On the String Consensus Problem and the Manhattan Sequence Consensus Problem

In the Manhattan Sequence Consensus problem (MSC problem) we are given $k$ integer sequences, each of length $l$, and we are to find an integer sequence $x$ of length $l$ (called a consensus sequence), such that the maximum Manhattan distance of $x$ from each of the input sequences is minimized. For binary sequences Manhattan distance coincides with Hamming distance, hence in this case the string consensus problem (also called string center problem or closest string problem) is a special case of MSC. Our main result is a practically efficient $O(l)$-time algorithm solving MSC for $k\le 5$ sequences. Practicality of our algorithms has been verified experimentally. It improves upon the quadratic algorithm by Amir et al.\ (SPIRE 2012) for string consensus problem for $k=5$ binary strings. Similarly as in Amir's algorithm we use a column-based framework. We replace the implied general integer linear programming by its easy special cases, due to combinatorial properties of the MSC for $k\le 5$. We also show that for a general parameter $k$ any instance can be reduced in linear time to a kernel of size $k!$, so the problem is fixed-parameter tractable. Nevertheless, for $k\ge 4$ this is still too large for any naive solution to be feasible in practice.Comment: accepted to SPIRE 201

Dimensionless cosmology

Although it is well known that any consideration of the variations of fundamental constants should be restricted to their dimensionless combinations, the literature on variations of the gravitational constant $G$ is entirely dimensionful. To illustrate applications of this to cosmology, we explicitly give a dimensionless version of the parameters of the standard cosmological model, and describe the physics of Big Bang Neucleosynthesis and recombination in a dimensionless manner. The issue that appears to have been missed in many studies is that in cosmology the strength of gravity is bound up in the cosmological equations, and the epoch at which we live is a crucial part of the model. We argue that it is useful to consider the hypothetical situation of communicating with another civilization (with entirely different units), comparing only dimensionless constants, in order to decide if we live in a Universe governed by precisely the same physical laws. In this thought experiment, we would also have to compare epochs, which can be defined by giving the value of any {\it one} of the evolving cosmological parameters. By setting things up carefully in this way one can avoid inconsistent results when considering variable constants, caused by effectively fixing more than one parameter today. We show examples of this effect by considering microwave background anisotropies, being careful to maintain dimensionlessness throughout. We present Fisher matrix calculations to estimate how well the fine structure constants for electromagnetism and gravity can be determined with future microwave background experiments. We highlight how one can be misled by simply adding $G$ to the usual cosmological parameter set

Antibacterial Resistance Leadership Group 2.0: Back to Business

In December 2019, the Antibacterial Resistance Leadership Group (ARLG) was awarded funding for another 7-year cycle to support a clinical research network on antibacterial resistance. ARLG 2.0 has 3 overarching research priorities: infections caused by antibiotic-resistant (AR) gram-negative bacteria, infections caused by AR gram-positive bacteria, and diagnostic tests to optimize use of antibiotics. To support the next generation of AR researchers, the ARLG offers 3 mentoring opportunities: the ARLG Fellowship, Early Stage Investigator seed grants, and the Trialists in Training Program. The purpose of this article is to update the scientific community on the progress made in the original funding period and to encourage submission of clinical research that addresses 1 or more of the research priority areas of ARLG 2.0

Treatment of hepatitis C monoinfection in adults - Dutch national guidelines

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

A fully validated microbiological assay for daptomycin injection and comparison to HPLC method

abstract Daptomycin (DPT) was the first lipopeptide antibiotic available for commercialization. It is active against gram-positive bacteria, including resistant strains. This work aimed to develop and validate a turbidimetric microbiologic assay to determine daptomycin in an injectable form. A 3x3 design was employed, at concentrations of 1, 2 and 4.0 µg/mL. The microorganism test used was Staphylococcus aureus ATCC 6538p, and Antibiotic Medium 3 was used as the culture medium. Method validation demonstrated that the bioassay was linear (r=0.9995), precise (RSD=2.58%), accurate (recovery 100.48± 2.11%), and robust. Degradation kinetics was also performed in an alkaline medium, indicating that daptomycin degradation follows first order kinetics under these conditions. The analyses of degraded solutions showed that daptomycin degradation products do not possess bactericidal activity. The bioassay was compared to HPLC method that was previously developed and no significant difference was found between them (p>0.05). The method proved to be appropriate for daptomycin injection quality control

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

CdTe ambulatory ventricular function monitor

A prototype device consisting of two arrays of CdTe detectors, ECG amplifiers and gate, microprocessor, and tape recorder was devised to record simultaneous ECG and radionuclide blood pool data from the left ventricle for extended periods during normal activity. The device is intended to record information concerning both normal and abnormal physiology of the heart and to permit the evaluation of new pharmaceuticals under everyday conditions. Preliminary results indicate that the device is capable of recording and reading out data from both phantoms and patients