2,991 research outputs found
The isodiametric problem with lattice-point constraints
In this paper, the isodiametric problem for centrally symmetric convex bodies
in the Euclidean d-space R^d containing no interior non-zero point of a lattice
L is studied. It is shown that the intersection of a suitable ball with the
Dirichlet-Voronoi cell of 2L is extremal, i.e., it has minimum diameter among
all bodies with the same volume. It is conjectured that these sets are the only
extremal bodies, which is proved for all three dimensional and several
prominent lattices.Comment: 12 pages, 4 figures, (v2) referee comments and suggestions
incorporated, accepted in Monatshefte fuer Mathemati
Safety and Security Co-engineering and Argumentation Framework
Automotive systems become increasingly complex due to their functional range and data exchange with the outside world. Until now, functional safety of such safety-critical electrical/electronic systems has been covered successfully. However, the data exchange requires interconnection across trusted boundaries of the vehicle. This leads to security issues like hacking and malicious attacks against interfaces, which could bring up new types of safety issues. Before mass-production of automotive systems, arguments supported by evidences are required regarding safety and security. Product engineering must be compliant to specific standards and must support arguments that the system is free of unreasonable risks.
This paper shows a safety and security co-engineering framework, which covers standard compliant process derivation and management, and supports product specific safety and security co-analysis. Furthermore, we investigate process- and product-related argumentation and apply the approach to an automotive use case regarding safety and security.This work is supported by the projects EMC2 and AMASS. Research leading to these results has received funding from the EU ARTEMIS Joint Undertaking under grant agreement no. 621429 (project EMC2), project AMASS (H2020-ECSEL no 692474; Spain’s MINECO ref. PCIN-2015-262) and from the COMET K2 - Competence Centres for Excellent Technologies Programme of the Austrian Federal Ministry for Transport, Innovation and Technology (bmvit), the Austrian Federal Ministry of Science, Research and Economy (bmwfw), the Austrian Research Promotion Agency (FFG), the Province of Styria and the Styrian Business Promotion Agency (SFG)
Characterisation of a highly potent and near pan-neutralising anti-HIV monoclonal antibody expressed in tobacco plants
Background
HIV remains one of the most important health issues worldwide, with almost 40 million people living with HIV. Although patients develop antibodies against the virus, its high mutation rate allows evasion of immune responses. Some patients, however, produce antibodies that are able to bind to, and neutralise different strains of HIV. One such ‘broadly neutralising’ antibody is ‘N6’. Identified in 2016, N6 can neutralise 98% of HIV-1 isolates with a median IC50 of 0.066 µg/mL. This neutralisation breadth makes N6 a very promising therapeutic candidate.
Results
N6 was expressed in a glycoengineered line of N. benthamiana plants (pN6) and compared to the mammalian cell-expressed equivalent (mN6). Expression at 49 mg/kg (fresh leaf tissue) was achieved in plants, although extraction and purification are more challenging than for most plant-expressed antibodies. N-glycoanalysis demonstrated the absence of xylosylation and a reduction in α(1,3)-fucosylation that are typically found in plant glycoproteins. The N6 light chain contains a potential N-glycosylation site, which was modified and displayed more α(1,3)-fucose than the heavy chain. The binding kinetics of pN6 and mN6, measured by surface plasmon resonance, were similar for HIV gp120. pN6 had a tenfold higher affinity for FcγRIIIa, which was reflected in an antibody-dependent cellular cytotoxicity assay, where pN6 induced a more potent response from effector cells than that of mN6. pN6 demonstrated the same potency and breadth of neutralisation as mN6, against a panel of HIV strains.
Conclusions
The successful expression of N6 in tobacco supports the prospect of developing a low-cost, low-tech production platform for a monoclonal antibody cocktail to control HIV in low-to middle income countries
Thermophysical properties of the lanthanide sesquisulfides. II. Schottky contributions and magnetic and electronic properties of γ‐phase Pr2S3, Tb2S3, and Dy2S3
Heat‐capacity measurements by adiabatic equilibrium calorimetry are reported for γ‐phase Pr2S3, Tb2S3, and Dy2S3 between 5 and 350 K. Highly purified samples were prepared and their composition verified by chemical analysis. Precision lattice parameters were determined for each compound and are compared with literature values. The total heat capacity has been resolved into lattice, magnetic, and Schottky components by a volumetric approach. The experimental Schottky contributions accord with the calculated curves based on the crystal‐field splitting of the 2S+1LJ ground state of the lanthanide ions occupying sites of S4 symmetry in the Th3P4 lattice. The individual crystal‐field electronic energy levels have been obtained in part from an analysis of the hot‐band data observed in the absorption spectra of Pr2S3, Tb2S3, and Dy2S3, and from a calculated splitting in which the crystal‐field parameters Bkm, were determined from a lattice‐sum calculation. Molar thermodynamic properties are reported for all three compounds. The entropy at 298.15 K {S0−S0 (7 K)}, is 22.78R, 22.93R, and 23.36R, for γ‐phase Pr2S3, Tb2S3, and Dy2S3, respectively.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70592/2/JCPSA6-95-3-1964-1.pd
Interaction of Disulfiram with Antiretroviral Medications: Efavirenz Increases While Atazanavir Decreases Disulfiram Effect on Enzymes of Alcohol Metabolism
Background and Objectives
Alcohol abuse complicates treatment of HIV disease and is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram (DIS), are infrequently utilized in co-occurring HIV and alcohol use disorders possibly related to concerns about drug interactions between antiretroviral (ARV) medications and DIS.
Method
This pharmacokinetics study (n = 40) examined the effect of DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) and the effect of these ARV medications on DIS metabolism and aldehyde dehydrogenase (ALDH) activity which mediates the DIS-alcohol reaction.
Results
EFV administration was associated with decreased S-Methyl-N-N-diethylthiocarbamate (DIS carbamate), a metabolite of DIS (p = .001) and a precursor to the metabolite responsible for ALDH inhibition, S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC–MeSO). EFV was associated with increased DIS inhibition of ALDH activity relative to DIS alone administration possibly as a result of EFV-associated induction of CYP 3A4 which metabolizes the carbamate to DETC–MeSO (which inhibits ALDH). Conversely, ATV co-administration reduced the effect of DIS on ALDH activity possibly as a result of ATV inhibition of CYP 3A4. DIS administration had no significant effect on any ARV studied.
Discussion/Conclusions
ATV may render DIS ineffective in treatment of alcoholism.
Future Directions
DIS is infrequently utilized in HIV-infected individuals due to concerns about adverse interactions and side effects. Findings from this study indicate that, with ongoing clinical monitoring, DIS should be reconsidered given its potential efficacy for alcohol and potentially, cocaine use disorders, that may occur in this population. (Am J Addict 2014;23:137–144
Is cannabis use a contributory cause of psychosis?
Objective: To assess whether cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychosis in that it may precipitate psychosis in vulnerable individuals. Method: We reviewed longitudinal studies of adolescents and young adults that examined the relations between self-reported cannabis use and the risk of diagnosis with a psychosis or of reporting psychotic symptoms. We also reviewed studies that controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. We assessed evidence for the biological plausibility of a contributory causal relation. Results: Evidence from 6 longitudinal studies in 5 countries shows that regular cannabis use predicts an increased risk of a schizophrenia diagnosis or of reporting symptoms of psychosis. These relations persisted after controlling for confounding variables, such as personal characteristics and other drug use. The relation did not seem to be a result of cannabis use to self-medicate symptoms of psychosis. A contributory causal relation is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter systems with which the cannabinoid system interacts, as demonstrated by animal studies and one human provocation study. Conclusion: It is most plausible that cannabis use precipitates schizophrenia in individuals who are vulnerable because of a personal or family history of schizophrenia
Using Neural Networks for Relation Extraction from Biomedical Literature
Using different sources of information to support automated extracting of
relations between biomedical concepts contributes to the development of our
understanding of biological systems. The primary comprehensive source of these
relations is biomedical literature. Several relation extraction approaches have
been proposed to identify relations between concepts in biomedical literature,
namely, using neural networks algorithms. The use of multichannel architectures
composed of multiple data representations, as in deep neural networks, is
leading to state-of-the-art results. The right combination of data
representations can eventually lead us to even higher evaluation scores in
relation extraction tasks. Thus, biomedical ontologies play a fundamental role
by providing semantic and ancestry information about an entity. The
incorporation of biomedical ontologies has already been proved to enhance
previous state-of-the-art results.Comment: Artificial Neural Networks book (Springer) - Chapter 1
Seagrass can mitigate negative ocean acidification effects on calcifying algae
The ultimate effect that ocean acidification (OA) and warming will have on the physiology of calcifying algae is still largely uncertain. Responses depend on the complex interactions between seawater chemistry, global/local stressors and species-specific physiologies. There is a significant gap regarding the effect that metabolic interactions between coexisting species may have on local seawater chemistry and the concurrent effect of OA. Here, we manipulated CO2 and temperature to evaluate the physiological responses of two common photoautotrophs from shallow tropical marine coastal ecosystems in Brazil: the calcifying alga Halimeda cuneata, and the seagrass Halodule wrightii. We tested whether or not seagrass presence can influence the calcification rate of a widespread and abundant species of Halimeda under OA and warming. Our results demonstrate that under elevated CO2, the high photosynthetic rates of H. wrightii contribute to raise H. cuneata calcification more than two-fold and thus we suggest that H. cuneata populations coexisting with H. wrightii may have a higher resilience to OA conditions. This conclusion supports the more general hypothesis that, in coastal and shallow reef environments, the metabolic interactions between calcifying and non-calcifying organisms are instrumental in providing refuge against OA effects and increasing the resilience of the more OA-susceptible species.E.B. would like to thank the Coordenação de Aperfeiçoamento de Pessoas de Nível Superior (CAPES) for Masters
funding. Funding for this project came from the Synergism grant (CNPq 407365/2013-3). We extend our thanks
to the Brazil-based Projeto Coral Vivo and its sponsor PetroBras Ambiental for providing the Marine Mesocosm
structure and experimental assistance.info:eu-repo/semantics/publishedVersio
Quantum control of proximal spins using nanoscale magnetic resonance imaging
Quantum control of individual spins in condensed matter systems is an
emerging field with wide-ranging applications in spintronics, quantum
computation, and sensitive magnetometry. Recent experiments have demonstrated
the ability to address and manipulate single electron spins through either
optical or electrical techniques. However, it is a challenge to extend
individual spin control to nanoscale multi-electron systems, as individual
spins are often irresolvable with existing methods. Here we demonstrate that
coherent individual spin control can be achieved with few-nm resolution for
proximal electron spins by performing single-spin magnetic resonance imaging
(MRI), which is realized via a scanning magnetic field gradient that is both
strong enough to achieve nanometric spatial resolution and sufficiently stable
for coherent spin manipulations. We apply this scanning field-gradient MRI
technique to electronic spins in nitrogen-vacancy (NV) centers in diamond and
achieve nanometric resolution in imaging, characterization, and manipulation of
individual spins. For NV centers, our results in individual spin control
demonstrate an improvement of nearly two orders of magnitude in spatial
resolution compared to conventional optical diffraction-limited techniques.
This scanning-field-gradient microscope enables a wide range of applications
including materials characterization, spin entanglement, and nanoscale
magnetometry.Comment: 7 pages, 4 figure
Optically modulated magnetic resonance of erbium implanted silicon
Er implanted Si is an important candidate for quantum and photonic applications, but the Er centres involved are poorly understood, which has hindered development of these applications. Here we present the first measurement of the crystal field splitting of the 4I13/2 manifold of Er implanted Si, using a technique we call optically modulated magnetic resonance (OMMR). Crystal field analysis allows us to determine that this splitting originates from a photoluminescence (PL) active O coordinated Er centre with orthorhombic symmetry, which is highly localised with, and magically coupled to, an electron paramagnetic resonance (ERP) active O coordinated Er centre with monoclinic symmetry. The orthorhombic centre has a g-factor in agreement with previous Zeeman measurements, and is associated with a previously unreported acceptor state at ~ Ev+425 cm-1, showing that Er in Si is amphoteric, and not a pure donor, as previously thought. The OMMR mechanism involves transitions from this acceptor state to the 4I13/2 manifold, followed by relaxation to the Zeeman ground state
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