709 research outputs found
Feasibility study - 30 watt per pound roll-up solar array Quarterly technical report, 1 Jul. - 30 Sep. 1967
Configuration, rod tradeoff, and deployment parameter studies for design of solar panel arra
Mosaic patterns of diversification dynamics following the colonization of Melanesian islands
The fate of newly settled dispersers on freshly colonized oceanic islands is a central theme of island biogeography. The emergence of increasingly sophisticated methods of macroevolutionary pattern inference paves the way for a deeper understanding of the mechanisms governing these diversification patterns on lineages following their colonization of oceanic islands. Here we infer a comprehensive molecular phylogeny for Melanesian Exocelina diving beetles. Recent methods in historical biogeography and diversification rate inference were then used to investigate the evolution of these insects in space and time. An Australian origin in the mid-Miocene was followed by independent colonization events towards New Guinea and New Caledonia in the late Miocene. One colonization of New Guinea led to a large radiation of >150 species and 3 independent colonizations of New Caledonia gave rise to about 40 species. The comparably late colonizations of Vanuatu, Hawaii and China left only one or two species in each region. The contrasting diversification trajectories of these insects on Melanesian islands are likely accounted for by island size, age and availability of ecological opportunities during the colonization stage
Pleistocene climate change promoted rapid diversification of aquatic invertebrates in Southeast Australia
Background: The Pleistocene Ice Ages were the most recent geohistorical event of major global impact, but their consequences for most parts of the Southern hemisphere remain poorly known. We investigate a radiation of ten species of Sternopriscus, the most species-rich genus of epigean Australian diving beetles. These species are distinct based on genital morphology but cannot be distinguished readily by mtDNA and nDNA because of genotype sharing caused by incomplete lineage sorting. Their genetic similarity suggests a Pleistocene origin. Results: We use a dataset of 3858 bp of mitochondrial and nuclear DNA to reconstruct a phylogeny of Sternopriscus using gene and species trees. Diversification analyses support the finding of a recent rapid speciation event with estimated speciation rates of up to 2.40 species per MY, which is considerably higher than the proposed average rate of 0.16 species per MY for insects. Additionally, we use ecological niche modeling and analyze data on habitat preferences to test for niche divergence between species of the recent Sternopriscus radiation. These analyses show that the species can be characterized by a set of ecological variables referring to habitat, climate and altitude. Conclusions: Our results suggest that the repeated isolation of populations in glacial refugia might have led to divergent ecological adaptations and the fixation of morphological traits supporting reproductive isolation and therefore may have promoted speciation. The recent Sternopriscus radiation fulfills many characteristics of a species flock and would be the first described example of an aquatic insect species flock. We argue that the species of this group may represent a stage in speciation past the species flock condition because of their mostly broad and often non-overlapping ranges and preferences for different habitat types
Local probing of ionic diffusion by electrochemical strain microscopy: spatial resolution and signal formation mechanisms
Electrochemical insertion-deintercalation reactions are typically associated
with significant change of molar volume of the host compound. This strong
coupling between ionic currents and strains underpins image formation
mechanisms in electrochemical strain microscopy (ESM), and allows exploring the
tip-induced electrochemical processes locally. Here we analyze the signal
formation mechanism in ESM, and develop the analytical description of operation
in frequency and time domains. The ESM spectroscopic modes are compared to
classical electrochemical methods including potentiostatic and galvanostatic
intermittent titration (PITT and GITT), and electrochemical impedance
spectroscopy (EIS). This analysis illustrates the feasibility of spatially
resolved studies of Li-ion dynamics on the sub-10 nanometer level using
electromechanical detection.Comment: 49 pages, 17 figures, 4 tables, 3 appendices, to be submitted to J.
Appl. Phys
Macroevolution of hyperdiverse flightless beetles reflects the complex geological history of the Sunda Arc
The Sunda Arc forms an almost continuous chain of islands and thus a potential dispersal corridor between mainland Southeast Asia and Melanesia. However, the Sunda Islands have rather different geological histories, which might have had an important impact on actual dispersal routes and community assembly. Here, we reveal the biogeographical history of hyperdiverse and flightless Trigonopterus weevils. Different approaches to ancestral area reconstruction suggest a complex east to west range expansion. Out of New Guinea, Trigonopterus repeatedly reached the Moluccas and Sulawesi transgressing Lydekker′s Line. Sulawesi repeatedly acted as colonization hub for different segments of the Sunda Arc. West Java, East Java and Bali are recognized as distinct biogeographic areas. The timing and diversification of species largely coincides with the geological chronology of island emergence. Colonization was not inhibited by traditional biogeographical boundaries such as Wallace’s Line. Rather, colonization patterns support distance dependent dispersal and island age limiting dispersal
On the possibility of magnetic Weyl fermions in non-symmorphic compound PtFeSb
Weyl fermions are expected to exhibit exotic physical properties such as the
chiral anomaly, large negative magnetoresistance or Fermi arcs. Recently a new
platform to realize these fermions has been introduced based on the appearance
of a three-fold band crossing at high symmetry points of certain space groups.
These band crossings are composed of two linearly dispersed bands that are
topologically protected by a Chern number, and a at band with no topological
charge. In this paper we present a new way of inducing two kinds of Weyl
fermions, based on two- and three-fold band crossings, in the non-symmorphic
magnetic material PtFeSb. By means of density functional theory calculations
and group theory analysis we show that magnetic order can split a six-fold
degeneracy enforced by non-symmoprhic symmetry to create three-fold or two-fold
degenerate Weyl nodes. We also report on the synthesis of a related phase
potentially containing two-fold degenerate magnetic Weyl points and extend our
group theory analysis to that phase. This is the first study showing that
magnetic ordering has the potential to generate new threefold degenerate Weyl
nodes, advancing the understanding of magnetic interactions in topological
materials.Comment: 8 pages, 5 figure
Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy.
BACKGROUND
Virus-like particle (VLP) Peanut is a novel immunotherapeutic vaccine candidate for the treatment of peanut allergy. The active pharmaceutical ingredient represents cucumber mosaic VLPs (CuMVTT -VLPs) that are genetically fused with one of the major peanut allergens, Ara h 2 (CuMVTT -Ara h 2). We previously demonstrated the immunogenicity and the protective capacity of VLP Peanut-based immunization in a murine model for peanut allergy. Moreover, a Phase I clinical trial has been initiated using VLP Peanut material manufactured following a GMP-compliant manufacturing process. Key product characterization studies were undertaken here to understand the role and contribution of critical quality attributes that translate as predictive markers of immunogenicity and protective efficacy for clinical vaccine development.
METHOD
The role of prokaryotic RNA encapsulated within VLP Peanut on vaccine immunogenicity was assessed by producing a VLP Peanut batch with a reduced RNA content (VLP Peanut low RNA). Immunogenicity and peanut allergen challenge studies were conducted with VLP Peanut low RNA, as well as with VLP Peanut in WT and TLR 7 KO mice. Furthermore, mass spectrometry and SDS-PAGE based methods were used to determine Ara h 2 antigen density on the surface of VLP Peanut particles. This methodology was subsequently applied to investigate the relationship between Ara h 2 antigen density and immunogenicity of VLP Peanut.
RESULTS
A TLR 7 dependent formation of Ara h 2 specific high-avidity IgG antibodies, as well as a TLR 7 dependent change in the dominant IgG subclass, was observed following VLP Peanut vaccination, while total allergen-specific IgG remained relatively unaffected. Consistently, a missing TLR 7 signal caused only a weak decrease in allergen tolerability after vaccination. In contrast, a reduced RNA content for VLP Peanut resulted in diminished total Ara h 2 specific IgG responses, followed by a significant impairment in peanut allergen tolerability. The discrepant effect on allergen tolerance caused by an absent TLR 7 signal versus a reduced RNA content is explained by the observation that VLP Peanut-derived RNA not only stimulates TLR 7 but also TLR 3. Additionally, a strong correlation was observed between the number of Ara h 2 antigens displayed on the surface of VLP Peanut particles and the vaccine's immunogenicity and protective capacity.
CONCLUSIONS
Our findings demonstrate that prokaryotic RNA encapsulated within VLP Peanut, including antigen density of Ara h 2 on viral particles, are key contributors to the immunogenicity and protective capacity of the vaccine. Thus, antigenicity and RNA content are two critical quality attributes that need to be determined at the stage of manufacturing, providing robust information regarding the immunogenicity and protective capacity of VLP Peanut in the mouse which has translational relevance to the human setting
CP asymmetries in penguin-induced B decays in general left-right models
We study CP asymmetries in penguin-induced b -> s\bar{s}s decays in general
left-right models without imposing manifest or pseudomanifest left-right
symmetry. Using the effective Hamiltonian approach, we evaluate CP asymmetries
in B^\pm -> \phi K^{(\ast)\pm} decays as well as mixing induced B meson decays
B -> J/\psi K_s and B -> \phi K_s decays. Based on recent measurements
revealing large CP violation, we show that nonmanifest type model is more
favored than manifest or pseudomanifest type.Comment: 16 pages, 12 eps figure
The next generation virus-like particle platform for the treatment of peanut allergy.
BACKGROUND
Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus-like particles (VLPs), is described here for the treatment of peanut allergy.
METHODS AND RESULTS
VLP Peanut consist of two proteins: a capsid subunit derived from Cucumber mosaic virus engineered with a universal T cell epitope (CuMVTT ) and a CuMVTT subunit fused with peanut allergen Ara h 2 (CuMVTT -Ara h 2), forming mosaic VLPs. Immunizations with VLP Peanut in both naïve and peanut-sensitised mice resulted in a significant anti-Ara h 2 IgG response. Local and systemic protection induced by VLP Peanut were established in mouse models for peanut allergy following prophylactic, therapeutic and passive immunizations. Inhibition of FcγRIIb function resulted in a loss of protection, confirming the crucial role of the receptor in conferring cross protection against peanut allergens other than Ara h 2.
CONCLUSION
VLP Peanut can be delivered to peanut-sensitized mice without triggering allergic reactions, whilst remaining highly immunogenic and offering protection against all peanut allergens. In addition, vaccination ablates allergic symptoms upon allergen challenge. Moreover, the prophylactic immunization setting conferred the protection against subsequent peanut-induced anaphylaxis, showing the potential for preventive vaccination. This highlights the effectiveness of VLP Peanut as a prospective break-through immunotherapy vaccine candidate towards peanut allergy. VLP Peanut has now entered clinical development with the study PROTECT
The next generation virus‐like particle platform for the treatment of peanut allergy
Background: Allergy to peanut is one of the leading causes of anaphylactic reactions among food allergic patients. Immunization against peanut allergy with a safe and protective vaccine holds a promise to induce durable protection against anaphylaxis caused by exposure to peanut. A novel vaccine candidate (VLP Peanut), based on virus‐like particles (VLPs), is described here for the treatment of peanut allergy.
Methods and Results: VLP Peanut consists of two proteins: a capsid subunit derived from Cucumber mosaic virus engineered with a universal T‐cell epitope (CuMV) and a CuMV subunit fused with peanut allergen Ara h 2 (CuMV‐Ara h 2), forming mosaic VLPs. Immunizations with VLP Peanut in both naïve and peanut‐sensitized mice resulted in a significant anti‐Ara h 2 IgG response. Local and systemic protection induced by VLP Peanut were established in mouse models for peanut allergy following prophylactic, therapeutic, and passive immunizations. Inhibition of FcγRIIb function resulted in a loss of protection, confirming the crucial role of the receptor in conferring cross protection against peanut allergens other than Ara h 2.
Conclusion: VLP Peanut can be delivered to peanut‐sensitized mice without triggering allergic reactions, while remaining highly immunogenic and offering protection against all peanut allergens. In addition, vaccination ablates allergic symptoms upon allergen challenge. Moreover, the prophylactic immunization setting conferred the protection against subsequent peanut‐induced anaphylaxis, showing the potential for preventive vaccination. This highlights the effectiveness of VLP Peanut as a prospective break‐through immunotherapy vaccine candidate toward peanut allergy. VLP Peanut has now entered clinical development with the study PROTECT
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