lp-Recovery of the Most Significant Subspace among Multiple Subspaces with Outliers

We assume data sampled from a mixture of d-dimensional linear subspaces with spherically symmetric distributions within each subspace and an additional outlier component with spherically symmetric distribution within the ambient space (for simplicity we may assume that all distributions are uniform on their corresponding unit spheres). We also assume mixture weights for the different components. We say that one of the underlying subspaces of the model is most significant if its mixture weight is higher than the sum of the mixture weights of all other subspaces. We study the recovery of the most significant subspace by minimizing the lp-averaged distances of data points from d-dimensional subspaces, where p>0. Unlike other lp minimization problems, this minimization is non-convex for all p>0 and thus requires different methods for its analysis. We show that if 0<p<=1, then for any fraction of outliers the most significant subspace can be recovered by lp minimization with overwhelming probability (which depends on the generating distribution and its parameters). We show that when adding small noise around the underlying subspaces the most significant subspace can be nearly recovered by lp minimization for any 0<p<=1 with an error proportional to the noise level. On the other hand, if p>1 and there is more than one underlying subspace, then with overwhelming probability the most significant subspace cannot be recovered or nearly recovered. This last result does not require spherically symmetric outliers.Comment: This is a revised version of the part of 1002.1994 that deals with single subspace recovery. V3: Improved estimates (in particular for Lemma 3.1 and for estimates relying on it), asymptotic dependence of probabilities and constants on D and d and further clarifications; for simplicity it assumes uniform distributions on spheres. V4: minor revision for the published versio

Wilson loops stability in the gauge/string correspondence

We study the stability of some classical string worldsheet solutions employed for computing the potential energy between two static fundamental quarks in confining and non-confining gravity duals. We discuss the fixing of the diffeomorphism invariance of the string action, its relation with the fluctuation orientation and the interpretation of the quark mass substraction worldsheet needed for computing the potential energy in smooth (confining) gravity background. We consider various dual gravity backgrounds and show by a numerical analysis the existence of instabilities under linear fluctuations for classical string embedding solutions having positive length function derivative $L'(r_0)>0$. Finally we make a brief discussion of 't Hooft loops in non-conformal backgrounds.Comment: 34 pages, 36 figures. Reference added. Final version JHEP accepte

A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in patients aged 70 and over with advanced non-small cell lung cancer

Background: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR).Methods: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes.Results: Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail.Conclusions: The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy.Trial Registration: ClinicalTrials.gov NCT01011075. © 2012 Bauman et al.; licensee BioMed Central Ltd

Spatio-temporal distribution of pyrethroids in soil in Mediterranean paddy fields

[EN] The demand of rice by the increase in population in many countries has intensified the application of pesticides and the use of poor quality water to irrigate fields. The terrestrial environment is one compartment affected by these situations, where soil is working as a reservoir, retaining organic pollutants. Therefore, it is necessary to develop methods to determine insecticides in soil and monitor susceptible areas to be contaminated, applying adequate techniques to remediate them. Materials and methods This study investigates the occurrence of ten pyrethroid insecticides (PYs) and its spatio-temporal variance in soil at two different depths collected in two periods (before plow and during rice production), in a paddy field area located in the Mediterranean coast. Pyrethroids were quantified using gas chromatography mass spectrometry (GC MS) after ultrasound-assisted extraction with ethyl acetate. The results obtained were assessed statistically using non-parametric methods, and significant statistical differences (p&#8201;<&#8201;0.05) in pyrethroids content with soil depth and proximity to wastewater treatment plants were evaluated. Moreover, a geographic information system (GIS) was used to monitor the occurrence of PYs in paddy fields and detect risk areas. Results and discussion Pyrethroids were detected at concentrations &#8804;57.0 ng g&#8722;1 before plow and &#8804;62.3 ng g&#8722;1 during rice production, being resmethrin and cyfluthrin the compounds found at higher concentrations in soil. Pyrethroids were detected mainly at the top soil, and a GIS program was used to depict the obtained results, showing that effluents from wastewater treatment plants (WWTPs) were the main sources of soil contamination. No toxic effects were expected to soil organisms, but it is of concern that PYs may affect aquatic organisms, which represents the worst case scenario. Conclusions A methodology to determine pyrethroids in soil was developed to monitor a paddy field area. The use of water from WWTPs to irrigate rice fields is one of the main pollution sources of pyrethroids. It is a matter of concern that PYs may present toxic effects on aquatic organisms, as they can be desorbed from soil. Phytoremediation may play an important role in this area, reducing the possible risk associated to PYs levels in soil.Authors wish to thank INIA for the predoctoral fellowship (R. Aznar) and Spanish Ministry of Economy and Competitiveness RTA2014-00012-C03-01 for financial support and Jonathan Villanueva Martin for his contribution to this work.Aznar, R.; Moreno-Ramón, H.; Albero, B.; Sánchez Brunete, C.; Tadeo, JL. (2016). Spatio-temporal distribution of pyrethroids in soil in Mediterranean paddy fields. Journal of Soils and Sediments. 17(5):1503-1513. https://doi.org/10.1007/s11368-016-1417-2S15031513175Albaseer SS, Rao RN, Swamy YV, Mukkanti K (2010) An overview of sample preparation and extraction of synthetic pyrethroids from water, sediment and soil. J Chromatogr A 1217(35):5537–5554Alonso MB, Feo ML, Corcellas C, Vidal LG, Bertozzi CP, Marigo J, Secchi ER, Bassoi M, Azevedo AF, Dorneles PR, Torres JPM, Lailson-Brito J, Malm O, Eljarrat E, Barcelo D (2012) Pyrethroids: a new threat to marine mammals? Environ Int 47:99–106Amweg EL, Weston DP, Ureda NM (2005) Use and toxicity of pyrethroid pesticides in the Central Valley, California, USA. Environ Toxicol Chem 24(4):966–972Arias-Estevez M, Lopez-Periago E, Martinez-Carballo E, Simal-Gandara J, Mejuto JC, Garcia-Rio L (2008) The mobility and degradation of pesticides in soils and the pollution of groundwater resources. Agric Eco Environ 123(4):247–260Aznar R, Albero B, Sanchez-Brunete C, Miguel E, Tadeo JL (2014) Multiresidue analysis of insecticides and other selected environmental contaminants in poultry manure by gas chromatography/mass spectrometry. J AOAC Int 97(4):978–986Campo J, Masia A, Blasco C, Pico Y (2013) Occurrence and removal efficiency of pesticides in sewage treatment plants of four Mediterranean River Basins. J Hazard Mater 263:146–157European Commission (2002) Review report for the active substance Cyfluthrin, 6843/VI/97-finalEuropean Commission (2004) Review report for the active substance α-Cypermethrin, SANCO/4335/2000-finalEuropean Commission (2005) Review report for the active substance Esfenvalerate, 6846/VI/97-finalFeo ML, Ginebreda A, Eljarrat E, Barcelo D (2010) Presence of pyrethroid pesticides in water and sediments of Ebro River Delta. J Hydrol 393(3-4):156–162Fojut TL, Palumbo AJ, Tjeerdema RS (2012) Aquatic life water quality criteria derived via the UC Davis method: II. Pyrethroid insecticides. Rev Environ Contam Toxicol 216:51–103Gan J, Lee SJ, Liu WP, Haver DL, KAbashima JN (2005) Distribution and persistence of pyrethroids in runoff sediments. J Environ Qual 34:836–841Hill IR (1985) Aquatic organisms and pyrethroids. Pestic Sci 27:429–465Huang LM, Thompson A, Zhang GL, Chen LM, Han GZ, Gong ZT (2015) The use of chronosequences in studies of paddy soil evolution: a review. Geoderma 237:199–210Katagi T (2004) Photodegradation of pesticides on plant and soil surfaces. Rev Environ Contam Toxicol 182:1–189Laskowski DA (2002) Physical and chemical properties of pyrethroids. Rev Environ Contam Toxicol 174:49–170Mahabali S, Spagnoghe P (2014) Mitigation of two insecticides by wetlands plants: feasibility study for the treatment of agricultural runoff in Suriname (South America). Water Air Soil Pollut 225:1771Maund SJ, Hamer MJ, Lane MCG, Farrelly E, Rapley JH, Goggin UM, Gentle WE (2002) Partitioning, bioavailability, and toxicity of the pyrethroid insecticide cypermethrin in sediments. Environ Toxicol Chem 21(1):9–15Maund SJ, Campbell PJ, Giddings JM, Hamer MJ, Henry K, Pilling ED, Warinton JS, Wheeler JR (2012) Ecotoxicology of synthetic pyrethroids. Top Curr Chem 314:137–165Money E, Carter GP, Serre ML (2009) Using river distances in the space/time estimation of dissolved oxygen along two impaired river networks in New Jersey. Water Res 43(7):1948–1958Moore MT, Cooper CM, Smith S, Jr Cullum RF, Knight SS, Locke MA, Bennett ER (2009) Mitigation of two pyrethroid insecticides in Mississippi Delta constructed wetland. Environ Pollut 157:250–256Moreno-Ramón H, Marqués-Mateu A, Ibáñez-Asensio S, Gisbert JM (2015) Wetland soils under rice management and seawater intrusion: characterization and classification. Spa J Soil Sci 5(2):111–129Nawaz MF, Bourrie G, Trolard F, Mouret JC, Henry P (2013) Effects of agronomic practices on the physico-chemical properties of soil waters in rice culture. Turk J Agric For 37(2):195–202Oros DR, Werner I (2005) Pyrethroid insecticides: an analysis of use patterns, distributions, potential toxicity and fate in the Sacramento-San Joaquin Delta and Central Valley. White Paper for the Interagency Ecological Program. SFEI Contribution 415. San Francisco Estuary Institute, Oakland, CAPascual-Aguilar J, Andreu V, Gimeno-Garcia E, Pico Y (2015) Current anthropogenic pressures on agro-ecological protected coastal wetlands. Sci Total Environ 03:190–199Soil Survey Staff (2014a) Soil survey field and laboratory methods manual. Soil survey investigations report no. 51, version 2.0. In: Burt R, Soil Survey Staff (eds). U.S. Department of Agriculture, Natural Resources Conservation Service, Washington, p 407Soil Survey Staff (ed) (2014b) Keys to soil taxonomy, 12th edn. USDA-Natural Resources Conservation Service, Washington, p 372Song Y, Kai J, Song X, Zhang W, Li L (2015) Long-term toxic effects of deltamethrin and fenvalerate in soil. J Hazard Mater 289:158–164Weston DP, Holmes RW, You J, Lydy MJ (2005) Aquatic toxicity due to residential use of pyrethroid insecticides. Environ Sci Technol 39(24):9778–9784Weston DP, Ramil HL, Lydy MJ (2013) Pyrethroid insecticides in municipal wastewater. Environ Toxicol Chem 32(11):2460–2468Zhou JL, Rowland S, Mantoura RFC (1995) Partition of synthetic pyrethroid insecticides between dissolved and particulate phases. Water Res 29:1023–110

Beyond aridification: multiple explanations for the elevated diversification of cacti in the New World Succulent Biome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106989/1/nph12752.pd

Whole Genome Characterization of the Mechanisms of Daptomycin Resistance in Clinical and Laboratory Derived Isolates of Staphylococcus aureus

Background: Daptomycin remains one of our last-line anti-staphylococcal agents. This study aims to characterize the genetic evolution to daptomycin resistance in S. aureus. Methods: Whole genome sequencing was performed on a unique collection of isogenic, clinical (21 strains) and laboratory (12 strains) derived strains that had been exposed to daptomycin and developed daptomycin-nonsusceptibility. Electron microscopy (EM) and lipid membrane studies were performed on selected isolates. Results: On average, six coding region mutations were observed across the genome in the clinical daptomycin exposed strains, whereas only two mutations on average were seen in the laboratory exposed pairs. All daptomycin-nonsusceptible strains had a mutation in a phospholipid biosynthesis gene. This included mutations in the previously described mprF gene, but also in other phospholipid biosynthesis genes, including cardiolipin synthase (cls2) and CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase (pgsA). EM and lipid membrane composition analyses on two clinical pairs showed that the daptomycin-nonsusceptible strains had a thicker cell wall and an increase in membrane lysyl-phosphatidylglycerol. Conclusion: Point mutations in genes coding for membrane phospholipids are associated with the development of reduced susceptibility to daptomycin in S. aureus. Mutations in cls2 and pgsA appear to be new genetic mechanisms affecting daptomycin susceptibility in S. aureus

I–II Loop Structural Determinants in the Gating and Surface Expression of Low Voltage-Activated Calcium Channels

The intracellular loops that interlink the four transmembrane domains of Ca2+- and Na+-channels (Cav, Nav) have critical roles in numerous forms of channel regulation. In particular, the intracellular loop that joins repeats I and II (I–II loop) in high voltage-activated (HVA) Ca2+ channels possesses the binding site for Cavβ subunits and plays significant roles in channel function, including trafficking the α1 subunits of HVA channels to the plasma membrane and channel gating. Although there is considerable divergence in the primary sequence of the I–II loop of Cav1/Cav2 HVA channels and Cav3 LVA/T-type channels, evidence for a regulatory role of the I–II loop in T-channel function has recently emerged for Cav3.2 channels. In order to provide a comprehensive view of the role this intracellular region may play in the gating and surface expression in Cav3 channels, we have performed a structure-function analysis of the I–II loop in Cav3.1 and Cav3.3 channels using selective deletion mutants. Here we show the first 60 amino acids of the loop (post IS6) are involved in Cav3.1 and Cav3.3 channel gating and kinetics, which establishes a conserved property of this locus for all Cav3 channels. In contrast to findings in Cav3.2, deletion of the central region of the I–II loop in Cav3.1 and Cav3.3 yielded a modest increase (+30%) and a reduction (−30%) in current density and surface expression, respectively. These experiments enrich our understanding of the structural determinants involved in Cav3 function by highlighting the unique role played by the intracellular I–II loop in Cav3.2 channel trafficking, and illustrating the prominent role of the gating brake in setting the slow and distinctive slow activation kinetics of Cav3.3

Kindlins, Integrin Activation and the Regulation of Talin Recruitment to αIIbβ3

Talins and kindlins bind to the integrin β3 cytoplasmic tail and both are required for effective activation of integrin αIIbβ3 and resulting high-affinity ligand binding in platelets. However, binding of the talin head domain alone to β3 is sufficient to activate purified integrin αIIbβ3 in vitro. Since talin is localized to the cytoplasm of unstimulated platelets, its re-localization to the plasma membrane and to the integrin is required for activation. Here we explored the mechanism whereby kindlins function as integrin co-activators. To test whether kindlins regulate talin recruitment to plasma membranes and to αIIbβ3, full-length talin and kindlin recruitment to β3 was studied using a reconstructed CHO cell model system that recapitulates agonist-induced αIIbβ3 activation. Over-expression of kindlin-2, the endogenous kindlin isoform in CHO cells, promoted PAR1-mediated and talin-dependent ligand binding. In contrast, shRNA knockdown of kindlin-2 inhibited ligand binding. However, depletion of kindlin-2 by shRNA did not affect talin recruitment to the plasma membrane, as assessed by sub-cellular fractionation, and neither over-expression of kindlins nor depletion of kindlin-2 affected talin interaction with αIIbβ3 in living cells, as monitored by bimolecular fluorescence complementation. Furthermore, talin failed to promote kindlin-2 association with αIIbβ3 in CHO cells. In addition, purified talin and kindlin-3, the kindlin isoform expressed in platelets, failed to promote each other's binding to the β3 cytoplasmic tail in vitro. Thus, kindlins do not promote initial talin recruitment to αIIbβ3, suggesting that they co-activate integrin through a mechanism independent of recruitment