On the Milnor formula in arbitrary characteristic

The Milnor formula $\mu=2\delta-r+1$ relates the Milnor number $\mu$, the double point number $\delta$ and the number $r$ of branches of a plane curve singularity. It holds over the fields of characteristic zero. Melle and Wall based on a result by Deligne proved the inequality $\mu\geq 2\delta-r+1$ in arbitrary characteristic and showed that the equality $\mu=2\delta-r+1$ characterizes the singularities with no wild vanishing cycles. In this note we give an account of results on the Milnor formula in characteristic $p$. It holds if the plane singularity is Newton non-degenerate (Boubakri et al. Rev. Mat. Complut. (2010) 25) or if $p$ is greater than the intersection number of the singularity with its generic polar (Nguyen H.D., Annales de l'Institut Fourier, Tome 66 (5) (2016)). Then we improve our result on the Milnor number of irreducible singularities (Bull. London Math. Soc. 48 (2016)). Our considerations are based on the properties of polars of plane singularities in characteristic $p$.Comment: 18 page

Leishmania isoenzyme polymorphisms in Ecuador: Relationships with geographic distribution and clinical presentation

Background: Determinants of the clinical presentation of the leishmaniases are poorly understood but Leishmania species and strain differences are important. To examine the relationship between clinical presentation, species and isoenzyme polymorphisms, 56 Leishmania isolates from distinct presentations of American tegumentary leishmaniasis (ATL) from Ecuador were analyzed. Methods: Isolates were characterized by multilocus enzyme electrophoresis for polymorphisms of 11 isoenzymes. Patients were infected in four different ecologic regions: highland and lowland jungle of the Pacific coast, Amazonian lowlands and Andean highlands. Results: Six Leishmania species constituting 21 zymodemes were identified: L. (Viannia) panamensis (21 isolates, 7 zymodemes), L. (V.) guyanensis (7 isolates, 4 zymodemes), L. (V.) braziliensis (5 isolates, 3 zymodemes), L. (Leishmania) mexicana (11 isolates, 4 zymodemes), L. (L.) amazonensis (10 isolates, 2 zymodemes) and L. (L.) major (2 isolates, 1 zymodeme). L. panamensis was the species most frequently identified in the Pacific region and was associated with several clinical variants of cutaneous disease (CL); eight cases of leishmaniasis recidiva cutis (LRC) found in the Pacific highlands were associated with 3 zymodemes of this species. Mucocutaneous leishmaniasis found only in the Amazonian focus was associated with 3 zymodemes of L. braziliensis. The papular variant of CL, Uta, found in the Andean highlands was related predominantly with a single zymodeme of L. mexicana. Conclusion: Our data show a high degree of phenotypic variation within species, and some evidence for associations between specific variants of ATL (i.e. Uta and LRC) and specific Leishmania zymodemes. This study further defines the geographic distribution of Leishmania species and clinical variants of ATL in Ecuador

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

ICAM-1 nanoclusters regulate hepatic epithelial cell polarity by leukocyte adhesion-independent control of apical actomyosin

Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with, and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1_KO human hepatic cells, liver organoids from ICAM-1_KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures. We identified the scaffolding protein EBP50/NHERF1/ SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell– cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress

Mechanical properties of double-layer and graded composite coatings of YSZ obtained by atmospheric plasma spraying

Double-layer and graded composite coatings of yttria-stabilized zirconia were sprayed on metallic substrates by atmospheric plasma spray. The coating architecture was built up by combining two different feedstocks: one micro- and one nanostructured. Microstructural features and mechanical properties (hardness and elastic modulus) of the coatings were determined by FE-SEM microscopy and nanoindentation technique, respectively. Additional adherence and scratch tests were carried out in order to assess the failure mechanisms occurring between the layers comprising the composites. Microstructural inspection of the coatings confirms the two-zone microstructure. This bimodal microstructure which is exclusive of the layer obtained from the nanostructured feedstock negatively affects the mechanical properties of the whole composite. Nanoindentation tests suitably reproduce the evolution of mechanical properties through coatings thickness on the basis of the position and/or amount of nanostructured feedstock used in the depositing layer. Adhesion and scratch tests show the negative effect on the coating adhesion of layer obtained from the nanostructured feedstock when this layer is deposited on the bond coat. Thus, the poor integrity of this layer results in lower normal stresses required to delaminate the coating in the adhesion test as well as minor critical load registered by using the scratch test.This work has been supported by the Spanish Ministry of Science and Innovation (Project MAT2012-38364-C03) and co-funded by ERDF (European Regional Development Funds).Carpio-Cobo, P.; Rayón Encinas, E.; Salvador Moya, MD.; Lusvarghi, L.; Sanchez, E. (2016). Mechanical properties of double-layer and graded composite coatings of YSZ obtained by atmospheric plasma spraying. Journal of Thermal Spray Technology. 25(4):778-787. https://doi.org/10.1007/s11666-016-0390-zS778787254Y.S. Tian, C.Z. Chen, D.Y. Wang, and J.I. Quianmao, Recent Developments in Zirconia Thermal Barrier Coatings, Surf. Rev. Lett., 2005, 12, p 369-378S. Sampath, U. Schulz, M.O. Jarligo, and S. Kuroda, Processing Science of Advanced Thermal-Barrier Systems, MRS Bull., 2012, 37(10), p 903-910D.R. Clarke, M. Oeschsner, and N.P. Padture, Thermal-Barrier Coatings for More Efficient Gas-Turbine Engines, MRS Bull., 2012, 37(10), p 891-898A. Feuersein, J. Knapp, T. Taylor, A. Ashary, A. Bolcavage, and N. Hitchman, Technical and Economical Aspects of Current Thermal Barrier Coating Systems for Gas Turbine Engines by Thermal Spray and EBPVD: A Review, J. Therm. Spray Technol., 2008, 17(2), p 199-213R.S. Lima and B.R. Marple, Thermal Spray Coatings Engineered from Nanostructured Ceramic Agglomerated Powders for Structural, Thermal Barrier and Biomedical Applications: A Review, J. Therm. Spray Technol., 2007, 16(1), p 40-63P. Fauchais, G. Montavon, R.S. Lima, and B.R. Marple, Engineering a New Class of Thermal Spray Nano-based Microstructures from Agglomerated Nanostructured Particles, Suspensions and Solutions: An Invited Review, J. Phys. D Appl. Phys., 2011, 44(9), p 093001P. Carpio, Q. Blochet, B. Pateyron, L. Pawlowski, M.D. Salvador, A. Borrell, and E. Sánchez, Correlation of Thermal Conductivity of Suspension Plasma Sprayed Yttira Stabilized Zirconia Coatings with some Microstructural Effects, Mater. Lett., 2013, 107, p 370-373R. Vassen, A. Stuke, and D. Stöver, Recent Developments in the Field of Thermal Barrier Coatings, J. Therm. Spray Technol., 2009, 18(2), p 181-186H. Dai, X. Zhong, J. Li, Y. Zhang, J. Meng, and X. Cao, Thermal Stability of Double-Ceramic-Layer Thermal Barrier Coatings with Various Coating Thickness, Mater. Sci. Eng. A—Struct., 2006, 433(1), p 1–7V. Viswanathan, G. Dwivedi, and S. Sampath, Multimaterial Thermal Barrier Coating Systems: Design, Synthesis, and Performance Assessment, J. Am. Ceram. Soc., 2015, 98(6), p 1769-1777M. Saremi and Z. Valefi, Thermal and Mechanical Properties of Nano-YSZ-Alumina Functionally Graded Coatings Deposited by Nano-agglomerated Powder Plasma Spraying, Ceram. Int., 2014, 40(8), p 13453-13459A. Portinham, V. Teixeira, J. Carneiro, J. Martins, M.F. Costa, R. Vassen, and D. Stoever, Characterization of Thermal Barrier Coatings with a Gradient Porosity, Surf. Coat. Technol., 2005, 195(2), p 245-251P. Carpio, E. Bannier, M.D. Salvador, R. Benavente, and E. Sánchez, Multilayer and Particle Size-Graded YSZ Coatings Obtained by Plasma Spraying of Micro- and Nanostructured Feedstocks, J. Therm. Spray Technol., 2014, 23(8), p 1362-1372S. Nath, I. Manna, and J.D. Majumdar, Nanomechanical Behavior of Yttria Stabilized Zirconia (YSZ) Based Thermal Barrier Coating, Ceram. Int., 2015, 41(4), p 5247-5256P. Carpio, E. Rayón, L. Pawlowski, A. Cattini, R. Benavente, E. Bannier, M.D. Salvador, and E. Sánchez, Microstructure and Indentation Mechanical Properties of YSZ Nanostructured Coatings Obtained by Suspension Plasma Spraying, Surf. Coat. Technol., 2013, 220, p 237-243H.B. Guo, H. Murakami, and S. Kuroda, Effect of Hollow Spherical Powder Size Distribution on Porosity and Segmentation Cracks in Thermal Barrier Coatings, J. Am. Ceram. Soc., 2006, 89(12), p 3797-3804R.S. Lima, A. Kucuk, and C.C. Berndt, Integrity of Nanostructured Partially Stabilized Zirconia After Plasma Spray Processing, Mater. Sci. Eng. A, 2001, 313(1), p 75-82E. Rayón, V. Bonache, M.D. Salvador, and E. Sánchez, Hardness and Young’s Modulus Distributions in Atmospheric Plasma Sprayed WC-Co Coatings Using Nanoindentation, Surf. Coat. Technol., 2011, 205(17), p 4192-4197J.A. Wollmershauser, B.N. Feigelson, E.P. Gorzkowski, C.T. Ellis, R. Goswami, S.B. Qadri, J.G. Tischler, F.J. Kub, and R.K. Everett, An Extend Hardness Limit in Bulk Nanoceramics, Acta Mater., 2014, 69, p 9-16L. Wang, Y. Wang, X.G. Sun, J.Q. He, Z.Y. Pan, and C.H. Wang, Microstructure and Indentation Mechanical Properties of Plasma Sprayed Nano-Bimodal and Conventional ZrO2-8 wt% Y2O3 Thermal Barrier Coatings, Vacuum, 2012, 86(8), p 1174-1185G.S. Barroso, W. Krenkel, and G. Motz, Low Thermal Conductivity Coating System for Application up to 1000 °C by Simple PDC Processing with Active and Passive Fillers, J. Eur. Ceram. Soc., 2015, 35(12), p 3339-3348R. Ghasemi, R. Shoja-Razavi, R. Mozafarinia, H. Jamali, M. Hajizadh-Oghaz, and R. Ahmadi-Pidani, The Influence of Laser Treatment on Hot Corrosion Behavior of Plasma-Sprayed Nanostructured Yttria Stabilized Zirconia Thermal Barrier Coatings, J. Eur. Ceram. Soc., 2014, 34(8), p 2013-2021E. Rayón, V. Bonache, M.D. Salvador, E. Bannier, E. Sánchez, A. Denoirjean, and H. Ageorges, Nanoindentation Study of the Mechanical and Damage Behaviour of Suspension Plasma Sprayed TiO2 Coatings, Surf. Coat. Technol., 2012, 206(10), p 2655-2660J.J. Roa, E. Jiménez-Piqué, R. Martínez, G. Ramírez, J.M. Tarragó, R. Rodríguez, and L. Llanes, Contact Damage and Fracture Micromechanisms of Multilayered TiN/CrN Coatings at Micro- and Nano-length Scales, Thin Solid Films, 2014, 571(2), p 308-31

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE-Glycated hemoglobin (HbA(1c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA(1c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA(1c) levels.RESEARCH DESIGN AND METHODS-We studied associations with HbA(1c) in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA(1c) loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening.RESULTS-Ten loci reached genome-wide significant association with HbA(1c), including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 x 10(-26)), HFE (rs1800562/P = 2.6 x 10(-20)), TMPRSS6 (rs855791/P = 2.7 x 10(-14)), ANK1 (rs4737009/P = 6.1 x 10(-12)), SPTA1 (rs2779116/P = 2.8 x 10(-9)) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 x 10(-9)), and four known HbA(1c) loci: HK1 (rs16926246/P = 3.1 x 10(-54)), MTNR1B (rs1387153/P = 4.0 X 10(-11)), GCK (rs1799884/P = 1.5 x 10(-20)) and G6PC2/ABCB11 (rs552976/P = 8.2 x 10(-18)). We show that associations with HbA(1c) are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (%HbA(1c)) difference between the extreme 10% tails of the risk score, and would reclassify similar to 2% of a general white population screened for diabetes with HbA(1c).CONCLUSIONS-GWAS identified 10 genetic loci reproducibly associated with HbA(1c). Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA(1c) levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA(1c) Diabetes 59: 3229-3239, 201

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389

Recapitulation of Fibromatosis Nodule by Multipotential Stem Cells in Immunodeficient Mice

Musculoskeletal fibromatosis remains a disease of unknown etiology. Surgical excision is the standard of care, but the recurrence rate remains high. Superficial fibromatosis typically presents as subcutaneous nodules caused by rapid myofibroblast proliferation followed by slow involution to dense acellular fibrosis. In this study, we demonstrate that fibromatosis stem cells (FSCs) can be isolated from palmar nodules but not from cord or normal palm tissues. We found that FSCs express surface markers such as CD29, CD44, CD73, CD90, CD105, and CD166 but do not express CD34, CD45, or CD133. We also found that FSCs are capable of expanding up to 20 passages, that these cells include myofibroblasts, osteoblasts, adipocytes, chondrocytes, hepatocytes, and neural cells, and that these cells possess multipotentiality to develop into the three germ layer cells. When implanted beneath the dorsal skin of nude mice, FSCs recapitulated human fibromatosis nodules. Two weeks after implantation, the cells expressed immunodiagnostic markers for myofibroblasts such as α-smooth muscle actin and type III collagen. Two months after implantation, there were fewer myofibroblasts and type I collagen became evident. Treatment with the antifibrogenic compound Trichostatin A (TSA) inhibited the proliferation and differentiation of FSCs in vitro. Treatment with TSA before or after implantation blocked formation of fibromatosis nodules. These results suggest that FSCs are the cellular origin of fibromatosis and that these cells may provide a promising model for developing new therapeutic interventions