PubChem3D: Diversity of shape

<p>Abstract</p> <p>Background</p> <p>The shape diversity of 16.4 million biologically relevant molecules from the PubChem Compound database and their 1.46 billion diverse conformers was explored as a function of molecular volume.</p> <p>Results</p> <p>The diversity of shape space was investigated by determining the shape similarity threshold to achieve a maximum on the count of reference shapes per unit of conformer volume. The rate of growth in shape space, as represented by a decreasing shape similarity threshold, was found to be remarkably smooth as a function of volume. There was no apparent correlation between the count of conformers per unit volume and their diversity, meaning that a single reference shape can describe the shape space of many chemical structures. The ability of a volume to describe the shape space of lesser volumes was also examined. It was shown that a given volume was able to describe 40-70% of the shape diversity of lesser volumes, for the majority of the volume range considered in this study.</p> <p>Conclusion</p> <p>The relative growth of shape diversity as a function of volume and shape similarity is surprisingly uniform. Given the distribution of chemicals in PubChem versus what is theoretically synthetically possible, the results from this analysis should be considered a conservative estimate to the true diversity of shape space.</p

Evaluation of a Bayesian inference network for ligand-based virtual screening

Background Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. Results Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. Conclusion A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening

Some remarks on a new exotic spacetime for time travel by free fall

This work is essentially a review of a new spacetime model with closed causal curves, recently presented in another paper (Class. Quantum Grav. \textbf{35}(16) (2018), 165003). The spacetime at issue is topologically trivial, free of curvature singularities, and even time and space orientable. Besides summarizing previous results on causal geodesics, tidal accelerations and violations of the energy conditions, here redshift/blueshift effects and the Hawking-Ellis classification of the stress-energy tensor are examined.Comment: 17 pages, 9 figures. Submitted as a contribution to the proceedings of "DOMOSCHOOL - International Alpine School of Mathematics and Physics, Domodossola 2018". Possible text overlaps with my previous work arXiv:1803.08214, of which this is essentially a review. Additional results concerning redshift/blueshift effects and the classification of the stress-energy tensor are presented her

Exploring the value of a cyber threat intelligence function in an organization

Organizations can struggle to cope with the rapidly advancing threat landscape. A cyber threat intelligence (CTI) function broadly aims to understand how threats operate to better protect the organization from future attacks. This seems like a natural step to take in hardening security. However, CTI is understood and experienced differently across organizations. To explore the value of this function this study used a qualitative method, guided by the Socio-Technical Framework, to understand how the CTI function is interpreted by organizations in South Africa. Thematic analysis was used to provide an in-depth view of how each organization implemented its CTI function and what benefits and challenges they’ve experienced. Findings show that CTI tasks tend to be more manual and resource-intensive, but these challenges can be resolved through automation. It was noted that only larger organizations seem to have the budget and resources available to implement the CTI function, whereas smaller organizations put more reliance on tools. It was observed that skills for the CTI function can be learned on the job, but that formal education provides a good foundation. The findings illustrate the value the CTI function can provide an organization but also the challenges, thereby enabling other organizations to improve preparation before such a function is adopted

Double-chambered right ventricle in an adult patient diagnosed by transthoracic echocardiography

BACKGROUND: Double-chambered right ventricle is a rare congenital disease frequently misdiagnosed in the adult patient. An anomalous muscle band divides the right ventricle in two cavities causing variable degree of obstruction. Although echocardiography is considered a useful method for the diagnosis of this pathology in children, it has been recognized the transthoracic scanning limitation in adults. CASE PRESENTATION: A 29 year-old patient with double-chambered right ventricle presenting mild exercise intolerance referred for follow up of a known ventricular septal defect in whom a complete diagnosis was obtained based only on transthoracic two dimensional echocardiography without the needing of cardiac catheterization. CONCLUSION: Based on non invasive echocardiographic diagnosis, patient was referred to surgical correction, which was completely successful

Comparing the effectiveness of the 0.018-inch versus the 0.022-inch bracket slot system in orthodontic treatment:study protocol for a randomized controlled trial

BACKGROUND: Edgewise fixed orthodontic appliances are available in two different bracket slot sizes (0.018 and 0.022 inch). Both systems are used by clinicians worldwide with some orthodontists claiming the superiority and clinical advantages of one system over the other. However, the scientific evidence supporting this area is scarce and weak. This leaves the clinician’s choice of bracket slot system to clinical preference. We aim to compare the 0.018-inch and 0.022-inch pre-adjusted bracket slot systems in terms of the effectiveness of orthodontic treatment. METHODS/DESIGN: This is a prospective, multicenter, randomized clinical trial, undertaken in the secondary care hospital environment in the NHS Tayside region of Scotland (United Kingdom). A total of 216 orthodontic patients will be recruited in three centers in secondary care hospitals in NHS Tayside. The participants will be randomly allocated to treatment with either the 0.018-inch or 0.022-inch bracket slot systems (n = 108 for each group) using Victory series™ conventional pre-adjusted bracket systems (3 M Unitek, Monrovia, United States). Baseline records and outcome data collected during and at the end of orthodontic treatment will be assessed. The primary outcome measures will be the duration of orthodontic treatment in the maxillary and mandibular arches. The secondary outcome measures will be the number of scheduled appointments for orthodontic treatment in the maxillary and mandibular arches, treatment outcome using Peer Assessment Rating index (PAR), orthodontically induced inflammatory root resorption (as measured using periapical radiographs) and the patient’s perception of wearing orthodontic appliances. DISCUSSION: The results from the current study will serve as evidence to guide the clinician in deciding whether the difference in bracket slot size has a significant impact on the effectiveness of orthodontic treatment. TRIAL REGISTRATION: Registered with ClinicalTrials.gov on 5 March 2014, registration number: NCT02080338

Fast 3D shape screening of large chemical databases through alignment-recycling

<p>Abstract</p> <p>Background</p> <p>Large chemical databases require fast, efficient, and simple ways of looking for similar structures. Although such tasks are now fairly well resolved for graph-based similarity queries, they remain an issue for 3D approaches, particularly for those based on 3D shape overlays. Inspired by a recent technique developed to compare molecular shapes, we designed a hybrid methodology, alignment-recycling, that enables efficient retrieval and alignment of structures with similar 3D shapes.</p> <p>Results</p> <p>Using a dataset of more than one million PubChem compounds of limited size (< 28 heavy atoms) and flexibility (< 6 rotatable bonds), we obtained a set of a few thousand diverse structures covering entirely the 3D shape space of the conformers of the dataset. Transformation matrices gathered from the overlays between these diverse structures and the 3D conformer dataset allowed us to drastically (100-fold) reduce the CPU time required for shape overlay. The alignment-recycling heuristic produces results consistent with <it>de novo </it>alignment calculation, with better than 80% hit list overlap on average.</p> <p>Conclusion</p> <p>Overlay-based 3D methods are computationally demanding when searching large databases. Alignment-recycling reduces the CPU time to perform shape similarity searches by breaking the alignment problem into three steps: selection of diverse shapes to describe the database shape-space; overlay of the database conformers to the diverse shapes; and non-optimized overlay of query and database conformers using common reference shapes. The precomputation, required by the first two steps, is a significant cost of the method; however, once performed, querying is two orders of magnitude faster. Extensions and variations of this methodology, for example, to handle more flexible and larger small-molecules are discussed.</p

Vitamin D in the general population of young adults with autism in the Faroe Islands

Vitamin D deficiency has been proposed as a possible risk factor for developing autism spectrum disorder (ASD). 25-Hydroxyvitamin D3 (25(OH)D3) levels were examined in a cross-sectional population-based study in the Faroe Islands. The case group consisting of a total population cohort of 40 individuals with ASD (aged 15–24 years) had significantly lower 25(OH)D3 than their 62 typically-developing siblings and their 77 parents, and also significantly lower than 40 healthy age and gender matched comparisons. There was a trend for males having lower 25(OH)D3 than females. Effects of age, month/season of birth, IQ, various subcategories of ASD and Autism Diagnostic Observation Schedule score were also investigated, however, no association was found. The very low 25(OH)D3 in the ASD group suggests some underlying pathogenic mechanism