Khazana: a flexible wide area data store

technical reportKhazana is a peer-to-peer data service that supports efficient sharing and aggressive caching of mutable data across the wide area while giving clients significant control over replica divergence. Previous work on wide-area replicated services focussed on at most two of the following three properties: aggressive replication, customizable consistency, and generality. In contrast, Khazana provides scalable support for large numbers of replicas while giving applications considerable flexibility in trading off consistency for availability and performance. Its flexibility enables applications to effectively exploit inherent data locality while meeting consistency needs. Khazana exports a file system-like interface with a small set of consistency controls which can be combined to yield a broad spectrum of consistency flavors ranging from strong consistency to best-effort eventual consistency. Khazana servers form failure-resilient dynamic replica hierarchies to manage replicas across variable quality network links. In this report, we outline Khazana?s design and show how its flexibility enables three diverse network services built on top of it to meet their individual consistency and performance needs: (i) a wide-area replicated file system that supports serializable writes as well as traditional file sharing across wide area, (ii) an enterprise data service that exploits locality by caching enterprise data closer to end-users while ensuring strong consistency for data integrity, and (iii) a replicated database that reaps order of magnitude gains in throughput by relaxing consistency

Flexible consistency for wide area peer replication

technical reportThe lack of a flexible consistency management solution hinders P2P implementation of applications involving updates, such as read-write file sharing, directory services, online auctions and wide area collaboration. Managing mutable shared data in a P2P setting requires a consistency solution that can operate efficiently over variable-quality failure-prone networks, support pervasive replication for scaling, and give peers autonomy to tune consistency to their sharing needs and resource constraints. Existing solutions lack one or more of these features. In this paper, we describe a new consistency model for P2P sharing of mutable data called composable consistency, and outline its implementation in a wide area middleware file service called Swarm1. Composable consistency lets applications compose consistency semantics appropriate for their sharing needs by combining a small set of primitive options. Swarm implements these options efficiently to support scalable, pervasive, failure-resilient, wide-area replication behind a simple yet flexible interface. We present two applications to demonstrate the expressive power and effectiveness of composable consistency: a wide area file system that outperforms Coda in providing close-to-open consistency overWANs, and a replicated BerkeleyDB database that reaps order-of-magnitude performance gains by relaxing consistency for queries and updates

Middleware support for locality-aware wide area replication

technical reportCoherent wide-area data caching can improve the scalability and responsiveness of distributed services such as wide-area file access, database and directory services, and content distribution. However, distributed services differ widely in the frequency of read/write sharing, the amount of contention between clients for the same data, and their ability to make tradeoffs between consistency and availability. Aggressive replication enhances the scalability and availability of services with read-mostly data or data that need not be kept strongly consistent. However, for applications that require strong consistency of writeshared data, you must throttle replication to achieve reasonable performance. We have developed a middleware data store called Swarm designed to support the widearea data sharing needs of distributed services. To support the needs of diverse distributed services, Swarm provides: (i) a failure-resilient proximity-aware data replication mechanism that adjusts the replication hierarchy based on observed network characteristics and node availability, (ii) a customizable consistency mechanism that allows applications to specify allowable consistency-availability tradeoffs, and (iii) a contention-aware caching mechanism that monitors contention between replicas and adjusts its replication policies accordingly. On a 240-node P2P file sharing system, Swarm's proximity-aware caching and replica hierarchy maintenance mechanisms improve latency by 80%, reduce WAN bandwidth consumed by 80%, and limit the impact of high node churn (5 node deaths/sec) to roughly one-fifth that of random replication. In addition, Swarm's contention-aware caching mechanism outperforms RPCs and static caching mechanisms at all levels of contention on an enterprise service workload

High-K dielectric sulfur-selenium alloys.

Upcoming advancements in flexible technology require mechanically compliant dielectric materials. Current dielectrics have either high dielectric constant, K (e.g., metal oxides) or good flexibility (e.g., polymers). Here, we achieve a golden mean of these properties and obtain a lightweight, viscoelastic, high-K dielectric material by combining two nonpolar, brittle constituents, namely, sulfur (S) and selenium (Se). This S-Se alloy retains polymer-like mechanical flexibility along with a dielectric strength (40 kV/mm) and a high dielectric constant (K = 74 at 1 MHz) similar to those of established metal oxides. Our theoretical model suggests that the principal reason is the strong dipole moment generated due to the unique structural orientation between S and Se atoms. The S-Se alloys can bridge the chasm between mechanically soft and high-K dielectric materials toward several flexible device applications

Vitamin D promotes human extravillous trophoblast invasion in vitro

Introduction Incomplete human extravillous trophoblast (EVT) invasion of the decidua and maternal spiral arteries is characteristic of pre-eclampsia, a condition linked to low maternal vitamin D status. It is hypothesized that dysregulated vitamin D action in uteroplacental tissues disrupts EVT invasion leading to malplacentation. Methods This study assessed the effects of the active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25-D3), and its precursor, 25-hydroxyvitamin D3 (25-D3), on primary human EVT isolated from first trimester pregnancies. Expression of EVT markers (cytokeratin-7, HLA-G), the vitamin D-activating enzyme (CYP27B1) and 1,25-D3 receptor (VDR) was assessed by immunocytochemistry. EVT responses following in vitro treatment with 1,25-D3 (0–10 nM) or 25-D3 (0–100 nM) for 48–60 h were assessed using quantitative RT-PCR (qRT-PCR) analysis of key target genes. Effects on EVT invasion through Matrigel® were quantified alongside zymographic analysis of secreted matrix metalloproteinases (MMPs). Effects on cell viability were assessed by measurement of MTT. Results EVT co-expressed mRNA and protein for CYP27B1 and VDR, and demonstrated induction of mRNA encoding vitamin D-responsive genes, 24-hydroxylase (CYP24A1) and cathelicidin following 1,25-D3 treatment. EVT could respond to 1,25-D3 and 25-D3, both of which significantly increased EVT invasion, with maximal effect at 1 nM 1,25-D3 (1.9-fold; p < 0.01) and 100 nM 25-D3 (2.2-fold; p < 0.05) respectively compared with untreated controls. This was accompanied by increased pro-MMP2 and pro-MMP9 secretion. The invasion was independent of cell viability, which remained unchanged. Discussion These data support a role for vitamin D in EVT invasion during human placentation and suggest that vitamin D-deficiency may contribute to impaired EVT invasion and pre-eclampsia

Exceptional molecular and coreceptor-requirement properties of molecular clones isolated from an Human Immunodeficiency Virus Type-1 subtype C infection

<p>Abstract</p> <p>Background</p> <p>The pathogenic significance of coreceptor switch in the viral infection of HIV-1 is not completely understood. This situation is more complex in subtype C infection where coreceptor switch is either absent or extremely rare. To gain insights into the mechanisms that underlie coreceptor requirement of subtype C, we screened several primary viral isolates and identified a clinical sample that demonstrated a potential to grow on standard T-cell lines with no detectable CCR5 expression. The subject was diagnosed with HIV-1 associated dementia in the absence of opportunistic infections of the brain. To isolate molecular clones from this virus, we devised a novel strategy based on anchor primers that target a sequence in the reverse transcriptase, highly conserved among diverse subtypes of HIV-1.</p> <p>Results</p> <p>Using this strategy, we isolated 8 full-length molecular clones from the donor. Two of the eight molecular clones, 03In94_D17 and 03In94_D24, (D17 and D24) generated replication-competent viruses. Phylogenetic analysis of the full-length viral sequences revealed that both clones were non-recombinant subtype C viruses. They contain intact open reading frames in all the viral proteins. Both the viral clones are endowed with several unique molecular and biological properties. The viral promoter of the clones is characterized by the presence of four NF-kB binding elements, a feature rarely seen in the subtype C HIV-1 LTR. Interestingly, we identified the coexistence of two different forms of Rev, a truncated form common to subtype C and a full-length form less common for this subtype, in both proviral and plasma virus compartments. An exceptional property of the viruses, atypical of subtype C, is their ability to use a wide range of coreceptors including CCR5, CXCR4, and several others tested. Sequence analysis of Env of D17 and D24 clones identified differences within the variable loops providing important clues for the expanded coreceptor use. The V1, V2 and V4 loops in both of the molecular clones are longer due to the insertion of several amino acid residues that generated potential N-linked glycosylation sites.</p> <p>Conclusion</p> <p>The exceptional biological and molecular properties of these clones make them invaluable tools to understand the unique pathogenic characteristics of subtype C.</p

Chiral structures of electric polarization vectors quantified by X-ray resonant scattering

Resonant elastic X-ray scattering (REXS) offers a unique tool to investigate solid-state systems providing spatial knowledge from diffraction combined with electronic information through the enhanced absorption process, allowing the probing of magnetic, charge, spin, and orbital degrees of spatial order together with electronic structure. A new promising application of REXS is to elucidate the chiral structure of electrical polarization emergent in a ferroelectric oxide superlattice in which the polarization vectors in the REXS amplitude are implicitly described through an anisotropic tensor corresponding to the quadrupole moment. Here, we present a detailed theoretical framework and analysis to quantitatively analyze the experimental results of Ti L-edge REXS of a polar vortex array formed in a PbTiO3/SrTiO3 superlattice. Based on this theoretical framework, REXS for polar chiral structures can become a useful tool similar to x-ray resonant magnetic scattering (XRMS), enabling a comprehensive study of both electric and magnetic REXS on the chiral structures.K.T.K., S.Y.P., and D.R.L acknowledge financial support by National Research Foundation of Korea (Grant No. NRF-2020R1A2C1009597, NRF-2019K1A3A7A09033387, and NRF-2021R1C1C1009494). M.M. and R.R. were supported by the Quantum Materials program from the Office of Basic Energy Sciences, US Department of Energy (DE-AC02-05CH11231). V.A.S., J.W.F., and L.W.M. acknowledge the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Award Number DE-SC-0012375 for support to study complex-oxide heterostructure with X-ray scattering. L.W.M. and R.R. acknowledge partial support from the Army Research Office under the ETHOS MURI via cooperative agreement W911NF-21-2-0162. J.Í. acknowledges financial support from the Luxembourg National Research Fund through project FNR/C18/MS/12705883/REFOX. M.A.P.G. was supported by the Czech Science Foundation (project no. 19-28594X). Diamond Light Source, UK, is acknowledged for beamtime on beamline I10 under proposal NT24797. Use of the Advanced Light Source, Lawrence Berkeley National Laboratory, was supported by the U.S. Department of Energy (DOE) under contract no. DE-AC02-05CH11231, and use of the Advanced Photon Source was supported by DOE’s Office of Science under contract DE-AC02-06CH11357

Manipulating chiral-spin transport with ferroelectric polarization

A collective excitation of the spin structure in a magnetic insulator can transmit spin-angular momentum with negligible dissipation. This quantum of a spin wave, introduced more than nine decades ago, has always been manipulated through magnetic dipoles, (i.e., timereversal symmetry). Here, we report the experimental observation of chiral-spin transport in multiferroic BiFeO3, where the spin transport is controlled by reversing the ferroelectric polarization (i.e., spatial inversion symmetry). The ferroelectrically controlled magnons produce an unprecedented ratio of up to 18% rectification at room temperature. The spin torque that the magnons in BiFeO3 carry can be used to efficiently switch the magnetization of adja-cent magnets, with a spin-torque efficiency being comparable to the spin Hall effect in heavy metals. Utilizing such a controllable magnon generation and transmission in BiFeO3, an alloxide, energy-scalable logic is demonstrated composed of spin-orbit injection, detection, and magnetoelectric control. This observation opens a new chapter of multiferroic magnons and paves an alternative pathway towards low-dissipation nanoelectronics