Construction of optimal witness for unknown two-qubit entanglement

Whether entanglement in a state can be detected, distilled, and quantified without full state reconstruction is a fundamental open problem. We demonstrate a new scheme encompassing these three tasks for arbitrary two-qubit entanglement, by constructing the optimal entanglement witness for polarization-entangled mixed-state photon pairs without full state reconstruction. With better efficiency than quantum state tomography, the entanglement is maximally distilled by newly developed tunable polarization filters, and quantified by the expectation value of the witness, which equals the concurrence. This scheme is extendible to multiqubit Greenberger-Horne-Zeilinger entanglement.Comment: Phys. Rev. Lett. 105, 230404 (2010); supplementary information (OWitness_sup.pdf) is included in source zip fil

Structural and functional basis for inhibition of erythrocyte invasion by antibodies that target Plasmodium falciparum EBA-175

Disrupting erythrocyte invasion by Plasmodium falciparum is an attractive approach to combat malaria. P. falciparum EBA-175 (PfEBA-175) engages the host receptor Glycophorin A (GpA) during invasion and is a leading vaccine candidate. Antibodies that recognize PfEBA-175 can prevent parasite growth, although not all antibodies are inhibitory. Here, using x-ray crystallography, small-angle x-ray scattering and functional studies, we report the structural basis and mechanism for inhibition by two PfEBA-175 antibodies. Structures of each antibody in complex with the PfEBA-175 receptor binding domain reveal that the most potent inhibitory antibody, R217, engages critical GpA binding residues and the proposed dimer interface of PfEBA-175. A second weakly inhibitory antibody, R218, binds to an asparagine-rich surface loop. We show that the epitopes identified by structural studies are critical for antibody binding. Together, the structural and mapping studies reveal distinct mechanisms of action, with R217 directly preventing receptor binding while R218 allows for receptor binding. Using a direct receptor binding assay we show R217 directly blocks GpA engagement while R218 does not. Our studies elaborate on the complex interaction between PfEBA-175 and GpA and highlight new approaches to targeting the molecular mechanism of P. falciparum invasion of erythrocytes. The results suggest studies aiming to improve the efficacy of blood-stage vaccines, either by selecting single or combining multiple parasite antigens, should assess the antibody response to defined inhibitory epitopes as well as the response to the whole protein antigen. Finally, this work demonstrates the importance of identifying inhibitory-epitopes and avoiding decoy-epitopes in antibody-based therapies, vaccines and diagnostics

Spatial Regulation of ABCG25, an ABA Exporter, Is an Important Component of the Mechanism Controlling Cellular ABA Levels

The phytohormone abscisic acid (ABA) plays crucial roles in various physiological processes, including responses to abiotic stresses, in plants. Recently, multiple ABA transporters were identified. The loss-of-function and gain-of-function mutants of these transporters show altered ABA sensitivity and stomata regulation, highlighting the importance of ABA transporters in ABA-mediated processes. However, how the activity of these transporters is regulated remains elusive. Here, we show that spatial regulation of ATP BINDING CASETTE G25 (ABCG25), an ABA exporter, is an important mechanism controlling its activity. ABCG25, as a soluble green fluorescent protein (sGFP) fusion, was subject to posttranslational regulation via clathrin-dependent and adaptor protein complex-2-dependent endocytosis followed by trafficking to the vacuole. The levels of sGFP: ABCG25 at the plasma membrane (PM) were regulated by abiotic stresses and exogenously applied ABA; PM-localized sGFP: ABCG25 decreased under abiotic stress conditions via activation of endocytosis in an ABA-independent manner, but increased upon application of exogenous ABA via activation of recycling from early endosomes in an ABA-dependent manner. Based on these findings, we propose that the spatial regulation of ABCG25 is an important component of the mechanism by which plants fine-tune cellular ABA levels according to cellular and environmental conditions.1197Ysciescopu

Robust, reproducible, industrialized, standard membrane feeding assay for assessing the transmission blocking activity of vaccines and drugs against Plasmodium falciparum.

BackgroundA vaccine that interrupts malaria transmission (VIMT) would be a valuable tool for malaria control and elimination. One VIMT approach is to identify sexual erythrocytic and mosquito stage antigens of the malaria parasite that induce immune responses targeted at disrupting parasite development in the mosquito. The standard Plasmodium falciparum membrane-feeding assay (SMFA) is used to assess transmission-blocking activity (TBA) of antibodies against candidate immunogens and of drugs targeting the mosquito stages. To develop its P. falciparum sporozoite (SPZ) products, Sanaria has industrialized the production of P. falciparum-infected Anopheles stephensi mosquitoes, incorporating quantitative analyses of oocyst and P. falciparum SPZ infections as part of the manufacturing process.MethodsThese capabilities were exploited to develop a robust, reliable, consistent SMFA that was used to assess 188 serum samples from animals immunized with the candidate vaccine immunogen, Pfs25, targeting P. falciparum mosquito stages. Seventy-four independent SMFAs were performed. Infection intensity (number of oocysts/mosquito) and infection prevalence (percentage of mosquitoes infected with oocysts) were compared between mosquitoes fed cultured gametocytes plus normal human O(+) serum (negative control), anti-Pfs25 polyclonal antisera (MRA39 or MRA38, at a final dilution in the blood meal of 1:54 as positive control), and test sera from animals immunized with Pfs25 (at a final dilution in the blood meal of 1:9).ResultsSMFA negative controls consistently yielded high infection intensity (mean = 46.1 oocysts/midgut, range of positives 3.7-135.6) and infection prevalence (mean = 94.2%, range 71.4-100.0) and in positive controls, infection intensity was reduced by 81.6% (anti-Pfs25 MRA39) and 97.0% (anti-Pfs25 MRA38), and infection prevalence was reduced by 12.9 and 63.5%, respectively. A range of TBAs was detected among the 188 test samples assayed in duplicate. Consistent administration of infectious gametocytes to mosquitoes within and between assays was achieved, and the TBA of anti-Pfs25 control antibodies was highly reproducible.ConclusionsThese results demonstrate a robust capacity to perform the SMFA in a medium-to-high throughput format, suitable for assessing large numbers of experimental samples of candidate antibodies or drugs

Single-electron transistor based on a silicon-on-insulator quantum wire fabricated by a side-wall patterning method

We propose and implement a promising fabrication technology for geometrically well-defined single-electron transistors based on a silicon-on-insulator quantum wire and side-wall depletion gates. The 30-nm-wide silicon quantum wire is defined by a combination of conventional photolithography and process technology, called a side-wall patterning method, and depletion gates for two tunnel junctions are formed by the doped polycrystalline silicon sidewall. The good uniformity of the wire suppresses unexpected potential barriers. The fabricated device shows clear single-electron tunneling phenomena by an electrostatically defined single island at liquid nitrogen temperature and insensitivity of the Coulomb oscillation period to gate bias conditions.open252

Proteome-wide analysis of a malaria vaccine study reveals personalized humoral immune profiles in Tanzanian adults

Tanzanian adult male volunteers were immunized by direct venous inoculation with radiation-attenuated, aseptic, purified, cryopreserved; Plasmodium falciparum; (Pf) sporozoites (PfSPZ Vaccine) and protective efficacy assessed by homologous controlled human malaria infection (CHMI). Serum immunoglobulin G (IgG) responses were analyzed longitudinally using a Pf protein microarray covering 91% of the proteome, providing first insights into naturally acquired and PfSPZ Vaccine-induced whole parasite antibody profiles in malaria pre-exposed Africans. Immunoreactivity was identified against 2239 functionally diverse Pf proteins, showing a wide breadth of humoral response. Antibody-based immune 'fingerprints' in these individuals indicated a strong person-specific immune response at baseline, with little changes in the overall humoral immunoreactivity pattern measured after immunization. The moderate increase in immunogenicity following immunization and the extensive and variable breadth of humoral immune response observed in the volunteers at baseline suggest that pre-exposure reduces vaccine-induced antigen reactivity in unanticipated ways

Continuous cropping of endangered therapeutic plants via electron beam soil treatment and neutron tomography

Various medicinal plants are threatened with extinction owing to their over exploitation and the prevalence of soil borne pathogens. In this study, soils infected with root rot pathogens, which prevent continuous cropping, were treated with an electron beam. The level of soil borne fungus was reduced to amp; 8804;0.01 by soil electron beam treatment without appreciable effects on the levels of antagonistic microorganism or on the physicochemical properties of the soil. The survival rate of 4 year old plant was higher in electron beam treated soil 81.0 than in fumigated 62.5 , virgin 78 , or untreatedreplanting soil 0 . Additionally, under various soils conditions, neutron tomography permitted the monitoring of plant health and the detection of root pathological changes over a period of 4 6 years by quantitatively measuring root water content in situ. These methods allow continual cropping on the same soil without pesticide treatment. This is a major step toward the environmentally friendly production of endangered therapeutic herb

Risk factors of COVID-19 mortality: a systematic review of current literature and lessons from recent retracted articles

OBJECTIVE: Recently, two influential articles that reported the association of (hydroxy)chloroquine or angiotensin converting enzyme (ACE) inhibitors and coronavirus disease 2019 (COVID-19) mortality were retracted due to significant methodological issues. Therefore, we aimed to analyze the same clinical issues through an improved research method and to find out the differences from the retracted papers. We systematically reviewed pre-existing literature, and compared the results with those of the retracted papers to gain a novel insight. MATERIALS AND METHODS: We extracted common risk factors identified in two retracted papers, and conducted relevant publication search until June 26, 2020 in PubMed. Then, we analyzed the risk factors for COVID-19 mortality and compared them to those of the retracted papers. RESULTS: Our systematic review demonstrated that most demographic and clinical risk factors for COVID-19 mortality were similar to those of the retracted papers. However, while the retracted paper indicated that both (hydroxy)chloroquine monotherapy and combination therapy with macrolide were associated with higher risk of mortality, our study showed that only combination therapy of hydroxychloroquine and macrolide was associated with higher risk of mortality (odds ratio 2.33; 95% confidence interval 1.63-3.34). In addition, our study demonstrated that use of ACE inhibitors or angiotensin receptor blockers (ARBs) was associated with reduced risk of mortality (0.77; 0.65-0.91). CONCLUSIONS: When analyzing the same clinical issues with the two retracted papers through a systematic review of randomized controlled trials and relevant cohort studies, we found out that (hydroxy)chloroquine monotherapy was not associated with higher risk of mortality, and that the use of ACE inhibitors or ARBs was associated with reduced risk of mortality in COVID-19 patients

Direct comparison of phase-space distributions of K- and K+ mesons in heavy-ion collisions at SIS energies - evidence for in-medium modifications of kaons ?

The ratio of K- to K+ meson yields has been measured in the systems RuRu at 1.69 A GeV, Ru+Zr at 1.69 A GeV, and Ni+Ni at 1.93 A GeV incident beam kinetic energy. The yield ratio is observed to vary across the measured phase space. Relativistic transport-model calculations indicate that the data are best understood if in-medium modifications of the kaons are taken into account.Comment: 14 pages including 3 figure

Delineation of Stage Specific Expression of Plasmodium falciparum EBA-175 by Biologically Functional Region II Monoclonal Antibodies

EBA-175 binds its receptor sialic acids on glycophorin A when invading erythrocytes. The receptor-binding region (RII) contains two cysteine-rich domains with similar cysteine motifs (F1 and F2). Functional relationships between F1 and F2 domains and characterization of EBA-175 were studied using specific monoclonal antibodies (mAbs) against these domains..The role of the F1 and F2 domains in erythrocyte invasion and binding was elucidated with mAbs. These mAbs interfere with native EBA-175 binding to erythrocyte in a synergistic fashion. The stage specific expression of EBA-175 showed that the primary focus of activity was the merozoite stage. A recombinant RII protein vaccine consisting of both F1 and F2 domains that could induce synergistic activity should be optimal for induction of antibody responses that interfere with merozoite invasion of erythrocytes