On the shortest distance between orbits and the longest common substring problem

In this paper, we study the behaviour of the shortest distance between orbits and show that under some rapidly mixing conditions, the decay of the shortest distance depends on the correlation dimension. For irrational rotations, we prove a different behaviour depending on the irrational exponent of the angle of the rotation. For random processes, this problem corresponds to the longest common substring problem. We extend the result of Arratia and Waterman on sequence matching to $\alpha$-mixing processes with exponential decay.Comment: Final version. Accepted for publication in Advances in Mathematic

Lilith : une androgynie oubliée

Qui est donc Lilith, cette figure féminine qui dans la tradition juive est réputée avoir été la première compagne d’Adam ? En partie oubliée par l’histoire et les textes d’exégèses issus de la chrétienté, Lilith prit une place sporadique et trouble dans les différents systèmes de croyances judéo-chrétiens portés sur la Femme et sa sexualité. Cette démone est au carrefour de plusieurs religions et demeure, semble t-il, la figure féminine qui témoigne le plus universellement des craintes, préjugés et désirs portés sur la Femme et ses mystères supposés. On la retrouve au centre de plusieurs mythes hérités de populations diverses, ce qui pourrait témoigner d’une structure unitaire du penser humain concernant le féminin. Les récits hébraïques et juifs la présentèrent sous l’aspect d’une démone aux attributs masculins et dévorateurs. Malgré cette présence dans la littérature juive, on ne la trouve guère présente dans les écrits de la chrétienté antérieurs au XVIe siècle, si ce n’est dans un texte de saint Augustin qui la déclare être une illusion de l’esprit. Les versions de la Bible et conceptions chrétiennes ne gardèrent pour figure centrale du mythe de la création qu’une seule femme : l’Ève que nous connaissons. Selon les croyances, Lilith fut remplacée par cette femme plus sage. Il faut attendre la Renaissance pour trouver le nom de Lilith dans les écrits chrétiens. Son caractère androgyne la place au centre de tous les mythes qui traitent de la sexualité, de l’amour, de la distinction des sexes, de la question des origines, du pouvoir et de la force la plus obscure de l’humain : son animalité.Who is Lilith, this feminine figure who, according to Jewish tradition, is supposed to have been Adam’s first companion ? More or less forgotten by history and Christian exegetical texts, Lilith holds a sporadic and somewhat vague position in the various Judeo-Christian belief systems related to women and feminine sexuality. This demon is at the crossroads of several religions and seems to be the feminine figure that most universally represents the fears, prejudices and desires directed towards women and their supposed mysteries. She appears at the center of several myths that have come down from populations as diverse as they are distinct, which could suggest a certain universalism in the structure of human thought concerning the feminine. Lilith came into existence in the form of Hebraic and Jewish accounts, being presented in Talmudic and Midrashic literatures as a devouring female demon with masculine traits. Despite this presence in Jewish literature, she is barely present in Christian writings before the 16th century, with one notable exception in a text by Saint Augustine, who declares her to be an illusion of the mind. The various versions of the Bible and Christian conceptions retained only one woman in the central myth of the creation: Eve. According to some beliefs, Lilith was replaced by this more wellbehaved woman. It is not until the Renaissance that one finds the name Lilith in Christian writings. Lilith’s androgynous character places her at the center of all myths that deal with sexuality, love, the distinction between the sexes, the question of origins, power and the most obscure force in humanity: its animal nature.Quien es Lilith, esta figura femenina que en la tradición judía es supuestamente la primera compañera de Adán ? En parte olvidada por la historia y los textos de exégesis originarios de la cristiandad, Lilith toma un lugar esporádico y poco claro en los diferentes sistemas de creencias judeo-cristianas sobre la Mujer y su sexualidad. Este demonio está en la encrucijada de varias religiones, y permanece aparentemente como la figura femenina que testimonia el más universal de los temores, prejuicios y deseos sobre la Mujer y sus supuestos misterios. Se la encuentra en el centro de muchos mitos heredados de poblaciones diversas, lo que podría testimoniar la existencia de una estructura unitaria del pensamiento humano relativo a lo femenino. Los relatos hebraicos y judíos, la presentan bajo el aspecto de un demonio de atributos masculinos y devoradores en las literaturas talmúdicas y midráquicas. Aunque presente en la literatura judía, no se la encuentra presente en los escritos de la cristiandad anteriores al siglo XVI, excepto en un texto de San Agustín, que la declara una ilusión del espíritu. Las versiones de la Biblia y las concepciones cristianas conservaron como figura central del mito de la creación a una sola mujer: la Eva que nosotros conocemos. Según las creencias, Lilith fue reemplazada por esta mujer más prudente. Hay que esperar al Renacimiento para encontrar el nombre de Lilith en los escritos cristianos. Su carácter andrógino la ubica en el centro de todos los mitos que tratan sobre la sexualidad, el amor, la distinción de los sexos, la cuestión de los orígenes, del poder y de la fuerza más oscura del ser humano: su animalidad

Common Threads: An Integrated HIV Prevention and Vocational Development Intervention for African American Women Living with HIV/AIDS

Current policies and initiatives call for the integration of social determinants of health into HIV/AIDS prevention and care interventions. According to the World Health Organization’s Commission on Social Determinants of Health, the lower a person’s socioeconomic status, the worse the health outcomes. One way to alleviate poverty among African American women with HIV/AIDS is to help foster their vocational development and economic empowerment. The National HIV/AIDS Strategy Implementation Plan specifically directs federal agencies to find ways to integrate people living with HIV/AIDS into broader employment initiatives. The purpose of this manuscript is to examine medical, psychosocial, financial/legal and vocational social determinants of health through the lens of the Client-Focused Considering Work Model (Goldblum and Kohlenberg, 2005). The authors then apply this model to the development of a culturally sensitive, integrated HIV prevention and vocational development intervention: Common Threads

Nacre, a natural, multi-use, and timely biomaterial for bone graft substitution

International audienceDuring the past two decades, with a huge and rapidly increasing clinical need for bone regeneration and repair, bone substitutes are more and more seen as a potential solution. Major innovation efforts are being made to develop such substitutes , some having advanced even to clinical practice. It is now time to turn to natural biomaterials. Nacre, or mother-of-pearl, is an organic matrix-calcium carbonate coupled shell structure produced by molluscs. In vivo and in vitro studies have revealed that nacre is osteoinductive, osteoconductive, biocompatible, and biodegradable. With many other outstanding qualities, nacre represents a natural and multi-use biomaterial as a bone graft substitute. This review aims at summarising the current needs in orthopaedic clinics and the challenges for the development of bone substitutes; most of all, we systematically review the physiological characteristics and biological evidence of nacre's effects centred on osteogen-esis, and finally we put forward the potential use of nacre as a bone graft substitute

Serum Markers of Hepatocyte Death and Apoptosis Are Non Invasive Biomarkers of Severe Fibrosis in Patients with Alcoholic Liver Disease

BACKGROUND: Quantification of hepatocyte death is useful to evaluate the progression of alcoholic liver diseases. Our aims were to quantify and correlate the circulating levels of Cytokeratin 18 (CK18) and its caspases-generated fragment to disease severity in heavy alcoholics. METHODOLOGY/PRINCIPAL FINDINGS: CK18 and CK18-fragment were evaluated in the serum of 143 heavy alcoholics. Serum levels of markers of hepatocyte death (CK18), apoptosis (CK18 fragment) and necrosis (CK18 -CK18 fragment) increased in patients with severe fibrosis compared to patients with mild fibrosis. These markers strongly correlated with Mallory-Denk bodies, hepatocyte ballooning, fibrosis and with hepatic TNFα and TGFβ assessed in the liver of 24 patients. Elevated levels of serum hepatocyte death and apoptotic markers were independent risk factors in predicting severe fibrosis in a model combining alkaline phosphatase, bilirubin, prothrombin index, hyaluronate, hepatocyte death and apoptotic markers. The level of markers of hepatocyte death and apoptosis had an area under the receiving operator curve that predicted severe fibrosis of 0.84 and 0.76, respectively. CONCLUSION/SIGNIFICANCE: Death of hepatocytes can be easily evaluated with serum markers and correlated with severe fibrosis in heavy alcohol drinkers. These biomarkers could be useful to rapidly evaluate liver injuries and the efficacy of therapies

Identification of a novel CHEK2 variant and assessment of its contribution to the risk of breast cancer in French Canadian women

<p>Abstract</p> <p>Background</p> <p><it>BRCA1 </it>and <it>BRCA2 </it>account for the majority of the known familial breast cancer risk, however, the impact of other cancer susceptibility genes largely remains to be elucidated. Checkpoint Kinase 2 (<it>CHEK2</it>) is an important signal transducer of cellular responses to DNA damage, whose defects have been associated with an increase in breast cancer risk. Previous studies have identified low penetrance <it>CHEK2 </it>alleles such as 1100delC and I157T, as well as variants such as S428F in the Ashkenazi Jewish population and IVS2 + 1G>A in the Polish population. No founder allele has been specifically identified in the French Canadian population.</p> <p>Methods</p> <p>The 14 coding exons of <it>CHEK2 </it>were fully sequenced for variant alleles in a panel of 25 affected French Canadian women and 25 healthy controls. Two variants were identified of which one novel variant was further screened for in an additional panel of 667 breast cancer patients and 6548 healthy controls. Additional genotyping was conducted using allele specific PCR and a restriction digest assay. Significance of amino acid substitutions were deduced by employing comparative analysis techniques.</p> <p>Results</p> <p>Two variants were identified: the previously reported silent substitution 252A>G (E84E) and the novel missense variant, 1217G>A (R406H). No significant difference in allele distribution between French Canadian women with breast cancer and healthy controls was observed (3/692, 0.43% vs. 22/6573, 0.33%, respectively, P = 0.73).</p> <p>Conclusion</p> <p>The novel CHEK2 missense variant identified in this study, R406H, is unlikely to contribute to breast cancer risk in French Canadian women.</p

Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer

The success of anticancer chemotherapy relies at least in part on the induction of an immune response against tumor cells. Thus, tumors growing on mice that lack the pattern recognition receptor TLR4 or the purinergic receptor P2RX7 fail to respond to chemotherapy with anthracyclins or oxaliplatin in conditions in which the same neoplasms growing on immunocompetent mice would do so. Similarly, the therapeutic efficacy (measured as progression-free survival) of adjuvant chemotherapy with anthracyclins is reduced in breast cancer patients bearing loss-of-function alleles of TLR4 or P2RX7. TLR4 loss-of-function alleles also have a negative impact on the therapeutic outcome of oxaliplatin in colorectal cancer patients. Here, we report that loss-of-function TLR4 and P2RX7 alleles do not affect overall survival in non-small cell lung cancer (NSCLC) patients, irrespective of the administration and type of chemotherapy. The intrinsic characteristics of NSCLC (which near-to-always is chemoresistant and associated with poor prognosis) and/or the type of therapy that is employed to treat this malignancy (which near-to-always is based on cisplatin) may explain why two genes that affect the immune response to dying cells fail to influence the clinical progression of NSCLC patients

Constitutional mismatch repair deficiency–associated brain tumors: report from the European C4CMMRD consortium

Abstract Background Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment. Methods Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017. Results Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1–40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19–45) and 22% (95% CI: 12–37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families). Conclusions Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches

Arsenic Triglutathione [As(GS) 3 ] Transport by Multidrug Resistance Protein 1 (MRP1/ABCC1) Is Selectively Modified by Phosphorylation of Tyr920/Ser921 and Glycosylation of Asn19/Asn23

ABSTRACT The ATP-binding cassette (ABC) transporter multidrug resistance protein 1 (MRP1/ABCC1) is responsible for the cellular export of a chemically diverse array of xenobiotics and endogenous compounds. Arsenic, a human carcinogen, is a high-affinity MRP1 substrate as arsenic triglutathione [As(GS) 3 ]. In this study, marked differences in As(GS) 3 transport kinetics were observed between MRP1-enriched membrane vesicles prepared from human embryonic kidney 293 (HEK) (K m 3.8 mM and V max 307 pmol/mg per minute) and HeLa (K m 0.32 mM and V max 42 pmol/mg per minute) cells. Mutant MRP1 lacking N-linked glycosylation [Asn19/23/1006Gln; sugar-free (SF)-MRP1] expressed in either HEK293 or HeLa cells had low K m and V max values for As(GS) 3 , similar to HeLa wild-type (WT) MRP1. When prepared in the presence of phosphatase inhibitors, both WT-and SF-MRP1-enriched membrane vesicles had a high K m value for As(GS) 3 (3-6 mM), regardless of the cell line. Kinetic parameters of As(GS) 3 for HEKAsn19/23Gln-MRP1 were similar to those of HeLa/HEK-SF-MRP1 and HeLa-WT-MRP1, whereas those of single glycosylation mutants were like those of HEK-WT-MRP1. Mutation of 19 potential MRP1 phosphorylation sites revealed that HEK-Tyr920Phe/ Ser921Ala-MRP1 transported As(GS) 3 like HeLa-WT-MRP1, whereas individual HEK-Tyr920Phe-and -Ser921Ala-MRP1 mutants were similar to HEK-WT-MRP1. Together, these results suggest that Asn19/Asn23 glycosylation and Tyr920/Ser921 phosphorylation are responsible for altering the kinetics of MRP1-mediated As(GS) 3 transport. The kinetics of As(GS) 3 transport by HEK-Asn19/23Gln/Tyr920Glu/Ser921Glu were similar to HEK-WT-MRP1, indicating that the phosphorylation-mimicking substitutions abrogated the influence of Asn19/23Gln glycosylation. Overall, these data suggest that cross-talk between MRP1 glycosylation and phosphorylation occurs and that phosphorylation of Tyr920 and Ser921 can switch MRP1 to a lower-affinity, higher-capacity As(GS) 3 transporter, allowing arsenic detoxification over a broad concentration range