538 research outputs found

    Generalized Metric Repair on Graphs

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    Many modern data analysis algorithms either assume or are considerably more efficient if the distances between the data points satisfy a metric. However, as real data sets are noisy, they often do not possess this fundamental property. For this reason, Gilbert and Jain [A. Gilbert and L. Jain, 2017] and Fan et al. [C. Fan et al., 2018] introduced the closely related sparse metric repair and metric violation distance problems. Given a matrix, representing all distances, the goal is to repair as few entries as possible to ensure they satisfy a metric. This problem was shown to be APX-hard, and an O(OPT^{1/3})-approximation was given, where OPT is the optimal solution size. In this paper, we generalize the problem, by describing distances by a possibly incomplete positively weighted graph, where again our goal is to find the smallest number of weight modifications so that they satisfy a metric. This natural generalization is more flexible as it takes into account different relationships among the data points. We demonstrate the inherent combinatorial structure of the problem, and give an approximation-preserving reduction from MULTICUT, which is hard to approximate within any constant factor assuming UGC. Conversely, we show that for any fixed constant ?, for the large class of ?-chordal graphs, the problem is fixed parameter tractable, answering an open question from previous work. Call a cycle broken if it contains an edge whose weight is larger than the sum of all its other edges, and call the amount of this difference its deficit. We present approximation algorithms, one depending on the maximum number of edges in a broken cycle, and one depending on the number of distinct deficit values, both quantities which may naturally be small. Finally, we give improved analysis of previous algorithms for complete graphs

    Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: Influence on Serum Lipids

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    The gap in mortality between patients with rheumatoid arthritis (RA) and the general population (1.5–3.0 fold risk) is increasing. This disparity is attributable mainly to cardiovascular disease (CVD), as the CVD risk is comparable to patients with diabetes mellitus. The purpose of this study is to determine whether borage seed oil rich in gamma-linolenic acid, fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or the combination of both oils are useful treatments for dyslipidemia in patients with RA. We randomized patients into a double blind, 18 month trial. Mixed effects models were used to compare trends over time in serum lipids. No significant differences were observed between the three groups: All three treatment groups exhibited similar meaningful improvement in the lipid profile at 9 and 18 months. When all groups were combined, these treatments significantly reduced total and LDL-cholesterol and triglycerides, increased HDL-cholesterol, and improved the atherogenic index. All improvements observed at 9 months persisted at 18 months (P < 0.001 verses baseline). Conclusion. Marine and botanical oils may be useful treatment for rheumatoid arthritis patients who are at increased risk for cardiovascular disease compared to the general population

    Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: Influence on Serum Lipids (poster)

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    Background: Over the past 30 years substantial progress has been made in the medical and surgical management of patients with rheumatoid arthritis (RA). Despite this progress, there is an increasing gap in mortality between patients with RA (1.5-3.0 fold risk) and the general population. This disparity is mainly attributable to cardiovascular disease (CVD) as the CVD risk is comparable in RA patients as to patients with diabetes mellitus. Although the reasons for this gap are not entirely clear, the traditional risk of abnormalities in lipid profiles appears to be enhanced by a chronic increase in inflammatory cytokines, resulting in accelerated atherosclerosis. Study Objective: The object of this study was to determine the effect of marine (fish oil) and botanical oils (borage oil) on lipids (TC, HDL, LDL, TG), a risk factor for cardiovascular disease in patients with RA. The main outcome (to be presented elsewhere) was to determine whether a combination of borage seed oil rich in gammalinolenic acid (GLA) and fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is superior to either oil alone for the treatment of RA. Population and Setting: The study was an 18 month randomized, double-masked comparison of borage seed oil, fish oil, and the combination of both oils in RA patients with active synovitis. Intervention: Patients received 3.5 gm omega-3 fatty acids daily in a 2.1gm EPA/1.4 gm DHA ratio (7 fish oil and 6 sunflower oil capsules daily); or 1.8 gm /d GLA (6 borage oil and 7 sunflower oil capsules /d); or 7 fish oil and 6 borage oil capsules daily (combination therapy). Discussion: Rheumatoid Arthritis (RA) is a chronic systemic inflammatory disease. Mediators of inflammation and prothrombotic factors contribute to endothelial dysfunction and development of cardiovascular disease in RA patients. Marine and botanical oils represent an excellent primary or secondary therapy for improvement of the cardiovascular risk management in RA. Patients taking these oils exhibit significant additional reductions in total and LDL-cholesterol, triglycerides, the TC/HDL ratio, and in the atherogenic index, and experience a significant increase in HDL-cholesterol. All of these improvements in the lipid profile were seen after 9 months of therapy, and increased after 18 months of oils administration. The overall dropout rate was 51%, and was similar across groups: 25 in the borage oil group, 28 in the fish oil group, and 22 in the combination group. Reasons for dropout were mainly gastrointestinal distress (belching, bloating, diarrhea, nausea, cramping), or an inability to swallow the large number of rather sizable capsules. This can be ameliorated by freezing the capsules and reducing their size. Among those evaluated for this study, compliance was 100%, assessed by pill counts. Learning Outcome: All treatments were safe, thus treatment of RA patients with one or a combination of these or similar oils should prove useful for reduction of cardiovascular risk in RA patients

    A mathematical model for top-shelf vertigo: the role of sedimenting otoconia in BPPV

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    Benign Paroxysmal Positional Vertigo (BPPV) is a mechanical disorder of the vestibular system in which calcite particles called otoconia interfere with the mechanical functioning of the fluid-filled semicircular canals normally used to sense rotation. Using hydrodynamic models, we examine the two mechanisms proposed by the medical community for BPPV: cupulolithiasis, in which otoconia attach directly to the cupula (a sensory membrane), and canalithiasis, in which otoconia settle through the canals and exert a fluid pressure across the cupula. We utilize known hydrodynamic calculations and make reasonable geometric and physical approximations to derive an expression for the transcupular pressure ΔPc\Delta P_c exerted by a settling solid particle in canalithiasis. By tracking settling otoconia in a two-dimensional model geometry, the cupular volume displacement and associated eye response (nystagmus) can be calculated quantitatively. Several important features emerge: 1) A pressure amplification occurs as otoconia enter a narrowing duct; 2) An average-sized otoconium requires approximately five seconds to settle through the wide ampulla, where ΔPc\Delta P_c is not amplified, which suggests a mechanism for the observed latency of BPPV; and 3) An average-sized otoconium beginning below the center of the cupula can cause a volumetric cupular displacement on the order of 30 pL, with nystagmus of order 22^\circ/s, which is approximately the threshold for sensation. Larger cupular volume displacement and nystagmus could result from larger and/or multiple otoconia.Comment: 15 pages, 5 Figures updated, to be published in J. Biomechanic

    Costs of Inducible Defence along a Resource Gradient

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    In addition to having constitutive defence traits, many organisms also respond to predation by phenotypic plasticity. In order for plasticity to be adaptive, induced defences should incur a benefit to the organism in, for example, decreased risk of predation. However, the production of defence traits may include costs in fitness components such as growth, time to reproduction, or fecundity. To test the hypothesis that the expression of phenotypic plasticity incurs costs, we performed a common garden experiment with a freshwater snail, Radix balthica, a species known to change morphology in the presence of molluscivorous fish. We measured a number of predator-induced morphological and behavioural defence traits in snails that we reared in the presence or absence of chemical cues from fish. Further, we quantified the costs of plasticity in fitness characters related to fecundity and growth. Since plastic responses may be inhibited under limited resource conditions, we reared snails in different densities and thereby levels of competition. Snails exposed to predator cues grew rounder and thicker shells, traits confirmed to be adaptive in environments with fish. Defence traits were consistently expressed independent of density, suggesting strong selection from predatory molluscivorous fish. However, the expression of defence traits resulted in reduced growth rate and fecundity, particularly with limited resources. Our results suggest full defence in predator related traits regardless of resource availability, and costs of defence consequently paid in traits related to fitness

    Optimizing the vertebrate vestibular semicircular canal: could we balance any better?

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    The fluid-filled semicircular canals (SCCs) of the vestibular system are used by all vertebrates to sense angular rotation. Despite masses spanning seven decades, all mammalian SCCs are nearly the same size. We propose that the SCC represents a sensory organ that evolution has `optimally designed'. Four geometric parameters are used to characterize the SCC, and `building materials' of given physical properties are assumed. Identifying physical and physiological constraints on SCC operation, we find that the most sensitive SCC has dimensions consistent with available data.Comment: 4 pages, 3 figure

    Zonal surface wind jets across the Red Sea due to mountain gap forcing along both sides of the Red Sea

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    Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 36 (2009): L19605, doi:10.1029/2009GL040008.Mesoscale atmospheric modeling over the Red Sea, validated by in-situ meteorological buoy data, identifies two types of coastal mountain gap wind jets that frequently blow across the longitudinal axis of the Red Sea: (1) an eastward-blowing summer daily wind jet originating from the Tokar Gap on the Sudanese Red Sea coast, and (2) wintertime westward-blowing wind-jet bands along the northwestern Saudi Arabian coast, which occur every 10–20 days and can last for several days when occurring. Both wind jets can attain wind speeds over 15 m s−1 and contribute significantly to monthly mean surface wind stress, especially in the cross-axis components, which could be of importance to ocean eddy formation in the Red Sea. The wintertime wind jets can cause significant evaporation and ocean heat loss along the northeastern Red Sea coast and may potentially drive deep convection in that region. An initial characterization of these wind jets is presented.Supported by Award Numbers USA 00001, USA 00002, and KSA 00011 made by KAUST

    The malaria candidate vaccine liver stage antigen-3 is highly conserved in Plasmodium falciparum isolates from diverse geographical areas

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    <p>Abstract</p> <p>Background</p> <p>A high level of genetic stability has been formerly identified in segments of the gene coding for the liver stage antigen-3 (LSA-3), a subunit vaccine candidate against <it>Plasmodium falciparum</it>. The exploration of <it>lsa-3 </it>polymorphisms was extended to the whole sequence of this large antigen in 20 clinical isolates from four geographical areas; Senegal, Comoro islands, Brazil and Thailand.</p> <p>Methods</p> <p>The whole 4680 bp genomic sequence of <it>lsa-3 </it>was amplified by polymerase chain reaction and sequenced. The clinical isolate sequences were aligned on the sequence of the laboratory reference <it>P. falciparum </it>strain 3D7.</p> <p>Results</p> <p>The non-repeated sequence of <it>lsa-3 </it>was very well conserved with only a few allelic variations scattered along the sequence. Interestingly, a formerly identified immunodominant region, employed for the majority of pre-clinical vaccine development, was totally conserved at the genetic level. The most significant variations observed were in the number and organization of tetrapeptide repeated units, but not in their composition, resulting in different lengths of these repeated regions. The shorter repeated regions were from Brazilian origin. A correlation between the geographical distribution of the parasites with single nucleotide polymorphisms was not detected.</p> <p>Conclusion</p> <p>The lack of correlation between allelic polymorphisms with a specific transmission pressure suggests that LSA-3 is a structurally constrained molecule. The unusual characteristics of the <it>lsa-3 </it>gene make the molecule an interesting candidate for a subunit vaccine against malaria.</p

    Cup Blocks the Precocious Activation of the Orb Autoregulatory Loop

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    Translational regulation of localized mRNAs is essential for patterning and axes determination in many organisms. In the Drosophila ovary, the germline-specific Orb protein mediates the translational activation of a variety of mRNAs localized in the oocyte. One of the Orb target mRNAs is orb itself, and this autoregulatory activity ensures that Orb proteins specifically accumulate in the developing oocyte. Orb is an RNA-binding protein and is a member of the cytoplasmic polyadenylation element binding (CPEB) protein family. We report here that Cup forms a complex in vivo with Orb. We also show that cup negatively regulates orb and is required to block the precocious activation of the orb positive autoregulatory loop. In cup mutant ovaries, high levels of Orb accumulate in the nurse cells, leading to what appears to be a failure in oocyte specification as a number of oocyte markers inappropriately accumulate in nurse cells. In addition, while orb mRNA is mislocalized and destabilized, a longer poly(A) tail is maintained than in wild type ovaries. Analysis of Orb phosphoisoforms reveals that loss of cup leads to the accumulation of hyperphosphorylated Orb, suggesting that an important function of cup in orb-dependent mRNA localization pathways is to impede Orb activation
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