A modified electromagnetism-like algorithm based on a pattern search method

The Electromagnetism-like (EM) algorithm, developed by Birbil and Fang [2] is a population-based stochastic global optimization algorithm that uses an attraction-repulsion mechanism to move sample points towards optimality. A typical EM algorithm for solving continuous bound constrained optimization problems performs a local search in order to gather information for a point, in the population. Here, we propose a new local search procedure based on the original pattern search method of Hooke and Jeeves, which is simple to implement and does not require any derivative information. The proposed method is applied to different test problems from the literature and compared with the original EM algorithm.(undefined

A model for measuring the health burden of classic congenital adrenal hyperplasia in adults

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Aim: Patients with classic Congenital Adrenal Hyperplasia (CAH) have poor health outcomes. In the absence of a comprehensive observational study, this manuscript provides a model to estimate the lifetime disease burden of adults with classic CAH. Methods: The model, built in Excel, comprises sub-domains addressing the health consequences of CAH, and synthesises evidence from clinical and epidemiological studies on health outcomes. Results: The model estimates that adults with classic CAH will implement “sick day rules” (doubling or tripling glucocorticoid and/or use of parenteral therapy) 171 times over their lifetime, and attend hospital for adrenal crisis on 11 occasions. In a population of 1,000, over 200 will die of a condition complicated by adrenal crisis resulting, on average, in a loss of 7 years of life. CAH patients may also suffer from excess CVD events. Treatment with glucocorticoids almost doubles the risk of bone fractures in CAH patients compared to the general population, leading on average to an additional 0.8 fractures per CAH patient over their lifetime. Conclusions: The disease burden model highlights gaps in evidence, particularly regarding intensity of care and adrenal crisis, and the relationship between control of CAH and risks of CVD, osteoporosis, diabetes and infertility. The model can be used for research on the impact of new clinical pathways and therapeutic interventions in terms of clinical events and cost.Funded by: European Commission under the Framework 7 programme. Grant Number: HEALTH-F5-2011-281654Diurnal Limited (UK

Tertiary hypothyroidism in a dog

<p/> <p>A nine-year-old male entire Labrador was diagnosed with pituitary dependent hyperadrenocorticism. Following seven months of successful mitotane therapy, the dog presented with marked weight gain, seborrhoea and alopecia. Routine clinicopathological analyses revealed marked hypercholesterolaemia. Serum total and free thyroxine (T4) concentrations were below their respective reference ranges. Serum thyroid stimulating hormone (cTSH) concentration was within reference range. TSH and thyrotropin releasing hormone (TRH) response tests revealed adequate stimulation of total T4 in both, and cTSH in the latter test. Magnetic resonance imaging revealed a mass arising from the pituitary fossa, with suprasellar extension. A diagnosis of tertiary hypothyroidism was made. Following four weeks of levothyroxine therapy, circulating cholesterol concentration had declined, weight loss had ensued and dermatological abnormalities had improved. Euthanasia was performed four months later due to the development of neurological signs. A highly infiltrative pituitary adenoma, with effacement of the overlying hypothalamus was identified on post mortem examination. Tertiary hypothyroidism has not been previously reported in dogs.</p

Prevention of poxvirus infection by tetrapyrroles

BACKGROUND: Prevention of poxvirus infection is a topic of great current interest. We report inhibition of vaccinia virus in cell culture by porphyrins and phthalocyanines. Most previous work on the inhibition of viruses with tetrapyrroles has involved photodynamic mechanisms. The current study, however, investigates light-independent inhibition activity. METHODS: The Western Reserve (WR) and International Health Department-J (IHD-J) strains of vaccinia virus were used. Virucidal and antiviral activities as well as the cytotoxicity of test compounds were determined. RESULTS: Examples of active compounds include zinc protoporphyrin, copper hematoporphyrin, meso(2,6-dihydroxyphenyl)porphyrin, the sulfonated tetra-1-naphthyl and tetra-1-anthracenylporphyrins, selected sulfonated derivatives of halogenated tetraphenyl porphyrins and the copper chelate of tetrasulfonated phthalocyanine. EC(50 )values for the most active compounds are as low as 0.05 µg/mL (40 nM). One of the most active compounds was the neutral meso(2,6-dihydroxyphenyl)porphyrin, indicating that the compounds do not have to be negatively charged to be active. CONCLUSIONS: Porphyrins and phthalocyanines have been found to be potent inhibitors of infection by vaccinia virus in cell culture. These tetrapyrroles were found to be active against two different virus strains, and against both enveloped and non-enveloped forms of the virus, indicating that these compounds may be broadly effective in their ability to inhibit poxvirus infection

Synthesis, Structure and Stereodynamics of Atropisomeric <em>N</em>‑Chloroamides

Atropisomeric N-chloroamides were efficiently accessed by electrophilic halogenation of ortho-substituted secondary anilides. The stereodynamics of atropisomerism in these novel scaffolds was interrogated by detailed experimental and computational studies, revealing that racemization is correlated with amide isomerization. The stereoelectronic nature of the amide was shown to significantly influence racemization rates, with potentially important implications for other C-N atropisomeric scaffolds

Phase II study of the oxygen saturation curve left shifting agent BW12C in combination with the hypoxia activated drug mitomycin C in advanced colorectal cancer

BW12C (5-[2-formyl-3-hydroxypenoxyl] pentanoic acid) stabilizes oxyhaemoglobin, causing a reversible left-shift of the oxygen saturation curve (OSC) and tissue hypoxia. The activity of mitomycin C (MMC) is enhanced by hypoxia. In this phase II study, 17 patients with metastatic colorectal cancer resistant to 5-fluorouracil (5-FU) received BW12C and MMC. BW12C was given as a bolus loading dose of 45 mg kg−1over 1 h, followed by a maintenance infusion of 4 mg kg−1h−1for 5 h. MMC 6 mg m−2was administered over 15 min immediately after the BW12C bolus. The 15 evaluable patients had progressive disease after a median of 2 (range 1–4) cycles of chemotherapy. Haemoglobin electrophoresis 3 and 5 h after the BW12C bolus dose showed a fast moving band consistent with the BW12C-oxyhaemoglobin complex, accounting for approximately 50% of total haemoglobin. The predominant toxicities – nausea/vomiting and vein pain – were mild and did not exceed CTC grade 2. Liver31P magnetic resonance spectroscopy of patients with hepatic metastases showed no changes consistent with tissue hypoxia. The principle of combining a hypoxically activated drug with an agent that increases tissue hypoxia is clinically feasible, producing an effect equivalent to reducing tumour oxygen delivery by at least 50%. However, BW12C in combination with MMC for 5-FU-resistant colorectal cancer is not an effective regimen. This could be related to drug resistance rather than a failure to enhance cytotoxicity. © 2000 Cancer Research Campaig

Imaging high-dimensional spatial entanglement with a camera

The light produced by parametric down-conversion shows strong spatial entanglement that leads to violations of EPR criteria for separability. Historically, such studies have been performed by scanning a single-element, single-photon detector across a detection plane. Here we show that modern electron-multiplying charge-coupled device cameras can measure correlations in both position and momentum across a multi-pixel field of view. This capability allows us to observe entanglement of around 2,500 spatial states and demonstrate Einstein-Podolsky-Rosen type correlations by more than two orders of magnitude. More generally, our work shows that cameras can lead to important new capabilities in quantum optics and quantum information science.Comment: 5 pages, 4 figure

Structure and function of a spectrin-like regulator of bacterial cytokinesis

© 2014 Macmillan Publishers Limited. All rights reserved. Bacterial cell division is facilitated by a molecular machine - the divisome - that assembles at mid-cell in dividing cells. The formation of the cytokinetic Z-ring by the tubulin homologue FtsZ is regulated by several factors, including the divisome component EzrA. Here we describe the structure of the 60-kDa cytoplasmic domain of EzrA, which comprises five linear repeats of an unusual triple helical bundle. The EzrA structure is bent into a semicircle, providing the protein with the potential to interact at both N- and C-termini with adjacent membrane-bound divisome components. We also identify at least two binding sites for FtsZ on EzrA and map regions of EzrA that are responsible for regulating FtsZ assembly. The individual repeats, and their linear organization, are homologous to the spectrin proteins that connect actin filaments to the membrane in eukaryotes, and we thus propose that EzrA is the founding member of the bacterial spectrin family

An acoustic emission landslide early warning system for communities in low-income and middle-income countries

This is an Open Access Article. It is published by Springer under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/Early warning systems for slope instability are needed to alert users of accelerating slope deformation behaviour, enable evacuation of vulnerable people, and conduct timely repair and maintenance of critical infrastructure. Communities exposed to landslide risk in low- and middle-income countries seldom currently instrument and monitor slopes to provide a warning of instability because existing techniques are complex and prohibitively expensive. Research and field trials have demonstrated conclusively that acoustic emission (AE) monitoring can be an effective approach to detect accelerating slope movements and to subsequently communicate warnings to users. The objective of this study was to develop and assess a simple, robust, low-cost AE monitoring system to warn of incipient landslides, which can be widely deployed and operated by communities globally to help protect vulnerable people. This paper describes a novel AE measurement sensor that has been designed and developed with the cost constrained to a few hundred dollars (US). Results are presented from physical model experiments that demonstrate performance of the AE system in measuring accelerating deformation behaviour, with quantifiable relationships between AE and displacement rates. Exceedance of a pre-determined trigger level of AE can be used to communicate an alarm to users in order to alert them of a slope failure. Use of this EWS approach by communities worldwide would reduce the number of fatalities caused by landslides

Single-valued harmonic polylogarithms and the multi-Regge limit

We argue that the natural functions for describing the multi-Regge limit of six-gluon scattering in planar N=4 super Yang-Mills theory are the single-valued harmonic polylogarithmic functions introduced by Brown. These functions depend on a single complex variable and its conjugate, (w,w*). Using these functions, and formulas due to Fadin, Lipatov and Prygarin, we determine the six-gluon MHV remainder function in the leading-logarithmic approximation (LLA) in this limit through ten loops, and the next-to-LLA (NLLA) terms through nine loops. In separate work, we have determined the symbol of the four-loop remainder function for general kinematics, up to 113 constants. Taking its multi-Regge limit and matching to our four-loop LLA and NLLA results, we fix all but one of the constants that survive in this limit. The multi-Regge limit factorizes in the variables (\nu,n) which are related to (w,w*) by a Fourier-Mellin transform. We can transform the single-valued harmonic polylogarithms to functions of (\nu,n) that incorporate harmonic sums, systematically through transcendental weight six. Combining this information with the four-loop results, we determine the eigenvalues of the BFKL kernel in the adjoint representation to NNLLA accuracy, and the MHV product of impact factors to NNNLLA accuracy, up to constants representing beyond-the-symbol terms and the one symbol-level constant. Remarkably, only derivatives of the polygamma function enter these results. Finally, the LLA approximation to the six-gluon NMHV amplitude is evaluated through ten loops.Comment: 71 pages, 2 figures, plus 10 ancillary files containing analytic expressions in Mathematica format. V2: Typos corrected and references added. V3: Typos corrected; assumption about single-Reggeon exchange made explici