Inhomogeneous Neutrino Degeneracy and Big Bang Nucleosynthesis

We examine Big Bang nucleosynthesis (BBN) in the case of inhomogenous neutrino degeneracy, in the limit where the fluctuations are sufficiently small on large length scales that the present-day element abundances are homogeneous. We consider two representive cases: degeneracy of the electron neutrino alone, and equal chemical potentials for all three neutrinos. We use a linear programming method to constrain an arbitrary distribution of the chemical potentials. For the current set of (highly-restrictive) limits on the primordial element abundances, homogeneous neutrino degeneracy barely changes the allowed range of the baryon-to-photon ratio. Inhomogeneous degeneracy allows for little change in the lower bound on the baryon-to-photon ratio, but the upper bound in this case can be as large as 1.1 \times 10^{-8} (only electron neutrino degeneracy) or 1.0 \times 10^{-9} (equal degeneracies for all three neutrinos). For the case of inhomogeneous neutrino degeneracy, we show that there is no BBN upper bound on the neutrino energy density, which is bounded in this case only by limits from structure formation and the cosmic microwave background.Comment: 6 pages, no figure

Experimental Control and Characterization of Autophagy in Drosophila

Insects such as the fruit fly Drosophila melanogaster, which fundamentally reorganize their body plan during metamorphosis, make extensive use of autophagy for their normal development and physiology. In the fruit fly, the hepatic/adipose organ known as the fat body accumulates nutrient stores during the larval feeding stage. Upon entering metamorphosis, as well as in response to starvation, these nutrients are mobilized through a massive induction of autophagy, providing support to other tissues and organs during periods of nutrient deprivation. High levels of autophagy are also observed in larval tissues destined for elimination, such as the salivary glands and larval gut. Drosophila is emerging as an important system for studying the functions and regulation of autophagy in an in vivo setting. In this chapter we describe reagents and methods for monitoring autophagy in Drosophila, focusing on the larval fat body. We also describe methods for experimentally activating and inhibiting autophagy in this system and discuss the potential for genetic analysis in Drosophila to identify novel genes involved in autophagy

A note on intersecting hypergraphs with large cover number

Published by 'The Electronic Journal of Combinatorics' at 10.37236/6460.We give a construction of r-partite r-uniform intersecting hypergraphs with cover number at least r−4 for all but finitely many r. This answers a question of Abu-Khazneh, Barát, Pokrovskiy and Szabó, and shows that a long-standing unsolved conjecture due to Ryser is close to being best possible for every value of r.Natural Sciences and Engineering Research Council of Canad

Quantitative magnetic resonance imaging to evaluate patients with liver cirrhosis

Introduction: The incidence and mortality of liver disease is increasing. Most morbidity and mortality in patients with liver cirrhosis results from the development and progression of portal hypertension, characterised by increased intrahepatic resistance and splanchnic vasodilatation. Transjugular hepatic venous pressure gradient (HVPG) is the only validated technique for the assessment of portal pressure to stratify an individual’s risk and changes following therapeutic interventions. However, HVPG measurements are expensive, invasive and only available in specialist centres which precludes the use of HVPG in routine clinical practice. Magnetic Resonance Imaging (MRI) technologies provide unique methods for imaging the whole liver and abdomen. As a result, several favourable characteristics required to stratify chronic liver diseases are obtained. These methodologies are non-invasive, provide objective measurements, are organ-specific and do not use ionising radiation. They measure multiple parameters in a single scan session. Uniquely amongst imaging modalities, it is possible to concordantly assess several different measures in the same scan session. Methodology: All three prospective studies compared non-invasive quantitative MRI measures to current gold-standard measures. In the first part of the thesis, I investigated the effect of field strength on surrogate MR measures of portal pressure. A prospective cross-sectional study of patients undergoing transjugular liver biopsies across two sites recruited participants to attend for a single study visit within 12 weeks. Patients underwent transient elastography, blood tests and a single non-invasive MRI scan at a field strength of 3 Tesla. All measures were compared to HVPG. In the second part of the thesis, I investigated the effects of Direct Acting Antiviral therapy given to patients with advanced liver disease caused by Hepatitis C virus. Patients eligible for treatment were invited to take part in a prospective observational study. Participants underwent an MRI scan before and after treatment completion (within 12 weeks of last tablet swallowed). Patients followed standard management protocols for therapy and monitoring. Routine clinical information including medical history, clinical examination and laboratory values were recorded for each participant and compared to the MRI measures. In the third part of the thesis, I aimed to develop a novel quantitative MRI tool to evaluate increased small bowel permeability in a double-blind, placebo-controlled, healthy volunteer study. Development of bacterial translocation is believed to be a key prognostic event precipitating decompensation and life-threatening complications in patients with advanced chronic liver disease. The best available tools to evaluate gut permeability were compared with a newly developed MRI assessment of the small bowel. Provocation with enteral Indomethacin administration, an accepted positive control for experimental medicine studies, was used to compare the MRI measures to bowel permeability assessed by the Lactulose/Mannitol urinary excretion ratio (LMR). Results: In the first prospective cross-sectional study, 39 patients were recruited who had MRI data for comparison to HVPG. At 3 Tesla, HVPG significantly correlated with: iron corrected liver longitudinal relaxation time (T1: R=0.60, p15 mmHg. In the second prospective observational study of patients undergoing new treatments for chronic Hepatitis C infection, multiparametric MRI, in a time window of 3-6 months between pre- and post-treatment scans, demonstrated changes in hepatic composition in 17 patients. Liver longitudinal relaxation time (T1, 35±4 ms), transverse relaxation time (T2, 2.5±0.8 ms; T2*, 3.0±0.7 ms) and liver perfusion (28.1±19.7ml/100g/min) all significantly reduced. These measures are likely linked to reduced pro-inflammatory milieu, including interstitial oedema, within the liver. By chance, seven patients were diagnosed with hepatocellular carcinoma after starting treatment in whom pre-treatment MRI lesions could be identified on the research scans. In the double-blind placebo-controlled study of 22 healthy volunteers, only a newly developed measure of small bowel T2 significantly increased (70 ± 36 ms vs 115 ± 63ms, p=0.017) and correlated (R=0.68, p<0.01) with increased LMR following indomethacin administration (0.019 (IQR 0.016-0.026) to 0.025 (IQR 0.021-0.039), p=0.002). Conclusions: This thesis provides data that suggests a non-contrast MRI scan may uniquely be able to simultaneously evaluate multiple measures of prognostic importance in patients with chronic liver disease including liver fibrosis, portal pressure, the development of a hyperdynamic circulation, small bowel permeability and hepatocellular carcinoma surveillance. These findings need to be validated, optimised and shown to evaluate efficacy of interventions in order to lead to clinical adoption. MRI has the potential to be a key non-invasive tool to evaluate the efficacy of interventions in chronic liver disease and stratify patients according to the potential clinical outcomes

Effect of multiple reusing of simulated air showers in detector simulations

The study of high energy cosmic rays requires detailed Monte Carlo simulations of both, extensive air showers and the detectors involved in their detection. In particular, the energy calibration of several experiments is obtained from simulations. Also, in composition studies simulations play a fundamental role because the primary mass is determined by comparing experimental with simulated data. At the highest energies the detailed simulation of air showers is very costly in processing time and disk space due to the large number of secondary particles generated in interactions with the atmosphere. Therefore, in order to increase the statistics, it is quite common to recycle single showers many times to simulate the detector response. As a result, the events of the Monte Carlo samples generated in this way are not fully independent. In this work we study the artificial effects introduced by the multiple use of single air showers for the detector simulations. In particular, we study in detail the effects introduced by the repetitions in the kernel density estimators which are frequently used in composition studies.Comment: 15 pages and 4 figure

Exponential Time Complexity of Weighted Counting of Independent Sets

We consider weighted counting of independent sets using a rational weight x: Given a graph with n vertices, count its independent sets such that each set of size k contributes x^k. This is equivalent to computation of the partition function of the lattice gas with hard-core self-repulsion and hard-core pair interaction. We show the following conditional lower bounds: If counting the satisfying assignments of a 3-CNF formula in n variables (#3SAT) needs time 2^{\Omega(n)} (i.e. there is a c>0 such that no algorithm can solve #3SAT in time 2^{cn}), counting the independent sets of size n/3 of an n-vertex graph needs time 2^{\Omega(n)} and weighted counting of independent sets needs time 2^{\Omega(n/log^3 n)} for all rational weights x\neq 0. We have two technical ingredients: The first is a reduction from 3SAT to independent sets that preserves the number of solutions and increases the instance size only by a constant factor. Second, we devise a combination of vertex cloning and path addition. This graph transformation allows us to adapt a recent technique by Dell, Husfeldt, and Wahlen which enables interpolation by a family of reductions, each of which increases the instance size only polylogarithmically.Comment: Introduction revised, differences between versions of counting independent sets stated more precisely, minor improvements. 14 page

Indestructibility of Vopenka's Principle

We show that Vopenka's Principle and Vopenka cardinals are indestructible under reverse Easton forcing iterations of increasingly directed-closed partial orders, without the need for any preparatory forcing. As a consequence, we are able to prove the relative consistency of these large cardinal axioms with a variety of statements known to be independent of ZFC, such as the generalised continuum hypothesis, the existence of a definable well-order of the universe, and the existence of morasses at many cardinals.Comment: 15 pages, submitted to Israel Journal of Mathematic

Electronic structure and ferroelectricity in SrBi2Ta2O9

The electronic structure of SrBi2Ta2O9 is investigated from first-principles, within the local density approximation, using the full-potential linearized augmented plane wave (LAPW) method. The results show that, besides the large Ta(5d)-O(2p) hybridization which is a common feature of the ferroelectric perovskites, there is an important hybridization between bismuth and oxygen states. The underlying static potential for the ferroelectric distortion and the primary source for ferroelectricity is investigated by a lattice-dynamics study using the Frozen Phonon approach.Comment: 17 pages, 7 figures. Phys. Rev. B, in pres

Psychological traits influence autonomic nervous system recovery following esophageal intubation in health and functional chest pain

Background: Esophageal intubation is a widely utilized technique for a diverse array of physiological studies, activating a complex physiological response mediated, in part, by the autonomic nervous system (ANS). In order to determine the optimal time period after intubation when physiological observations should be recorded, it is important to know the duration of, and factors that influence, this ANS response, in both health and disease. Methods: Fifty healthy subjects (27 males, median age 31.9 years, range 20-53 years) and 20 patients with Rome III defined functional chest pain (nine male, median age of 38.7 years, range 28-59 years) had personality traits and anxiety measured. Subjects had heart rate (HR), blood pressure (BP), sympathetic (cardiac sympathetic index, CSI), and parasympathetic nervous system (cardiac vagal tone, CVT) parameters measured at baseline and in response to per nasum intubation with an esophageal catheter. CSI/CVT recovery was measured following esophageal intubation. Key Results: In all subjects, esophageal intubation caused an elevation in HR, BP, CSI, and skin conductance response (SCR; all p < 0.0001) but concomitant CVT and cardiac sensitivity to the baroreflex (CSB) withdrawal (all p < 0.04). Multiple linear regression analysis demonstrated that longer CVT recovery times were independently associated with higher neuroticism (p < 0.001). Patients had prolonged CSI and CVT recovery times in comparison to healthy subjects (112.5 s vs 46.5 s, p = 0.0001 and 549 s vs 223.5 s, p = 0.0001, respectively). Conclusions & Inferences: Esophageal intubation activates a flight/flight ANS response. Future studies should allow for at least 10 min of recovery time. Consideration should be given to psychological traits and disease status as these can influence recovery. The psychological trait of neuroticism retards autonomic recovery following esophageal intubation in health and functional chest pain

Psychophysiological responses to visceral and somatic pain in functional chest pain identify clinically relevant pain clusters

Background: Despite chronic pain being a feature of functional chest pain (FCP) its experience is variable. The factors responsible for this variability remain unresolved. We aimed to address these knowledge gaps, hypothesizing that the psychophysiological profiles of FCP patients will be distinct from healthy subjects. Methods: 20 Rome III defined FCP patients (nine males, mean age 38.7 years, range 28-59 years) and 20 healthy age-, sex-, and ethnicity-matched controls (nine males, mean 38.2 years, range 24-49) had anxiety, depression, and personality traits measured. Subjects had sympathetic and parasympathetic nervous system parameters measured at baseline and continuously thereafter. Subjects received standardized somatic (nail bed pressure) and visceral (esophageal balloon distension) stimuli to pain tolerance. Venous blood was sampled for cortisol at baseline, post somatic pain and post visceral pain. Key Results: Patients had higher neuroticism, state and trait anxiety, and depression scores but lower extroversion scores vs controls (all p < 0.005). Patients tolerated less somatic (p < 0.0001) and visceral stimulus (p = 0.009) and had a higher cortisol at baseline, and following pain (all p < 0.001). At baseline, patients had a higher sympathetic tone (p = 0.04), whereas in response to pain they increased their parasympathetic tone (p ≤ 0.008). The amalgamating the data, we identified two psychophysiologically distinct 'pain clusters'. Patients were overrepresented in the cluster characterized by high neuroticism, trait anxiety, baseline cortisol, pain hypersensitivity, and parasympathetic response to pain (all p < 0.03). Conclusions & Inferences: In future, such delineations in FCP populations may facilitate individualization of treatment based on psychophysiological profiling