Multiscaling in passive scalar advection as stochastic shape dynamics

The Kraichnan rapid advection model is recast as the stochastic dynamics of tracer trajectories. This framework replaces the random fields with a small set of stochastic ordinary differential equations. Multiscaling of correlation functions arises naturally as a consequence of the geometry described by the evolution of N trajectories. Scaling exponents and scaling structures are interpreted as excited states of the evolution operator. The trajectories become nearly deterministic in high dimensions allowing for perturbation theory in this limit. We calculate perturbatively the anomalous exponent of the third and fourth order correlation functions. The fourth order result agrees with previous calculations.Comment: 14 pages, LaTe

The activation of the atypical PKC zeta in light-induced retinal degeneration and its involvement in L-DNase II control.

Light-induced retinal degeneration is characterized by photoreceptor cell death. Many studies showed that photoreceptor demise is caspase-independent. In our laboratory we showed that leucocyte elastase inhibitor/LEI-derived DNase II (LEI/L-DNase II), a caspase-independent apoptotic pathway, is responsible for photoreceptor death. In this work, we investigated the activation of a pro-survival kinase, the protein kinase C (PKC) zeta. We show that light exposure induced PKC zeta activation. PKC zeta interacts with LEI/L-DNase II and controls its DNase activity by impairing its nuclear translocation. These results highlight the role of PKC zeta in retinal physiology and show that this kinase can control caspase-independent pathways

Anomalous Scaling in a Model of Passive Scalar Advection: Exact Results

Kraichnan's model of passive scalar advection in which the driving velocity field has fast temporal decorrelation is studied as a case model for understanding the appearance of anomalous scaling in turbulent systems. We demonstrate how the techniques of renormalized perturbation theory lead (after exact resummations) to equations for the statistical quantities that reveal also non perturbative effects. It is shown that ultraviolet divergences in the diagrammatic expansion translate into anomalous scaling with the inner length acting as the renormalization scale. In this paper we compute analytically the infinite set of anomalous exponents that stem from the ultraviolet divergences. Notwithstanding, non-perturbative effects furnish a possibility of anomalous scaling based on the outer renormalization scale. The mechanism for this intricate behavior is examined and explained in detail. We show that in the language of L'vov, Procaccia and Fairhall [Phys. Rev. E {\bf 50}, 4684 (1994)] the problem is ``critical" i.e. the anomalous exponent of the scalar primary field $\Delta=\Delta_c$. This is precisely the condition that allows for anomalous scaling in the structure functions as well, and we prove that this anomaly must be based on the outer renormalization scale. Finally, we derive the scaling laws that were proposed by Kraichnan for this problem, and show that his scaling exponents are consistent with our theory.Comment: 43 pages, revtex

Les lymphomes de l’anneau de Waldeyer traitement et pronostic

Les lymphomes non Hodgkiniens (LNH) qui prennent naissance au niveau de l’anneau de Waldeyer constituent une entité bien particulière tant sur le plan clinique, thérapeutique que pronostique. Les auteurs rapportent une étude rétrospective de 44 observations de LNH de l’anneau de Waldeyer colligées entre 1995 et 2002. Une chimiothérapie exclusive aété indiquée chez 80,6% des malades et une association chimio-radiothérapie a été réalisée chez 19,4%. Le taux de survie globale était de 42% à 5 ans. Dans notre étude quatre facteurs de mauvais pronostic ont été individualisés : un âge ≥ à 40 ans, les stades d’Ann Arbor II, III et IV, un taux de LDH ≥ 1,5 fois la normale et la survenue de rechute.Mots-clés : Lymphome, anneau de Waldeyer, chimiothérapie, radiothérapie, pronosti

Exploring the functional interaction between POSH and ALIX and the relevance to HIV-1 release

<p>Abstract</p> <p>Background</p> <p>The ALG2-interacting protein X (ALIX)/AIP1 is an adaptor protein with multiple functions in intracellular protein trafficking that plays a central role in the biogenesis of enveloped viruses. The ubiquitin E3-ligase POSH (plenty of SH3) augments HIV-1 egress by facilitating the transport of Gag to the cell membrane. Recently, it was reported, that POSH interacts with ALIX and thereby enhances ALIX mediated phenotypes in <it>Drosophila</it>.</p> <p>Results</p> <p>In this study we identified ALIX as a POSH ubiquitination substrate in human cells: POSH induces the ubiquitination of ALIX that is modified on several lysine residues <it>in vivo </it>and <it>in vitro</it>. This ubiquitination does not destabilize ALIX, suggesting a regulatory function. As it is well established that ALIX rescues virus release of L-domain mutant HIV-1, HIV-1Δ_PTAP, we demonstrated that wild type POSH, but not an ubiquitination inactive RING finger mutant (POSH^V14A), substantially enhances ALIX-mediated release of infectious virions derived from HIV-1Δ_PTAPL-domain mutant (YPX_nL-dependent HIV-1). In further agreement with the idea of a cooperative function of POSH and ALIX, mutating the YPX_nL-ALIX binding site in Gag completely abrogated augmentation of virus release by overexpression of POSH. However, the effect of the POSH-mediated ubiquitination appears to be auxiliary, but not necessary, as silencing of POSH by RNAi does not disturb ALIX-augmentation of virus release.</p> <p>Conclusion</p> <p>Thus, the cumulative results identified ALIX as an ubiquitination substrate of POSH and indicate that POSH and ALIX cooperate to facilitate efficient virus release. However, while ALIX is obligatory for the release of YPX_nL-dependent HIV-1, POSH, albeit rate-limiting, may be functionally interchangeable.</p

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling.

Sanguinarine (SNG), a benzophenanthridine alkaloid, has displayed various anticancer abilities in several vivo and studies. However, the anticancer potential of SNG is yet to be established in multiple myeloma (MM), a mostly incurable malignancy of plasma cells. In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppression of the constitutively active STAT3 with a concomitant increase in expression of protein tyrosine phosphatase (SHP-1). SNG treatment of MM cells leads to down-regulation of the anti-apoptotic proteins including cyclin D, Bcl-2, Bclxl, and XIAP. In addition, it also upregulates pro-apoptotic protein, Bax. SNG mediated cellular DNA damage in MM cell lines by induction of oxidative stress through the generation of reactive oxygen species and depletion of glutathione. Finally, the subtoxic concentration of SNG enhanced the cytotoxic effects of anticancer drugs bortezomib (BTZ) by suppressing the viability of MM cells via induction of caspase-mediated apoptosis. Altogether our findings demonstrate that SNG induces mitochondrial and caspase-dependent apoptosis, generates oxidative stress, and suppresses MM cell lines proliferation. In addition, co-treatment of MM cell lines with sub-toxic doses of SNG and BTZ potentiated the cytotoxic activity. These results would suggest that SNG could be developed into therapeutic agent either alone or in combination with other anticancer drugs in MM

Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects and tissue-specific enrichment of eQTLs

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci

Common Sense Recommendations for the Application of Tax Law to Digital Assets

In response to the Joint Committee on Taxation’s July 2023 request for comments on application of various Internal Revenue Code sections on digital assets, we propose a consistent set of rules to apply current law to digital assets. We highlight that the underlying economics and characteristics of transactions should be the primary concern for the application of rules and the valuation of digital assets. We believe any digital asset rules should (1) treat classes of digital assets with unique characteristics differently based on their economics, (2) minimize incentives for users to engage in tax-motivated structuring of transactions, and (3) allow the Internal Revenue Service authority to react to and regulate new classes of digital assets as they are created. We do not believe that the unique features of digital assets are a challenge to applying current law or warrant special tax preferred treatment

Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition

Antibodies targeting citrullinated proteins (ACPAs [anticitrullinated protein antibodies]) are commonly found in patients with rheumatoid arthritis (RA), strongly associate with distinct HLA-DR alleles, and predict a more aggressive disease course as compared with seronegative patients. Still, many features of these antibodies, including their site of production and the extent of MHC class II–driven T cell help, remain unclarified. To address these questions, we have used a single B cell–based cloning technology to isolate and express immunoglobulin (Ig) genes from joint-derived B cells of active RA patients. We found ∼25% of synovial IgG-expressing B cells to be specific for citrullinated autoantigens in the investigated ACPA+ RA patients, whereas such antibodies were not found in ACPA− patients. The citrulline-reactive monoclonal antibodies did not react with the unmodified arginine peptides, yet several reacted with more than one citrullinated antigen. A role for active antigen selection of the citrulline-reactive synovial B cells was supported by the strong bias toward amino acid replacement mutations in ACPA+ antibodies and by their loss of reactivity to citrullinated autoantigens when somatic mutations were reverted to the corresponding germline sequences

Molecular study of the perforin gene in familial hematological malignancies

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein