Probabilistic Analysis of Optimization Problems on Generalized Random Shortest Path Metrics

Simple heuristics often show a remarkable performance in practice for optimization problems. Worst-case analysis often falls short of explaining this performance. Because of this, "beyond worst-case analysis" of algorithms has recently gained a lot of attention, including probabilistic analysis of algorithms. The instances of many optimization problems are essentially a discrete metric space. Probabilistic analysis for such metric optimization problems has nevertheless mostly been conducted on instances drawn from Euclidean space, which provides a structure that is usually heavily exploited in the analysis. However, most instances from practice are not Euclidean. Little work has been done on metric instances drawn from other, more realistic, distributions. Some initial results have been obtained by Bringmann et al. (Algorithmica, 2013), who have used random shortest path metrics on complete graphs to analyze heuristics. The goal of this paper is to generalize these findings to non-complete graphs, especially Erd\H{o}s-R\'enyi random graphs. A random shortest path metric is constructed by drawing independent random edge weights for each edge in the graph and setting the distance between every pair of vertices to the length of a shortest path between them with respect to the drawn weights. For such instances, we prove that the greedy heuristic for the minimum distance maximum matching problem, the nearest neighbor and insertion heuristics for the traveling salesman problem, and a trivial heuristic for the $k$-median problem all achieve a constant expected approximation ratio. Additionally, we show a polynomial upper bound for the expected number of iterations of the 2-opt heuristic for the traveling salesman problem.Comment: An extended abstract appeared in the proceedings of WALCOM 201

Probabilistic Analysis of Facility Location on Random Shortest Path Metrics

The facility location problem is an NP-hard optimization problem. Therefore, approximation algorithms are often used to solve large instances. Such algorithms often perform much better than worst-case analysis suggests. Therefore, probabilistic analysis is a widely used tool to analyze such algorithms. Most research on probabilistic analysis of NP-hard optimization problems involving metric spaces, such as the facility location problem, has been focused on Euclidean instances, and also instances with independent (random) edge lengths, which are non-metric, have been researched. We would like to extend this knowledge to other, more general, metrics. We investigate the facility location problem using random shortest path metrics. We analyze some probabilistic properties for a simple greedy heuristic which gives a solution to the facility location problem: opening the $\kappa$ cheapest facilities (with $\kappa$ only depending on the facility opening costs). If the facility opening costs are such that $\kappa$ is not too large, then we show that this heuristic is asymptotically optimal. On the other hand, for large values of $\kappa$, the analysis becomes more difficult, and we provide a closed-form expression as upper bound for the expected approximation ratio. In the special case where all facility opening costs are equal this closed-form expression reduces to $O(\sqrt[4]{\ln(n)})$ or $O(1)$ or even $1+o(1)$ if the opening costs are sufficiently small.Comment: A preliminary version accepted to CiE 201

Commentary on strategies for switching antipsychotics

Both the new generation of antipsychotics and the more traditional antipsychotic drugs produce an important and meaningful improvement in patients with schizophrenia, but most patients are neither cured nor free of symptoms. As a consequence, it is common to switch from one drug to another in the hope of obtaining a better response. All antipsychotic drugs produce some side effects, so switching can also be a tolerance issue. There are reports in the literature on the tactics of switching: abrupt discontinuation, cross tapering, starting a patient on a new drug while continuing with the old drug until the new drug has reached a steady state, or some variation on these tactics. In this issue, Ganguli et al. have carried out a randomized switching study, the data from which indicates the tactics that might be optimal. We put this paper into context, provide a critique and describe indications for switching

Npas4 is activated by melatonin, and drives the clock gene Cry1 in the ovine pars tuberalis

Seasonal mammalsintegrate changes in the duration of nocturnal melatonin secretion to drive annual physiologic cycles. Melatonin receptors within the proximal pituitary region, the pars tuberalis (PT), are essential in regulating seasonal neuroendocrine responses. In the ovine PT, melatonin is known to influence acute changes in transcriptional dynamics coupled to the onset (dusk) and offset (dawn) of melatonin secretion, leading to a potential interval-timing mechanism capable of decoding changes in day length (photoperiod). Melatonin offset at dawn is linked to cAMP accumulation, which directly induces transcription of the clock gene Per1. The rise of melatonin at dusk induces a separate and distinct cohort, including the clock-regulated genes Cry1 and Nampt, but little is known of the upstream mechanisms involved. Here, we used next-generation sequencing of the ovine PT transcriptome at melatonin onset and identified Npas4 as a rapidly induced basic helix-loop-helix Per-Arnt-Sim domain transcription factor. In vivo we show nuclear localization of NPAS4 protein in presumptive melatonin target cells of the PT (α-glycoprotein hormone-expressing cells), whereas in situ hybridization studies identified acute and transient expression in the PT of Npas4 in response to melatonin. In vitro, NPAS4 forms functional dimers with basic helix loop helix-PAS domain cofactors aryl hydrocarbon receptor nuclear translocator (ARNT), ARNT2, and ARNTL, transactivating both Cry1 and Nampt ovine promoter reporters. Using a combination of 5'-deletions and site-directed mutagenesis, we show NPAS4-ARNT transactivation to be codependent upon two conserved central midline elements within the Cry1 promoter. Our data thus reveal NPAS4 as a candidate immediate early-response gene in the ovine PT, driving molecular responses to melatonin

Surveillance of antimicrobial resistance at a tertiary hospital in Tanzania

BACKGROUND: Antimicrobial resistance is particularly harmful to infectious disease management in low-income countries since expensive second-line drugs are not readily available. The objective of this study was to implement and evaluate a computerized system for surveillance of antimicrobial resistance at a tertiary hospital in Tanzania. METHODS: A computerized surveillance system for antimicrobial susceptibility (WHONET) was implemented at the national referral hospital in Tanzania in 1998. The antimicrobial susceptibilities of all clinical bacterial isolates received during an 18 months' period were recorded and analyzed. RESULTS: The surveillance system was successfully implemented at the hospital. This activity increased the focus on antimicrobial resistance issues and on laboratory quality assurance issues. The study identified specific nosocomial problems in the hospital and led to the initiation of other prospective studies on prevalence and antimicrobial susceptibility of bacterial infections. Furthermore, the study provided useful data on antimicrobial patterns in bacterial isolates from the hospital. Gram-negative bacteria displayed high rates of resistance to common inexpensive antibiotics such as ampicillin, tetracycline and trimethoprim-sulfamethoxazole, leaving fluoroquinolones as the only reliable oral drugs against common Gram-negative bacilli. Gentamicin and third generation cephalosporins remain useful for parenteral therapy. CONCLUSION: The surveillance system is a low-cost tool to generate valuable information on antimicrobial resistance, which can be used to prepare locally applicable recommendations on antimicrobial use. The system pinpoints relevant nosocomial problems and can be used to efficiently plan further research. The surveillance system also functions as a quality assurance tool, bringing attention to methodological issues in identification and susceptibility testing

A Tonnetz Model for pentachords

This article deals with the construction of surfaces that are suitable for representing pentachords or 5-pitch segments that are in the same $T/I$ class. It is a generalization of the well known \"Ottingen-Riemann torus for triads of neo-Riemannian theories. Two pentachords are near if they differ by a particular set of contextual inversions and the whole contextual group of inversions produces a Tiling (Tessellation) by pentagons on the surfaces. A description of the surfaces as coverings of a particular Tiling is given in the twelve-tone enharmonic scale case.Comment: 27 pages, 12 figure

Minsky machines and algorithmic problems

This is a survey of using Minsky machines to study algorithmic problems in semigroups, groups and other algebraic systems.Comment: 19 page

Pulmonary stretch receptor activity during partial liquid ventilation in cats with healthy lungs

Aim: To study whether pulmonary stretch receptor (PSR) activity in mechanically ventilated young cats with healthy lungs during partial liquid ventilation (PLV) is different from that during gas ventilation (GV). Methods: In 10 young cats (4.4 +/- 0.4 months, 2.3 +/- 0.3 kg; mean B SD), PSR instantaneous impulse frequency (PSR f(imp)) was recorded from single fibres in the vagal nerve during GV and PLV with perfluorocarbon (30 ml/kg) at increasing positive inspiratory pressures (PIP; 1.2, 1.8, 2.2 and 2.7 kPa), and at a positive end-expiratory pressure of 0.5 kPa. Results: All PSRs studied during GV maintained their phasic character with increased impulse frequency during inspiration during PLV. Peak PSR fimp was lower at PIP 1.2 kPa (p < 0.05) and at PIP 2.7 kPa (p = 0.10) during PLV than during GV, giving a lower number of PSR impulses at these two settings during PLV (p < 0.05). Conclusion: The phasic character of PSR activity is similar during GV and PLV. PSR activity is not higher during PLV than during GV in cats with healthy lungs, indicating no extensive stretching of the lung during PLV. Copyright (C) 2004 S. Karger AG, Basel

Allocating the Burdens of Climate Action: Consumption-Based Carbon Accounting and the Polluter-Pays Principle

Action must be taken to combat climate change. Yet, how the costs of climate action should be allocated among states remains a question. One popular answer—the polluter-pays principle (PPP)—stipulates that those responsible for causing the problem should pay to address it. While intuitively plausible, the PPP has been subjected to withering criticism in recent years. It is timely, following the Paris Agreement, to develop a new version: one that does not focus on historical production-based emissions but rather allocates climate burdens in proportion to each state’s annual consumption-based emissions. This change in carbon accounting results in a fairer and more environmentally effective principle for distributing climate duties

Heterozygote Advantage for Fecundity

Heterozygote advantage, or overdominance, remains a popular and persuasive explanation for the maintenance of genetic variation in natural populations in the face of selection. However, despite being first proposed more than 80 years ago, there remain few examples that fit the criteria for heterozygote advantage, all of which are associated with disease resistance and are maintained only in the presence of disease or other gene-by-environment interaction. Here we report five new examples of heterozygote advantage, based around polymorphisms in the BMP15 and GDF9 genes that affect female fecundity in domesticated sheep and are not reliant on disease for their maintenance. Five separate mutations in these members of the transforming growth factor β (TGFβ) superfamily give phenotypes with fitness differentials characteristic of heterozygous advantage. In each case, one copy of the mutant allele increases ovulation rate, and ultimately litter size per ewe lambing, relative to the wildtype. However, homozygous ewes inheriting mutant alleles from both parents have impaired oocyte development and maturation, which results in small undeveloped ovaries and infertility. Using data collected over many years on ovulation rates, litter size, and lambing rates, we have calculated the equilibrium solution for each of these polymorphisms using standard population genetic theory. The predicted equilibrium frequencies obtained for these mutant alleles range from 0.11 to 0.23, which are amongst the highest yet reported for a polymorphism maintained by heterozygote advantage. These are amongst the most frequent and compelling examples of heterozygote advantage yet described and the first documented examples of heterozygote advantage that are not reliant on a disease interaction for their maintenance