Refighting Pickett’s Charge: mathematical modeling of the Civil War battlefield

Objective. We model Pickett’s Charge at the Battle of Gettysburg to see whether the Confederates could have achieved victory by committing more infantry, executing a better barrage, or facing a weaker defense. Methods. Our mathematical modeling is based on Lanchester equations, calibrated using historical army strengths. We weight the Union artillery and infantry two different ways using two sources of data, and so have four versions of the model. Results. The models estimate that a successful Confederate charge would have required at least 1 to 3 additional brigades. An improved artillery barrage would have reduced these needs by about 1 brigade. A weaker Union defense could have allowed the charge to succeed as executed. Conclusions. The Confederates plausibly had enough troops to take the Union position and alter the battle’s outcome, but likely too few to further exploit such a success

Does the availability of snack foods in supermarkets vary internationally?

BackgroundCross-country differences in dietary behaviours and obesity rates have been previously reported. Consumption of energy-dense snack foods and soft drinks are implicated as contributing to weight gain, however little is known about how the availability of these items within supermarkets varies internationally. This study assessed variations in the display of snack foods and soft drinks within a sample of supermarkets across eight countries.MethodsWithin-store audits were used to evaluate and compare the availability of potato chips (crisps), chocolate, confectionery and soft drinks. Displays measured included shelf length and the proportion of checkouts and end-of-aisle displays containing these products. Audits were conducted in a convenience sample of 170 supermarkets across eight developed nations (Australia, Canada, Denmark, Netherlands, New Zealand, Sweden, United Kingdom (UK), and United States of America (US)).ResultsThe mean total aisle length of snack foods (adjusted for store size) was greatest in supermarkets from the UK (56.4 m) and lowest in New Zealand (21.7 m). When assessed by individual item, the greatest aisle length devoted to chips, chocolate and confectionery was found in UK supermarkets while the greatest aisle length dedicated to soft drinks was in Australian supermarkets. Only stores from the Netherlands (41%) had less than 70% of checkouts featuring displays of snack foods or soft drinks.ConclusionWhilst between-country variations were observed, overall results indicate high levels of snack food and soft drinks displays within supermarkets across the eight countries. Exposure to snack foods is largely unavoidable within supermarkets, increasing the likelihood of purchases and particularly those made impulsively.<br /

SpBase: the sea urchin genome database and web site

SpBase is a system of databases focused on the genomic information from sea urchins and related echinoderms. It is exposed to the public through a web site served with open source software (http://spbase.org/). The enterprise was undertaken to provide an easily used collection of information to directly support experimental work on these useful research models in cell and developmental biology. The information served from the databases emerges from the draft genomic sequence of the purple sea urchin, Strongylocentrotus purpuratus and includes sequence data and genomic resource descriptions for other members of the echinoderm clade which in total span 540 million years of evolutionary time. This version of the system contains two assemblies of the purple sea urchin genome, associated expressed sequences, gene annotations and accessory resources. Search mechanisms for the sequences and the gene annotations are provided. Because the system is maintained along with the Sea Urchin Genome resource, a database of sequenced clones is also provided

Updating our understanding of health-related quality of life issues in children with cancer: a systematic review of patient-reported outcome measures and qualitative studies

publishedVersionPaid open acces

MTL-CEBPA, a small activating RNA therapeutic upregulating C/EBP-α, in patients with advanced liver cancer: a first-in-human, multicenter, open-label, phase I trial

Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug which up-regulates C/EBP-α. Experimental Design: We conducted a phase I, open label, dose escalation trial of MTL-CEBPA in adults with advanced HCC with cirrhosis, or resulting from non-alcoholic steatohepatitis (NASH) or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose escalation phase (3+3 design). Results: 38 participants have been treated across 6 dose levels (28-160 mg/m2) and 3 dosing schedules. 34 patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose and no maximum dose was reached across the 3 schedules evaluated. Grade 3 treatment related adverse events occurred in 9 (24%) patients. In 24 HCC patients evaluable for efficacy, an objective tumour response was achieved in 1 patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKI); 3 patients had a complete response with one further PR and two with SD. Conclusions: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging Phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC

Characteristic Male Urine Microbiomes Associate with Asymptomatic Sexually Transmitted Infection

Article discussing research on characteristic male urine microbiomes associated with asymptomatic sexually transmitted infection

Phosphate transporters in marine phytoplankton and their viruses: Cross-domain commonalities in viral-host gene exchanges

Phosphate (PO 4) is an important limiting nutrient in marine environments. Marine cyanobacteria scavenge PO 4 using the high-affinity periplasmic phosphate binding protein PstS. The pstS gene has recently been identified in genomes of cyanobacterial viruses as well. Here, we analyse genes encoding transporters in genomes from viruses that infect eukaryotic phytoplankton. We identified inorganic PO 4 transporter-encoding genes from the PHO4 superfamily in several virus genomes, along with other transporter-encoding genes. Homologues of the viral pho4 genes were also identified in genome sequences from the genera that these viruses infect. Genome sequences were available from host genera of all the phytoplankton viruses analysed except the host genus Bathycoccus. Pho4 was recovered from Bathycoccus by sequencing a targeted metagenome from an uncultured Atlantic Ocean population. Phylogenetic reconstruction showed that pho4 genes from pelagophytes, haptophytes and infecting viruses were more closely related to homologues in prasinophytes than to those in what, at the species level, are considered to be closer relatives (e.g. diatoms). We also identified PHO4 superfamily members in ocean metagenomes, including new metagenomes from the Pacific Ocean. The environmental sequences grouped with pelagophytes, haptophytes, prasinophytes and viruses as well as bacteria. The analyses suggest that multiple independent pho4 gene transfer events have occurred between marine viruses and both eukaryotic and bacterial hosts. Additionally, pho4 genes were identified in available genomes from viruses that infect marine eukaryotes but not those that infect terrestrial hosts. Commonalities in marine host-virus gene exchanges indicate that manipulation of host-PO 4 uptake is an important adaptation for viral proliferation in marine systems. Our findings suggest that PO 4-availability may not serve as a simple bottom-up control of marine phytoplankton. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd

Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays

<p>Abstract</p> <p>Background</p> <p>Syphilis spirochete <it>Treponema pallidum </it>ssp. <it>pallidum </it>remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently.</p> <p>Results</p> <p>The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the <it>T. pallidum </it>chromosome.</p> <p>Conclusion</p> <p>The observed genetic changes do not have influence on the ability of <it>Treponema pallidum </it>to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.</p

Compositional Genome Contexts Affect Gene Expression Control in Sea Urchin Embryo

Gene expression is widely perceived as exclusively controlled by the information contained in cis-regulatory regions. These are built in a modular way, each module being a cluster of binding sites for the transcription factors that control the level, the location and the time at which gene transcription takes place. On the other hand, results from our laboratory have shown that gene expression is affected by the compositional properties (GC levels) of the isochores in which genes are embedded, i.e. the genome context. To clarify how compositional genomic properties affect the way cis-regulatory information is utilized, we have changed the genome context of a GFP-reporter gene containing the complete cis-regulatory region of the gene spdeadringer (spdri), expressed during sea urchin embryogenesis. We have observed that GC levels higher or lower than those found in the natural genome context can alter the reporter expression pattern. We explain this as the result of an interference with the functionality of specific modules in the gene's cis-regulatory region. From these observations we derive the notion that the compositional properties of the genome context can affect cis-regulatory control of gene expression. Therefore although the way a gene works depends on the information contained in its cis-regulatory region, availability of such information depends on the compositional properties of the genomic context