Longitude : a privacy-preserving location sharing protocol for mobile applications

Location sharing services are becoming increasingly popular. Although many location sharing services allow users to set up privacy policies to control who can access their location, the use made by service providers remains a source of concern. Ideally, location sharing providers and middleware should not be able to access users’ location data without their consent. In this paper, we propose a new location sharing protocol called Longitude that eases privacy concerns by making it possible to share a user’s location data blindly and allowing the user to control who can access her location, when and to what degree of precision. The underlying cryptographic algorithms are designed for GPS-enabled mobile phones. We describe and evaluate our implementation for the Nexus One Android mobile phone

On the nature of tunable hole g-factors in quantum dots

Electrically tunable g-factors in quantum dots are highly desirable for applications in quantum computing and spintronics. We report giant modulation of the hole g-factor in a SiGe nanocrystal when an electric field is applied to the nanocrystal along its growth direction. We derive a contribution to the g-factor that stems from an orbital effect of the magnetic field, which lifts the Kramers degeneracy in the nanocrystal by altering the mixing between the heavy and the light holes. We show that the relative displacement between the heavy- and light-hole wave functions, occurring upon application of the electric field, has an effect on the mixing strength and leads to a strong non-monotonic modulation of the g-factor. Despite intensive studies of the g-factor since the late 50's, this mechanism of g-factor control has been largely overlooked in the literature.Comment: 9 pages, 6 figure

Observation of spin-selective tunneling in SiGe nanocrystals

Spin-selective tunneling of holes in SiGe nanocrystals contacted by normal-metal leads is reported. The spin selectivity arises from an interplay of the orbital effect of the magnetic field with the strong spin-orbit interaction present in the valence band of the semiconductor. We demonstrate both experimentally and theoretically that spin-selective tunneling in semiconductor nanostructures can be achieved without the use of ferromagnetic contacts. The reported effect, which relies on mixing the light and heavy holes, should be observable in a broad class of quantum-dot systems formed in semiconductors with a degenerate valence band.Comment: 8 pages, 5 figure

The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

International audienceHeparan sulfate (HS) proteoglycan chains are key components of the breast tumor microenvironment that critically influence the behavior of cancer cells. It is established that abnormal synthesis and processing of HS play a prominent role in tumorigenesis, albeit mechanisms remain mostly obscure. HS function is mainly controlled by sulfotransferases, and here we report a novel cellular and pathophysiological significance for the 3-O-sulfotransferase 3-OST3A (HS3ST3A), catalyzing the final maturation step of HS, in breast cancer. We show that 3-OST3A is epigenetically repressed in all breast cancer cell lines of a panel representative of distinct molecular subgroups, except in human epidermal growth factor receptor 2-positive (HER2+) sloan-kettering breast cancer (SKBR3) cells. Epigenetic mechanisms involved both DNA methylation and histone modifications, producing different repressive chromatin environments depending on the cell molecular signature. Gain and loss of function experiments by cDNA and siRNA transfection revealed profound effects of 3-OST3A expression on cell behavior including apoptosis, proliferation, response to trastuzumab in vitro and tumor growth in xenografted mice. 3-OST3A exerted dual activities acting as tumor-suppressor in lumA-michigan cancer foundation (MCF)-7 and triple negative-MD Anderson (MDA) metastatic breast (MB)-231 cells, or as an oncogenic factor in HER2+-SKBR3 cells. Mechanistically, fluorescence-resonance energy transfer-fluorescence-lifetime imaging microscopy experiments indicated that the effects of 3-OST3A in MCF-7 cells were mediated by altered interactions between HS and fibroblast growth factor-7 (FGF-7). Further, this interplay between HS and FGF-7 modulated downstream ERK, AKT and p38 cascades, suggesting that altering 3-O-sulfation affects FGFR2IIIb-mediated signaling. Corroborating our cellular data, a clinical study conducted in a cohort of breast cancer patients uncovered that, in HER2+ patients, high level expression of 3-OST3A in tumors was associated with reduced relapse-free survival. Our findings define 3-OST3A as a novel regulator of breast cancer pathogenicity, displaying tumor-suppressive or oncogenic activities in a cell-and tumor-dependent context, and demonstrate the clinical value of the HS-O-sulfotransferase 3-OST3A as a prognostic marker in HER2+ patients

HERALD (Health Economics using Routine Anonymised Linked Data)

<b>Background</b> Health economic analysis traditionally relies on patient derived questionnaire data, routine datasets, and outcomes data from experimental randomised control trials and other clinical studies, which are generally used as stand-alone datasets. Herein, we outline the potential implications of linking these datasets to give one single joined up data-resource for health economic analysis.<p></p> <b>Method</b> The linkage of individual level data from questionnaires with routinely-captured health care data allows the entire patient journey to be mapped both retrospectively and prospectively. We illustrate this with examples from an Ankylosing Spondylitis (AS) cohort by linking patient reported study dataset with the routinely collected general practitioner (GP) data, inpatient (IP) and outpatient (OP) datasets, and Accident and Emergency department data in Wales. The linked data system allows: (1) retrospective and prospective tracking of patient pathways through multiple healthcare facilities; (2) validation and clarification of patient-reported recall data, complementing the questionnaire/routine data information; (3) obtaining objective measure of the costs of chronic conditions for a longer time horizon, and during the pre-diagnosis period; (4) assessment of health service usage, referral histories, prescribed drugs and co-morbidities; and (5) profiling and stratification of patients relating to disease manifestation, lifestyles, co-morbidities, and associated costs.<p></p> <b>Results</b> Using the GP data system we tracked about 183 AS patients retrospectively and prospectively from the date of questionnaire completion to gather the following information: (a) number of GP events; (b) presence of a GP 'drug' read codes; and (c) the presence of a GP 'diagnostic' read codes. We tracked 236 and 296 AS patients through the OP and IP data systems respectively to count the number of OP visits; and IP admissions and duration. The results are presented under several patient stratification schemes based on disease severity, functions, age, sex, and the onset of disease symptoms.<p></p> <b>Conclusion</b> The linked data system offers unique opportunities for enhanced longitudinal health economic analysis not possible through the use of traditional isolated datasets. Additionally, this data linkage provides important information to improve diagnostic and referral pathways, and thus helps maximise clinical efficiency and efficiency in the use of resources

The role of HLA-G in human pregnancy

Pregnancy in mammals featuring hemochorial placentation introduces a major conflict with the mother's immune system, which is dedicated to repelling invaders bearing foreign DNA and RNA. Numerous and highly sophisticated strategies for preventing mothers from rejecting their genetically different fetus(es) have now been identified. These involve production of novel soluble and membrane-bound molecules by uterine and placental cells. In humans, the placenta-derived molecules include glycoproteins derived from the HLA class Ib gene, HLA-G. Isoforms of HLA-G saturate the maternal-fetal interface and circulate in mothers throughout pregnancy. Uteroplacental immune privilege for the fetus and its associated tissues is believed to result when immune cells encounter HLA-G. Unequivocally demonstration of this concept requires experiments in animal models. Both the monkey and the baboon express molecules that are similar but not identical to HLA-G, and may comprise suitable animal models for establishing a central role for these proteins in pregnancy

High Level of Soluble HLA-G in the Female Genital Tract of Beninese Commercial Sex Workers Is Associated with HIV-1 Infection

Most HIV infections are transmitted across mucosal epithelium. Understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, are of fundamental importance. HLA-G is a powerful modulator of the immune response. The aim of this study was to investigate whether soluble HLA-G (sHLA-G) expression in the female genital tract is associated with HIV-1 infection.Genital levels of sHLA-G were determined in 52 HIV-1-uninfected and 44 antiretroviral naïve HIV-1-infected female commercial sex workers (CSWs), as well as 71 HIV-1-uninfected non-CSW women at low risk of exposure, recruited in Cotonou, Benin. HIV-1-infected CSWs had higher genital levels of sHLA-G compared with those in both the HIV-1-uninfected CSW (P = 0.009) and non-CSW groups (P = 0.0006). The presence of bacterial vaginosis (P = 0.008), and HLA-G*01:01:02 genotype (P = 0.002) were associated with higher genital levels of sHLA-G in the HIV-1-infected CSWs, whereas the HLA-G*01:04:04 genotype was also associated with higher genital level of sHLA-G in the overall population (P = 0.038). When adjustment was made for all significant variables, the increased expression of sHLA-G in the genital mucosa remained significantly associated with both HIV-1 infection (P = 0.02) and bacterial vaginosis (P = 0.03).This study demonstrates that high level of sHLA-G in the genital mucosa is independently associated with both HIV-1 infection and bacterial vaginosis

Histone deacetylase inhibitors in Hodgkin lymphoma

Although Hodgkin lymphoma (HL) is considered one of the most curable human cancers, the treatment of patients with relapsed and refractory disease, especially those who relapse after autologous stem cell transplantation, remains challenging. Furthermore, because of the young age of these patients, the impact of early mortality on the number of years lost from productive life is remarkable. Patients with relapsed HL post stem cell transplantation currently have no curative therapy, and are in need for new drugs and novel treatment strategies. While no new drugs have been approved for the treatment of patients with HL in more than three decades, several new agents are demonstrating promising results in early clinical trials. This review will focus on the emerging role of histone deacetylase inhibitors in patients with relapsed HL

The histone deacetylase inhibitor Trichostatin A modulates CD4+ T cell responses

BACKGROUND: Histone deacetylase inhibitors (HDACIs) induce hyperacetylation of core histones modulating chromatin structure and affecting gene expression. These compounds are also able to induce growth arrest, cell differentiation, and apoptotic cell death of tumor cells in vitro as well as in vivo. Even though several genes modulated by HDAC inhibition have been identified, those genes clearly responsible for the biological effects of these drugs have remained elusive. We investigated the pharmacological effect of the HDACI and potential anti-cancer agent Trichostatin A (TSA) on primary T cells. METHODS: To ascertain the effect of TSA on resting and activated T cells we used a model system where an enriched cell population consisting of primary T-cells was stimulated in vitro with immobilized anti-CD3/anti-CD28 antibodies whilst exposed to pharmacological concentrations of Trichostatin A. RESULTS: We found that this drug causes a rapid decline in cytokine expression, accumulation of cells in the G(1 )phase of the cell cycle, and induces apoptotic cell death. The mitochondrial respiratory chain (MRC) plays a critical role in the apoptotic response to TSA, as dissipation of mitochondrial membrane potential and reactive oxygen species (ROS) scavengers block TSA-induced T-cell death. Treatment of T cells with TSA results in the altered expression of a subset of genes involved in T cell responses, as assessed by microarray gene expression profiling. We also observed up- as well as down-regulation of various costimulatory/adhesion molecules, such as CD28 and CD154, important for T-cell function. CONCLUSIONS: Taken together, our findings indicate that HDAC inhibitors have an immunomodulatory potential that may contribute to the potency and specificity of these antineoplastic compounds and might be useful in the treatment of autoimmune disorders

Characterization of a Nonclassical Class I MHC Gene in a Reptile, the Galápagos Marine Iguana (Amblyrhynchus cristatus)

Squamates are a diverse order of vertebrates, representing more than 7,000 species. Yet, descriptions of full-length major histocompatibility complex (MHC) genes in this group are nearly absent from the literature, while the number of MHC studies continues to rise in other vertebrate taxa. The lack of basic information about MHC organization in squamates inhibits investigation into the relationship between MHC polymorphism and disease, and leaves a large taxonomic gap in our understanding of amniote MHC evolution. Here, we use both cDNA and genomic sequence data to characterize a class I MHC gene (Amcr-UA) from the Galápagos marine iguana, a member of the squamate subfamily Iguaninae. Amcr-UA appears to be functional since it is expressed in the blood and contains many of the conserved peptide-binding residues that are found in classical class I genes of other vertebrates. In addition, comparison of Amcr-UA to homologous sequences from other iguanine species shows that the antigen-binding portion of this gene is under purifying selection, rather than balancing selection, and therefore may have a conserved function. A striking feature of Amcr-UA is that both the cDNA and genomic sequences lack the transmembrane and cytoplasmic domains that are necessary to anchor the class I receptor molecule into the cell membrane, suggesting that the product of this gene is secreted and consequently not involved in classical class I antigen-presentation. The truncated and conserved character of Amcr-UA lead us to define it as a nonclassical gene that is related to the few available squamate class I sequences. However, phylogenetic analysis placed Amcr-UA in a basal position relative to other published classical MHC genes from squamates, suggesting that this gene diverged near the beginning of squamate diversification