Note On The Effectiveness OF Stochastic Optimization Algorithms For Robust Design

Robust design optimization (RDO) uses statistical decision theory and optimization techniques to optimize a design over a range of uncertainty (introduced by the manufacturing process and unintended uses). Since engineering ob jective functions tend to be costly to evaluate and prohibitively expensive to integrate (required within RDO), surrogates are introduced to allow the use of traditional optimization methods to find solutions. This paper explores the suitability of radically different (deterministic and stochastic) optimization methods to solve prototypical robust design problems. The algorithms include a genetic algorithm using a penalty function formulation, the simultaneous perturbation stochastic approximation (SPSA) method, and two gradient-based constrained nonlinear optimizers (method of feasible directions and sequential quadratic programming). The results show that the fully deterministic standard optimization algorithms are consistently more accurate, consistently more likely to terminate at feasible points, and consistently considerably less expensive than the fully nondeterministic algorithms

Epigallocatechin Gallate Regulates the Myeloid-Specific Transcription Factor PU1 in Macrophages

Our previous research demonstrated that PU.1 regulates expression of the genes involved in inflammation in macrophages. Selective knockdown of PU.1 in macrophages ameliorated LPS-induced acute lung injury (ALI) in bone marrow chimera mice. Inhibitors that block the transcriptional activity of PU.1 in macrophages have the potential to mitigate the pathophysiology of LPS-induced ALI. However, complete inactivation of PU.1 gene disrupts normal myelopoiesis. Although the green tea polyphenol Epigallocatechin gallate (EGCG) has been shown to regulate inflammatory genes in various cell types, it is not known if EGCG alters the transcriptional activity of PU.1 protein. Using Schrodinger Glide docking, we have identified that EGCG binds with PU.1 protein, altering its DNA-binding and self-dimerization activity. In silico analysis shows that EGCG forms Hydrogen bonds with Glutamic Acid 209, Leucine 250 in DNA binding and Lysine 196, Tryptophan 193, and Leucine 182 in the self-dimerization domain of the PU.1 protein. Experimental validation using mouse bone marrow-derived macrophages (BMDM) confirmed that EGCG inhibits both DNA binding by PU.1 and self-dimerization. Importantly, EGCG had no impact on expression of the total PU.1 protein levels but significantly reduced expression of various inflammatory genes and generation of ROS. In summary, we report that EGCG acts as an inhibitor of the PU.1 transcription factor in macrophages

Algorithm XXX: SHEPPACK: Modified Shepard Algorithm for Interpolation of Scattered Multivariate Data

Scattered data interpolation problems arise in many applications. Shepard’s method for constructing a global interpolant by blending local interpolants using local-support weight functions usually creates reasonable approximations. SHEPPACK is a Fortran 95 package containing five versions of the modified Shepard algorithm: quadratic (Fortran 95 translations of Algorithms 660, 661, and 798), cubic (Fortran 95 translation of Algorithm 791), and linear variations of the original Shepard algorithm. An option to the linear Shepard code is a statistically robust fit, intended to be used when the data is known to contain outliers. SHEPPACK also includes a hybrid robust piecewise linear estimation algorithm RIPPLE (residual initiated polynomial-time piecewise linear estimation) intended for data from piecewise linear functions in arbitrary dimension m. The main goal of SHEPPACK is to provide users with a single consistent package containing most existing polynomial variations of Shepard’s algorithm. The algorithms target data of different dimensions. The linear Shepard algorithm, robust linear Shepard algorithm, and RIPPLE are the only algorithms in the package that are applicable to arbitrary dimensional data

Tuberculosis in children in India-II: Chemotherapy for tuberculosis

Tubercle bacilli readily become resistant to the common drugs, and resistant bacilli are more likely to proliferate if they are present in the patient at the start of treatment. So always use more than one drug. The only possible exception is prophylaxis for an asymptomatic case with a normal X-ray. CAUTION! (1) Never give intermittent (twice or thrice weekly) treatment unless every dose can be supervised by a health worker. Daily treatment is usually mandatory. (2) When you give more than one drug, give them both at the same time, so that high blood levels coincide; do not give one drug daily and the other drug less often. THE DOSES of the commonly used drugs for daily and intermittent treatment in children and adults are: lsoniazid (H) 5 mg/kg/24 hours if he is moderately ill and 10 mg/kg/24 hours if he is severely ill. The dose for a twice weekly course is 15 mg/kg. CAUTION! Opinions on the dose of isoniazid vary. Some consider 10 mg/kg/24 hours too much for an Indian child and always give 5 mg. Rifampicin (R) 10 mg/kg/24 hours, or 10 mg/kg twice weekly. Pyrazinamide (Z) 35 mg/kg/24 hours, 75 mg/kg twice weekly or 50 mg/kg thrice weekly, is an important drug for short course treatment, so try to include it whenever it is mentioned in the regimes below. Streptomycin (S) 10-20 mg/kg/24 hours, or 40 mg/kg twice weekly, to a total of not more than 0.75 g. Streptomycin is painful, so avoid it if you can. If you give it, inject in different places each day, because repeated injections into the same site are painful. Ethambutol (E) 25 mg/kg/24 hours for 2 months, then 15 mg/kg/24 hours. Avoid ethambutol in younger children (under 12); they are unable to complain of the early symptoms of retrobulbar neuritis (blindness). Thiacetazone (T) 4 mg/kg/24 hours to a maximum Of 150 mg; unsuitable for intermittent treatment

Tuberculosis in children in India-I

Tuberculosis is different in children. It involves many organs, instead of being the predominantly respiratory disease that it usually is in adults. Fortunately, it readily responds to treatment–if you diagnose it early enough and treat it for long enough! This is the problem. Unfortunately, tuberculosis causes such non-specific symptoms and signs, and you are so seldom able to isolate bacilli, that you may never be sure of the diagnosis. Even experts sometimes disagree. In India particularly, it is a disease of the poorest of the poor, but even in them it causes only a small proportion of their burden of morbidity. The great problem is to reach those infected. Of every thousand Indians, seven children and about twenty adults have active tuberculosis, and five of these adults are sputum positive. Only about half the 9 million in the community at any one time are ever diagnosed, and of these only about 13% complete their treatment, so there is a huge pool of infectious cases, half a million of whom die each year. Fortunately, the incidence of tuberculosis among children reporting to hospital is slowly decreasing, probably largely due to improved coverage with BCG

The Calcineurin-NFATc Pathway Modulates the Lipid Mediators in BAL Fluid Extracellular Vesicles, Thereby Regulating Microvascular Endothelial Cell Barrier Function

Extracellular vesicles mediate intercellular communication by transporting biologically active macromolecules. Our prior studies have demonstrated that the nuclear factor of activated T cell cytoplasmic member 3 (NFATc3) is activated in mouse pulmonary macrophages in response to lipopolysaccharide (LPS). Inhibition of NFATc3 activation by a novel cell-permeable calcineurin peptide inhibitor CNI103 mitigated the development of acute lung injury (ALI) in LPS-treated mice. Although pro-inflammatory lipid mediators are known contributors to lung inflammation and injury, it remains unclear whether the calcineurin-NFATc pathway regulates extracellular vesicle (EV) lipid content and if this content contributes to ALI pathogenesis. In this study, EVs from mouse bronchoalveolar lavage fluid (BALF) were analyzed for their lipid mediators by liquid chromatography in conjunction with mass spectrometry (LC-MS/MS). Our data demonstrate that EVs from LPS-treated mice contained significantly higher levels of arachidonic acid (AA) metabolites, which were found in low levels by prior treatment with CNI103. The catalytic activity of lung tissue cytoplasmic phospholipase A2 (cPLA2) increased during ALI, correlating with an increased amount of arachidonic acid (AA) in the EVs. Furthermore, ALI is associated with increased expression of cPLA2, cyclooxygenase 2 (COX2), and lipoxygenases (5-LOX, 12-LOX, and 15-LOX) in lung tissue, and pretreatment with CNI103 inhibited the catalytic activity of cPLA2 and the expression of cPLA2, COX, and LOX transcripts. Furthermore, co-culture of mouse pulmonary microvascular endothelial cell (PMVEC) monolayer and NFAT-luciferase reporter macrophages with BALF EVs from LPS-treated mice increased the pulmonary microvascular endothelial cell (PMVEC) monolayer barrier permeability and luciferase activity in macrophages. However, EVs from CNI103-treated mice had no negative impact on PMVEC monolayer barrier integrity. In summary, BALF EVs from LPS-treated mice carry biologically active NFATc-dependent, AA-derived lipids that play a role in regulating PMVEC monolayer barrier function

Impact assessment and adaptation to climate change of plantations in Sri Lanka

This report documents the work undertaken by the IRI, FECT, NRMS and University of Peradeniya as part of the overall project. Separate reports were prepared by the Tea Research Institute, Coconut Research Institute and the Department of Meteorology in Sri Lanka. The work at IRI, FECT and NRMS has proceeded satisfactorily. The work was in the domain of climate and climate change, crop-climate impact analysis and contributions to synthesis. We have contributed significantly in terms of research output and in capacity building, which were the goals of the AIACC project

Programmatic use of molecular xenomonitoring at the level of evaluation units to assess persistence of lymphatic filariasis in Sri Lanka

BACKGROUND:Sri Lanka's Anti Filariasis Campaign distributed 5 rounds of mass drug administration (MDA with DEC plus albendazole) to all endemic regions in the country from 2002-2006. Post-MDA surveillance results have generally been encouraging. However, recent studies have documented low level persistence of Wuchereria bancrofti in Galle district based on comprehensive surveys that include molecular xenomonitoring (MX, detection of filarial DNA in mosquitoes) results. The purposes of this study were to demonstrate the use of MX in large evaluation units (EUs) and to field test different mosquito sampling schemes. METHODOLOGY/PRINCIPAL FINDINGS:Galle district (population 1.1 million) was divided into two EUs. These included a coastal EU with known persistent LF and an inland EU with little persistent LF. Mosquitoes were systematically sampled from ~300 trap locations in 30 randomly selected clusters (health administrative units) per EU. Approximately 28,000 Culex quinquefasciatus were collected with gravid traps and tested for filarial DNA by qPCR. 92/625 pools (14.7%) from the coastal EU and 8/583 pools (1.4%) from the inland EU were positive for filarial DNA. Maximum likelihood estimates (MLE) for filarial DNA rates were essentially the same when the same number of mosquito pools were collected and tested from 75, 150, or 300 trap sites (range 0.61-0.78% for the coastal EU and 0.04-0.07% for the inland EU). The ability to use a smaller number of trap sites reduces the cost and time required for mosquito sampling. CONCLUSIONS/SIGNIFICANCE:These results suggest there is widespread persistence of W. bancrofti infection in the coastal Galle EU 8 years after the last round of MDA in 2006, and this is consistent with other data from the district. This study has shown that MX can be used by national programs to assess and map the persistence of W. bancrofti at the level of large EUs in areas with Culex transmission