On CPT Symmetry: Cosmological, Quantum-Gravitational and other possible violations and their phenomenology

I discuss various ways in which CPT symmetry may be violated, and their phenomenology in current or immediate future experimental facilities, both terrestrial and astrophysical. Specifically, I discuss first violations of CPT symmetry due to the impossibility of defining a scattering matrix as a consequence of the existence of microscopic or macroscopic space-time boundaries, such as Planck-scale Black-Hole (event) horizons, or cosmological horizons due to the presence of a (positive) cosmological constant in the Universe. Second, I discuss CPT violation due to breaking of Lorentz symmetry, which may characterize certain approaches to quantum gravity, and third, I describe models of CPT non invariance due to violations of locality of interactions. In each of the above categories I discuss experimental sensitivities. I argue that the majority of Lorentz-violating cases of CPT breaking, with minimal (linear) suppression by the Planck-mass scale, are already excluded by current experimental tests. There are however some (stringy) models which can evade these constraints.Comment: 27 pages latex, Conference talk Beyond the Desert 200

Mass extinctions and supernova explosions

A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be excluded and might even have been responsible for past extinction events.Comment: Chapter for forthcoming book: Handbook of Supernovae, P. Murdin and A. Alsabeti (eds.), Springer International Publishing (in press

On SUSY GUTs with a degenerate Higgs mass matrix

Certain supersymmetric grand unified models predict that the coefficients of the quadratic terms in the MSSM Higgs potential should be degenerate at the GUT scale. We discuss some examples for such models, and we analyse the implications of this peculiar condition of a GUT-scale degenerate Higgs mass matrix for low-scale MSSM phenomenology. To this end we explore the parameter space which is consistent with existing experimental constraints by means of a Markov Chain Monte Carlo analysis.Comment: 31 pages, 27 figures; v2: typos correcte

Challenges of Profile Likelihood Evaluation in Multi-Dimensional SUSY Scans

Statistical inference of the fundamental parameters of supersymmetric theories is a challenging and active endeavor. Several sophisticated algorithms have been employed to this end. While Markov-Chain Monte Carlo (MCMC) and nested sampling techniques are geared towards Bayesian inference, they have also been used to estimate frequentist confidence intervals based on the profile likelihood ratio. We investigate the performance and appropriate configuration of MultiNest, a nested sampling based algorithm, when used for profile likelihood-based analyses both on toy models and on the parameter space of the Constrained MSSM. We find that while the standard configuration is appropriate for an accurate reconstruction of the Bayesian posterior, the profile likelihood is poorly approximated. We identify a more appropriate MultiNest configuration for profile likelihood analyses, which gives an excellent exploration of the profile likelihood (albeit at a larger computational cost), including the identification of the global maximum likelihood value. We conclude that with the appropriate configuration MultiNest is a suitable tool for profile likelihood studies, indicating previous claims to the contrary are not well founded.Comment: 21 pages, 9 figures, 1 table; minor changes following referee report. Matches version accepted by JHE

A Profile Likelihood Analysis of the Constrained MSSM with Genetic Algorithms

The Constrained Minimal Supersymmetric Standard Model (CMSSM) is one of the simplest and most widely-studied supersymmetric extensions to the standard model of particle physics. Nevertheless, current data do not sufficiently constrain the model parameters in a way completely independent of priors, statistical measures and scanning techniques. We present a new technique for scanning supersymmetric parameter spaces, optimised for frequentist profile likelihood analyses and based on Genetic Algorithms. We apply this technique to the CMSSM, taking into account existing collider and cosmological data in our global fit. We compare our method to the MultiNest algorithm, an efficient Bayesian technique, paying particular attention to the best-fit points and implications for particle masses at the LHC and dark matter searches. Our global best-fit point lies in the focus point region. We find many high-likelihood points in both the stau co-annihilation and focus point regions, including a previously neglected section of the co-annihilation region at large m_0. We show that there are many high-likelihood points in the CMSSM parameter space commonly missed by existing scanning techniques, especially at high masses. This has a significant influence on the derived confidence regions for parameters and observables, and can dramatically change the entire statistical inference of such scans.Comment: 47 pages, 8 figures; Fig. 8, Table 7 and more discussions added to Sec. 3.4.2 in response to referee's comments; accepted for publication in JHE

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. <p/>Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. <p/>Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Fluids in cosmology

We review the role of fluids in cosmology by first introducing them in General Relativity and then by applying them to a FRW Universe's model. We describe how relativistic and non-relativistic components evolve in the background dynamics. We also introduce scalar fields to show that they are able to yield an inflationary dynamics at very early times (inflation) and late times (quintessence). Then, we proceed to study the thermodynamical properties of the fluids and, lastly, its perturbed kinematics. We make emphasis in the constrictions of parameters by recent cosmological probes.Comment: 34 pages, 4 figures, version accepted as invited review to the book "Computational and Experimental Fluid Mechanics with Applications to Physics, Engineering and the Environment". Version 2: typos corrected and references expande

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours

Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, is thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of MRT by combining phylogenetic analyses and single-cell mRNA studies in patient-derived organoids. Comparison of somatic mutations shared between cancer and surrounding normal tissues places MRT in a lineage with neural crest-derived Schwann cells. Single-cell mRNA readouts of MRT differentiation, which we examine by reverting the genetic driver mutation underpinning MRT, SMARCB1 loss, suggest that cells are blocked en route to differentiating into mesenchyme. Quantitative transcriptional predictions indicate that combined HDAC and mTOR inhibition mimic MRT differentiation, which we confirm experimentally. Our study defines the developmental block of MRT and reveals potential differentiation therapies

Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior

Microenvironments of biological cells are dominated in vivo by macromolecular crowding and resultant excluded volume effects. This feature is absent in dilute in vitro cell culture. Here, we induced macromolecular crowding in vitro by using synthetic macromolecular globules of nm-scale radius at physiological levels of fractional volume occupancy. We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and AFM-enabled nanoindentation. Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the intracellular actin cytoskeleton. The resulting cell-matrix reciprocity further affected adhesion, proliferation, and migration behavior of MSCs. Macromolecular crowding can thus aid the design of more physiologically relevant in vitro studies and devices for MSCs and other cells, by increasing the fidelity between materials synthesized by cells in vivo and in vitro