KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection

Funding Information: This research was supported in part by Cancer Research Switzerland , Switzerland ( KFS-4091-02-2017 ); KFSP-PrecisionMS and HMZ ImmunoTargET of the University of Zurich , Switzerland; the Cancer Research Center Zurich , Switzerland; the Vontobel Foundation , Switzerland; the Baugarten Foundation , Switzerland; the Sobek Foundation , Germany; the Swiss Vaccine Research Institute , Switzerland; Roche , Switzerland; Novartis , Switzerland; and the Swiss National Science Foundation , Switzerland ( 310030B_182827 and CRSII5_180323 ). A.M.M. was funded by a National Institutes of Health , United States, grant ( R01 CA189806 ). N.C. was supported by a career advancement grant from the University of Zurich , Switzerland ( FK-18-026 ). D.M. and M.B. were supported by MD-PhD fellowships from the Swiss National Science Foundation , Switzerland, and the Swiss Academy of Medical Sciences , Switzerland ( 323530_145247 and 323630_19938 ).Peer reviewedPublisher PD

Rapid intrapartum test for maternal group B streptococcal colonisation and its effect on antibiotic use in labouring women with risk factors for early-onset neonatal infection (GBS2): cluster randomised trial with nested test accuracy study

Background: Mother-to-baby transmission of group B Streptococcus (GBS) is the main cause of early-onset infection. We evaluated whether, in women with clinical risk factors for early neonatal infection, the use of point-of-care rapid intrapartum test to detect maternal GBS colonisation reduces maternal antibiotic exposure compared with usual care, where antibiotics are administered due to those risk factors. We assessed the accuracy of the rapid test in diagnosing maternal GBS colonisation, against the reference standard of selective enrichment culture. Methods: We undertook a parallel-group cluster randomised trial, with nested test accuracy study and microbiological sub-study. UK maternity units were randomised to a strategy of rapid test (GeneXpert GBS system, Cepheid) or usual care. Within units assigned to rapid testing, vaginal-rectal swabs were taken from women with risk factors for vertical GBS transmission in established term labour. The trial primary outcome was the proportion of women receiving intrapartum antibiotics to prevent neonatal early-onset GBS infection. The accuracy of the rapid test was compared against the standard of selective enrichment culture in diagnosing maternal GBS colonisation. Antibiotic resistance profiles were determined in paired maternal and infant samples. Results: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units; 906 mothers (951 babies) were in usual care units. There was no evidence of a difference in the rates of intrapartum antibiotic prophylaxis (relative risk 1.16, 95% CI 0.83 to 1.64) between the rapid test (41%, 297/716) and usual care (36%, 328/906) units. No serious adverse events were reported. The sensitivity and specificity measures of the rapid test were 86% (95% CI 81 to 91%) and 89% (95% CI 85 to 92%), respectively. Babies born to mothers who carried antibiotic-resistant Escherichia coli were more likely to be colonised with antibiotic-resistant strains than those born to mothers with antibiotic-susceptible E. coli. Conclusion: The use of intrapartum rapid test to diagnose maternal GBS colonisation did not reduce the rates of antibiotics administered for preventing neonatal early-onset GBS infection than usual care, although with considerable uncertainty. The accuracy of the rapid test is within acceptable limits. Trial registration: ISRCTN74746075. Prospectively registered on 16 April 2015

International collaborative follow - up investigation of graduating high school students’ understandings of the nature of scientific inquiry: is progress Being made?

Understandings of the nature of scientific inquiry (NOSI), as opposed to engaging students in inquiry learning experiences, are included in science education reform documents around the world. However, little is known about what students have learned about NOSI during their pre-college school years. The purpose of this large-scale follow-up international project (i.e. 32 countries and regions, spanning six continents and including 3917 students for the high school sample) was to collect data on what exiting high school students have learned about NOSI. Additionally, the study investigated changes in 12th grade students’ NOSI understandings compared to seventh grade (i.e. 20 countries and regions) students’ understandings from a prior investigation [Lederman et al. (2019). An international collaborative investigation of beginning seventh grade students’ understandings of scientific inquiry: Establishing a baseline. Journal of Research in Science Teaching, 56(4), 486–515. https://doi.org/10.1002/tea.21512]. This study documents and discusses graduating high school students’ understandings and compares their understandings to seventh grade students’ understandings of the same aspects of scientific inquiry for each country. It is important to note that collecting data from each of the 130+ countries globally was not feasible. Similarly, it was not possible to collect data from every region of each country. A concerted effort was made, however, to provide a relatively representative picture of each country and the world

Persistent KSHV infection increases EBV-associated tumor formation In vivo via enhanced EBV lytic gene expression

The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis. Dual-infected cells displayed a plasma cell-like gene expression pattern similar to PELs. KSHV persisted in EBV-transformed B cells and was associated with lytic EBV gene expression, resulting in increased tumor formation. Evidence of elevated lytic EBV replication was also found in EBV/KSHV dually infected lymphoproliferative disorders in humans. Our data suggest that KSHV augments EBV-associated tumorigenesis via stimulation of lytic EBV replication

Neotectonics of the SW Iberia margin, Gulf of Cadiz and Alboran Sea: a reassessment including recent structural, seismic and geodetic data

We use a thin-shell approximation for the lithosphere to model the neotectonics of the Gulf of Cadiz, SW Iberia margin and the westernmost Mediterranean, in the eastern segment of the Azores-Gibraltar plate boundary. In relation to previous neotectonic models in the region, we utilize a better constrained structural map offshore, and the recent GPS measurements over NW Africa and Iberia have been taken into account, together with the seismic strain rate and stress data, to evaluate alternative geodynamic settings proposed for the region. We show that by assuming a relatively simple, two-plate tectonic framework, where Nubia and Eurasia converge NW-SE to WNW-ESE at a rate of 4.5-6 mm yr-1, the models correctly predict the amount of shortening and wrenching between northern Algeria-Morocco and southern Spain and between NW Morocco and SW Iberia, as estimated from both GPS data and geological constraints. The consistency between modelled and observed velocities in the vicinity of Gibraltar and NW Morocco indicates that forcing by slab sinking beneath Gibraltar is not required to reproduce current horizontal deformation in these areas. In the Gulf of Cadiz and SW Iberia, the modelling results support a diffuse Nubia-Eurasia Plate boundary, where the convergence is accommodated along NNE-SSW to NE-SW and ENE-WSW thrust faults and WNW-ESE right-lateral strike-slip faults, over an area >200 km wide, in good general agreement with the distribution of the seismic strain rate and associated faulting mechanisms. The modelling results are robust to regional uncertainties in the structure of the lithosphere and have important implications for the earthquake and tsunami hazard of Portugal, SW Spain and Morocco. We predict maximum, long-term average fault slip rates between 1-2 mm yr-1, that is, less than 50 per cent the average plate relative movement, suggesting very long return periods for high-magnitude (Mw > 8) earthquakes on individual structures.publishe

Access Control Encryption for General Policies from Standard Assumptions

Functional encryption enables fine-grained access to encrypted data. In many scenarios, however, it is important to control not only what users are allowed to read (as provided by traditional functional encryption), but also what users are allowed to send. Recently, Damgård et al. (TCC 2016) introduced a new cryptographic framework called access control encryption (ACE) for restricting information flow within a system in terms of both what users can read as well as what users can write. While a number of access control encryption schemes exist, they either rely on strong assumptions such as indistinguishability obfuscation or are restricted to simple families of access control policies. In this work, we give the first ACE scheme for arbitrary policies from standard assumptions. Our construction is generic and can be built from the combination of a digital signature scheme, a predicate encryption scheme, and a (single-key) functional encryption scheme that supports randomized functionalities. All of these primitives can be instantiated from standard assumptions in the plain model and therefore, we obtain the first ACE scheme capable of supporting general policies from standard assumptions. One possible instantiation of our construction relies upon standard number-theoretic assumptions (namely, the DDH and RSA assumptions) and standard lattice assumptions (namely, LWE). Finally, we conclude by introducing several extensions to the ACE framework to support dynamic and more fine-grained access control policies

LIGHT/LTβR signaling regulates self-renewal and differentiation of hematopoietic and leukemia stem cells.

The production of blood cells during steady-state and increased demand depends on the regulation of hematopoietic stem cell (HSC) self-renewal and differentiation. Similarly, the balance between self-renewal and differentiation of leukemia stem cells (LSCs) is crucial in the pathogenesis of leukemia. Here, we document that the TNF receptor superfamily member lymphotoxin-β receptor (LTβR) and its ligand LIGHT regulate quiescence and self-renewal of murine and human HSCs and LSCs. Cell-autonomous LIGHT/LTβR signaling on HSCs reduces cell cycling, promotes symmetric cell division and prevents primitive HSCs from exhaustion in serial re-transplantation experiments and genotoxic stress. LTβR deficiency reduces the numbers of LSCs and prolongs survival in a murine chronic myeloid leukemia (CML) model. Similarly, LIGHT/LTβR signaling in human G-CSF mobilized HSCs and human LSCs results in increased colony forming capacity in vitro. Thus, our results define LIGHT/LTβR signaling as an important pathway in the regulation of the self-renewal of HSCs and LSCs

Private search in the real world

Encrypted search — performing queries on protected data — has been explored in the past; however, its inherent inefficiency has raised questions of practicality. Here, we focus on improving the performance and extending its functionality enough to make it practical. We do this by optimizing the system, and by stepping back from the goal of achieving maximal privacy guarantees in an encrypted search scenario and consider efficiency and functionality as priorities. We design and analyze the privacy implications of two prac-tical extensions applicable to any keyword-based private search system. We evaluate their efficiency by building them on top of a private search system, called SADS. Additionally, we im-prove SADS ’ performance, privacy guaranties and functionality. The extended SADS system offers improved efficiency parameters that meet practical usability requirements in a relaxed adversarial model. We present the experimental results and evaluate the per-formance of the system. We also demonstrate analytically that our scheme can meet the basic needs of a major hospital complex’s ad-missions records. Overall, we achieve performance comparable to a simply configured MySQL database system. 1

PAR: Payment for Anonymous Routing

Abstract. Despite the growth of the Internet and the increasing concern for privacy of online communications, current deployments of anonymization networks depend on a very small set of nodes that volunteer their bandwidth. We believe that the main reason is not disbelief in their ability to protect anonymity, but rather the practical limitations in bandwidth and latency that stem from limited participation. This limited participation, in turn, is due to a lack of incentives to participate. We propose providing economic incentives, which historically have worked very well. In this paper, we demonstrate a payment scheme that can be used to compensate nodes which provide anonymity in Tor, an existing onion routing, anonymizing network. We show that current anonymous payment schemes are not suitable and introduce a hybrid payment system based on a combination of the Peppercoin Micropayment system and a new type of “one use ” electronic cash. Our system claims to maintain users ’ anonymity, although payment techniques mentioned previously – when adopted individually – provably fail.