Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review

With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis

MultiMetEval: comparative and multi-objective analysis of genome-scale metabolic models

Comparative metabolic modelling is emerging as a novel field, supported by the development of reliable and standardized approaches for constructing genome-scale metabolic models in high throughput. New software solutions are needed to allow efficient comparative analysis of multiple models in the context of multiple cellular objectives. Here, we present the user-friendly software framework Multi-Metabolic Evaluator (MultiMetEval), built upon SurreyFBA, which allows the user to compose collections of metabolic models that together can be subjected to flux balance analysis. Additionally, MultiMetEval implements functionalities for multi-objective analysis by calculating the Pareto front between two cellular objectives. Using a previously generated dataset of 38 actinobacterial genome-scale metabolic models, we show how these approaches can lead to exciting novel insights. Firstly, after incorporating several pathways for the biosynthesis of natural products into each of these models, comparative flux balance analysis predicted that species like Streptomyces that harbour the highest diversity of secondary metabolite biosynthetic gene clusters in their genomes do not necessarily have the metabolic network topology most suitable for compound overproduction. Secondly, multi-objective analysis of biomass production and natural product biosynthesis in these actinobacteria shows that the well-studied occurrence of discrete metabolic switches during the change of cellular objectives is inherent to their metabolic network architecture. Comparative and multi-objective modelling can lead to insights that could not be obtained by normal flux balance analyses. MultiMetEval provides a powerful platform that makes these analyses straightforward for biologists. Sources and binaries of MultiMetEval are freely available from https://github.com/PiotrZakrzewski/MetEv​al/downloads

Direct determination of the solar neutrino fluxes from solar neutrino data

We determine the solar neutrino fluxes from a global analysis of the solar and terrestrial neutrino data in the framework of three-neutrino mixing. Using a Bayesian approach we reconstruct the posterior probability distribution function for the eight normalization parameters of the solar neutrino fluxes plus the relevant masses and mixing, with and without imposing the luminosity constraint. This is done by means of a Markov Chain Monte Carlo employing the Metropolis-Hastings algorithm. We also describe how these results can be applied to test the predictions of the Standard Solar Models. Our results show that, at present, both models with low and high metallicity can describe the data with good statistical agreement.Comment: 24 pages, 1 table, 7 figures. Acknowledgments correcte

Towards sustainable processing of columbite group minerals: elucidating the relation between dielectric properties and physico-chemical transformations in the mineral phase

Current methodologies for the extraction of tantalum and niobium pose a serious threat to human beings and the environment due to the use of hydrofluoric acid (HF). Niobium and tantalum metal powders and pentoxides are widely used for energy efficient devices and components. However, the current processing methods for niobium and tantalum metals and oxides are energy inefficient. This dichotomy between materials use for energy applications and their inefficient processing is the main motivation for exploring a new methodology for the extraction of these two oxides, investigating the microwave absorption properties of the reaction products formed during the alkali roasting of niobium-tantalum bearing minerals with sodium bicarbonate. The experimental findings from dielectric measurement at elevated temperatures demonstrate an exponential increase in the values of the dielectric properties as a result of the formation of NaNbO3-NaTaO3solid solutions at temperatures above 700 °C. The investigation of the evolution of the dielectric properties during the roasting reaction is a key feature in underpinning the mechanism for designing a new microwave assisted high-temperature process for the selective separation of niobium and tantalum oxides from the remainder mineral crystalline lattice

Searches for Long Lived Neutral Particles

An intriguing possibility for TeV scale physics is the existence of neutral long lived particles (LOLIPs) that subsequently decay into SM states. Such particles are many cases indistinguishable from missing transverse energy (MET) at colliders. We propose new methods to search for these particles using neutrino telescopes. We study their detection prospects, assuming production either at the LHC or through dark matter (DM) annihilations in the Sun and the Earth. We find that the sensitivity for LOLIPs produced at the LHC is limited by luminosity and detection energy thresholds. On the other hand, in the case of DM annihilation into LOLIPs, the sensitivity of neutrino telescopes is promising and may extend beyond the reach of upcoming direct detection experiments. In the context of low scale hidden sectors weakly coupled to the SM, such indirect searches allow to probe couplings as small as 10^-15.Comment: 22 pages, 6 figure

Preserving the impossible: conservation of soft-sediment hominin footprint sites and strategies for three-dimensional digital data capture.

Human footprints provide some of the most publically emotive and tangible evidence of our ancestors. To the scientific community they provide evidence of stature, presence, behaviour and in the case of early hominins potential evidence with respect to the evolution of gait. While rare in the geological record the number of footprint sites has increased in recent years along with the analytical tools available for their study. Many of these sites are at risk from rapid erosion, including the Ileret footprints in northern Kenya which are second only in age to those at Laetoli (Tanzania). Unlithified, soft-sediment footprint sites such these pose a significant geoconservation challenge. In the first part of this paper conservation and preservation options are explored leading to the conclusion that to 'record and digitally rescue' provides the only viable approach. Key to such strategies is the increasing availability of three-dimensional data capture either via optical laser scanning and/or digital photogrammetry. Within the discipline there is a developing schism between those that favour one approach over the other and a requirement from geoconservationists and the scientific community for some form of objective appraisal of these alternatives is necessary. Consequently in the second part of this paper we evaluate these alternative approaches and the role they can play in a 'record and digitally rescue' conservation strategy. Using modern footprint data, digital models created via optical laser scanning are compared to those generated by state-of-the-art photogrammetry. Both methods give comparable although subtly different results. This data is evaluated alongside a review of field deployment issues to provide guidance to the community with respect to the factors which need to be considered in digital conservation of human/hominin footprints

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Large-Theta(13) Perturbation Theory of Neutrino Oscillation for Long-Baseline Experiments

The Cervera et al. formula, the best known approximate formula of neutrino oscillation probability for long-baseline experiments, can be regarded as a second-order perturbative formula with small expansion parameter epsilon \equiv Delta m^2_{21} / Delta m^2_{31} \simeq 0.03 under the assumption s_{13} \simeq epsilon. If theta_{13} is large, as suggested by a candidate nu_{e} event at T2K as well as the recent global analyses, higher order corrections of s_{13} to the formula would be needed for better accuracy. We compute the corrections systematically by formulating a perturbative framework by taking theta_{13} as s_{13} \sim \sqrt{epsilon} \simeq 0.18, which guarantees its validity in a wide range of theta_{13} below the Chooz limit. We show on general ground that the correction terms must be of order epsilon^2. Yet, they nicely fill the mismatch between the approximate and the exact formulas at low energies and relatively long baselines. General theorems are derived which serve for better understanding of delta-dependence of the oscillation probability. Some interesting implications of the large theta_{13} hypothesis are discussed.Comment: Fig.2 added, 23 pages. Matches to the published versio

Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression

Regeneration versus scarring in vertebrate appendages and heart

Injuries to complex human organs, such as the limbs and the heart, result in pathological conditions, for which we often lack adequate treatments. While modern regenerative approaches are based on the transplantation of stem cell-derived cells, natural regeneration in lower vertebrates, such as zebrafish and newts, relies predominantly on the intrinsic plasticity of mature tissues. This property involves local activation of the remaining material at the site of injury to promote cell division, cell migration and complete reproduction of the missing structure. It remains an unresolved question why adult mammals are not equally competent to reactivate morphogenetic programmes. Although organ regeneration depends strongly on the proliferative properties of cells in the injured tissue, it is apparent that various organismic factors, such as innervation, vascularization, hormones, metabolism and the immune system, can affect this process. Here, we focus on a correlation between the regenerative capacity and cellular specialization in the context of functional demands, as illustrated by appendages and heart in diverse vertebrates. Elucidation of the differences between homologous regenerative and non-regenerative tissues from various animal models is essential for understanding the applicability of lessons learned from the study of regenerative biology to clinical strategies for the treatment of injured human organs