepwise on an oligonucleotide synthesizer using a DMT-spermine phosphoramidite derivative. They were shown to enter cells and have access to the cytoplasm, provided their formal charge ratio N/P was >1.5. Cationic siRNAs that fulfilled this condition were shown to achieve selective inhibition of luciferase gene expression in the submicromolar concentration range in constitutively luciferase-expressing cells

Oligonucleotide−Oligospermine Conjugates (Zip Nucleic Acids): A Convenient Means of Finely Tuning Hybridization Temperatures

Synthesis of oligonucleotide probes and control of their hybridization temperature are key aspects of polymerase chain reaction (PCR)-based detection of genetic sequences. A straightforward means to approach the last goal is to decrease the repulsion between the polyanionic probe and target strands. To this end, we have developed a versatile automated synthesis of oligonucleotide−oligospermine derivatives that gave fast access to a large variety of compounds. Plots of their hybridization temperatures Tm vs overall charge provided a measure of the impact of interstrand phosphate repulsion (and of spermine-mediated attraction) on the main driving force of duplex formation, i.e., base pairing. It showed that stabilization brought about by excess cationic charges can be of larger absolute magnitude than interstrand repulsion, even in high salt media. Base sequence and conjugation site (3′ or 5′) hardly influenced the effect of spermine on Tm. In typical PCR probe conditions, the Tm increased linearly with the number of grafted spermines (e.g., 6.2 °C per spermine for a decanucleotide probe). The large data set of Tm vs number of spermines and oligonucleotide length allowed us to empirically derive a simple mathematical relation that is accurately predicting the Tm of any oligonucleotide−oligospermine derivative. Zip nucleic acids (ZNA) are thus providing an interesting alternative to locked nucleic acids (LNA) or minor groove binders (MGB) for raising the stability of 8−12-mer oligonucleotides up to ca. 70 °C, the level required for quantitative PCR experiments