Unwinding of a cholesteric liquid crystal and bidirectional surface anchoring

We examine the influence of bidirectional anchoring on the unwinding of a planar cholesteric liquid crystal induced by the application of a magnetic field. We consider a liquid crystal layer confined between two plates with the helical axis perpendicular to the substrates. We fixed the director twist on one boundary and allow for bidirectional anchoring on the other by introducing a high-order surface potential. By minimizing the total free energy for the system, we investigate the untwisting of the cholesteric helix as the liquid crystal attempts to align with the magnetic field. The transitions between metastable states occur as a series of pitchjumps as the helix expels quarter or half-turn twists, depending on the relative sizes of the strength of the surface potential and the bidirectional anchoring. We show that secondary easy axis directions can play a significant role in the unwinding of the cholesteric in its transition towards a nematic, especially when the surface anchoring strength is large

How to Specify It!: A Guide to Writing Properties of Pure Functions

Property-based testing tools test software against a\ua0specification, rather than a set of examples. This tutorial paper presents five generic approaches to writing such specifications (for purely functional code). We discuss the costs, benefits, and bug-finding power of each approach, with reference to a simple example with eight buggy variants. The lessons learned should help the reader to develop effective property-based tests in the future

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Correlation between nucleotide composition and folding energy of coding sequences with special attention to wobble bases

Background: The secondary structure and complexity of mRNA influences its accessibility to regulatory molecules (proteins, micro-RNAs), its stability and its level of expression. The mobile elements of the RNA sequence, the wobble bases, are expected to regulate the formation of structures encompassing coding sequences. Results: The sequence/folding energy (FE) relationship was studied by statistical, bioinformatic methods in 90 CDS containing 26,370 codons. I found that the FE (dG) associated with coding sequences is significant and negative (407 kcal/1000 bases, mean +/- S.E.M.) indicating that these sequences are able to form structures. However, the FE has only a small free component, less than 10% of the total. The contribution of the 1st and 3rd codon bases to the FE is larger than the contribution of the 2nd (central) bases. It is possible to achieve a ~ 4-fold change in FE by altering the wobble bases in synonymous codons. The sequence/FE relationship can be described with a simple algorithm, and the total FE can be predicted solely from the sequence composition of the nucleic acid. The contributions of different synonymous codons to the FE are additive and one codon cannot replace another. The accumulated contributions of synonymous codons of an amino acid to the total folding energy of an mRNA is strongly correlated to the relative amount of that amino acid in the translated protein. Conclusion: Synonymous codons are not interchangable with regard to their role in determining the mRNA FE and the relative amounts of amino acids in the translated protein, even if they are indistinguishable in respect of amino acid coding.Comment: 14 pages including 6 figures and 1 tabl

A Cross-Sectional Study of People with Epilepsy and Neurocysticercosis in Tanzania: Clinical Characteristics and Diagnostic Approaches.

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa

Phosphorylation of the Leukemic Oncoprotein EVI1 on Serine 196 Modulates DNA Binding, Transcriptional Repression and Transforming Ability

The EVI1 (ecotropic viral integration site 1) gene at 3q26 codes for a transcriptional regulator with an essential role in haematopoiesis. Overexpression of EVI1 in acute myeloid leukaemia (AML) is frequently associated with 3q26 rearrangements and confers extremely poor prognosis. EVI1 mediates transcriptional regulation, signalling, and epigenetic modifications by interacting with DNA, proteins and protein complexes. To explore to what extent protein phosphorylation impacts on EVI1 functions, we analysed endogenous EVI1 protein from a high EVI1 expressing Fanconi anaemia (FA) derived AML cell line. Mass spectrometric analysis of immunoprecipitated EVI1 revealed phosphorylation at serine 196 (S196) in the sixth zinc finger of the N-terminal zinc finger domain. Mutated EVI1 with an aspartate substitution at serine 196 (S196D), which mimics serine phosphorylation of this site, exhibited reduced DNA-binding and transcriptional repression from a gene promotor selectively targeted by the N-terminal zinc finger domain. Forced expression of the S196D mutant significantly reduced EVI1 mediated transformation of Rat1 fibroblasts. While EVI1-mediated serial replating of murine haematopoietic progenitors was maintained by EVI1-S196D, this was associated with significantly higher Evi1-trancript levels compared with WT-EVI1 or EVI1-S196A, mimicking S196 non-phosphorylated EVI1. These data suggest that EVI1 function is modulated by phosphorylation of the first zinc finger domain

Validity, reliability and stability of the portable Cortex Metamax 3B gas analysis system

This study investigated the performance of the portable Cortex Metamax 3B (MM3B) automated gas analysis system during both simulated and human exercise using adolescents. Repeated measures using a Gas Exchange System Validator (GESV) across a range of simulated metabolic rates, showed the MM3B to be adequately reliable (both percentage errors, and percentage technical error of measurements <2%) for measuring expired ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2). Over a 3 h period, the MM3B was shown to be acceptably stable in measuring gas fractions, as well as VE, VO2, and VCO2 generated by the GESV, especially at moderate and high metabolic rates (drifts <2% and of minor physiological significance). Using eight healthy adolescents during rest, moderate, and vigorous cycle ergometry, the validity of the MM3B was tested against the primary criterion Douglas bag method (DBM) and a secondary criterion machine known to be accurate, the Jaeger Oxycon Pro system. No significant errors in VE were noted, yet the MM3B significantly overestimated both VO2 and VCO2 by approximately 10–17% at moderate and vigorous exercise as compared to the DBM and at all exercise levels compared to the Oxycon Pro. No significant differences were seen in any metabolic variable between the two criterion systems (DBM and Oxycon Pro). It is concluded the MM3B produces acceptably stable and reliable results, but is not adequately valid during moderate and vigorous exercise without some further correction of VO2 and VCO2

Pre-segmented 2-Step IMRT with subsequent direct machine parameter optimisation – a planning study

<p>Abstract</p> <p>Background</p> <p>Modern intensity modulated radiotherapy (IMRT) mostly uses iterative optimisation methods. The integration of machine parameters into the optimisation process of step and shoot leaf positions has been shown to be successful. For IMRT segmentation algorithms based on the analysis of the geometrical structure of the planning target volumes (PTV) and the organs at risk (OAR), the potential of such procedures has not yet been fully explored. In this work, 2-Step IMRT was combined with subsequent direct machine parameter optimisation (DMPO-Raysearch Laboratories, Sweden) to investigate this potential.</p> <p>Methods</p> <p>In a planning study DMPO on a commercial planning system was compared with manual primary 2-Step IMRT segment generation followed by DMPO optimisation. 15 clinical cases and the ESTRO Quasimodo phantom were employed. Both the same number of optimisation steps and the same set of objective values were used. The plans were compared with a clinical DMPO reference plan and a traditional IMRT plan based on fluence optimisation and consequent segmentation. The composite objective value (the weighted sum of quadratic deviations of the objective values and the related points in the dose volume histogram) was used as a measure for the plan quality. Additionally, a more extended set of parameters was used for the breast cases to compare the plans.</p> <p>Results</p> <p>The plans with segments pre-defined with 2-Step IMRT were slightly superior to DMPO alone in the majority of cases. The composite objective value tended to be even lower for a smaller number of segments. The total number of monitor units was slightly higher than for the DMPO-plans. Traditional IMRT fluence optimisation with subsequent segmentation could not compete.</p> <p>Conclusion</p> <p>2-Step IMRT segmentation is suitable as starting point for further DMPO optimisation and, in general, results in less complex plans which are equal or superior to plans generated by DMPO alone.</p

The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products