7,821 research outputs found
Creature forcing and large continuum: The joy of halving
For let be the minimal number of
uniform -splitting trees needed to cover the uniform -splitting tree,
i.e., for every branch of the -tree, one of the -trees contains
. Let be the dual notion: For every branch , one of
the -trees guesses infinitely often. We show that it is consistent
that
for continuum many pairwise different cardinals and suitable
pairs . For the proof we introduce a new mixed-limit
creature forcing construction
Content Delivery Latency of Caching Strategies for Information-Centric IoT
In-network caching is a central aspect of Information-Centric Networking
(ICN). It enables the rapid distribution of content across the network,
alleviating strain on content producers and reducing content delivery
latencies. ICN has emerged as a promising candidate for use in the Internet of
Things (IoT). However, IoT devices operate under severe constraints, most
notably limited memory. This means that nodes cannot indiscriminately cache all
content; instead, there is a need for a caching strategy that decides what
content to cache. Furthermore, many applications in the IoT space are
timesensitive; therefore, finding a caching strategy that minimises the latency
between content request and delivery is desirable. In this paper, we evaluate a
number of ICN caching strategies in regards to latency and hop count reduction
using IoT devices in a physical testbed. We find that the topology of the
network, and thus the routing algorithm used to generate forwarding
information, has a significant impact on the performance of a given caching
strategy. To the best of our knowledge, this is the first study that focuses on
latency effects in ICN-IoT caching while using real IoT hardware, and the first
to explicitly discuss the link between routing algorithm, network topology, and
caching effects.Comment: 10 pages, 9 figures, journal pape
Optimized Quantification of Spin Relaxation Times in the Hybrid State
Purpose: The analysis of optimized spin ensemble trajectories for relaxometry
in the hybrid state.
Methods: First, we constructed visual representations to elucidate the
differential equation that governs spin dynamics in hybrid state. Subsequently,
numerical optimizations were performed to find spin ensemble trajectories that
minimize the Cram\'er-Rao bound for -encoding, -encoding, and their
weighted sum, respectively, followed by a comparison of the Cram\'er-Rao bounds
obtained with our optimized spin-trajectories, as well as Look-Locker and
multi-spin-echo methods. Finally, we experimentally tested our optimized spin
trajectories with in vivo scans of the human brain.
Results: After a nonrecurring inversion segment on the southern hemisphere of
the Bloch sphere, all optimized spin trajectories pursue repetitive loops on
the northern half of the sphere in which the beginning of the first and the end
of the last loop deviate from the others. The numerical results obtained in
this work align well with intuitive insights gleaned directly from the
governing equation. Our results suggest that hybrid-state sequences outperform
traditional methods. Moreover, hybrid-state sequences that balance - and
-encoding still result in near optimal signal-to-noise efficiency. Thus,
the second parameter can be encoded at virtually no extra cost.
Conclusion: We provide insights regarding the optimal encoding processes of
spin relaxation times in order to guide the design of robust and efficient
pulse sequences. We find that joint acquisitions of and in the
hybrid state are substantially more efficient than sequential encoding
techniques.Comment: 10 pages, 5 figure
Activity-guided isolation of natural products with immunosuppressive activity
The worldwide incidence of autoimmune diseases is rising, especially in industrialized countries. Apart from alleviating symptoms, the aim of any treatment is to regain a balance between tolerance and immunity. As T cells play a central role in both processes, the pathways leading to their activation are attractive targets for immunosuppressant drugs. The search for new inhibitors in recent years, however, was mostly focused on biologicals like monoclonal antibodies or fusion proteins. This improved the treatment of autoimmune conditions significantly, but administration and immunogenicity limit their application. Thus, there is a need for new small molecule immunosuppressant drugs with new modes of action.
To pursue new lead compounds, we mined the chemical space contained in a library of extracts from plants used in Traditional Chinese Medicine (TCM). This pre-selection was done to focus on plants used over a long period of time with some evidence for bioactivities. To identify extracts and compounds that inhibit the proliferation of activated primary T lymphocytes isolated from human blood, we used an in vitro assay. Through FACS analysis, the assay also allowed for the direct identification of cytotoxic or necrosis inducing effects.
We screened 435 extracts from plants used in TCM at a concentration of 30 µg/mL. From these, around 40 extracts showed T cell proliferation inhibition and 6 plants in total were selected for further investigations based on the absence of cytotoxicity, availability, batch to batch reproducibility, and a literature survey. Seven extracts from these plants were subjected to HPLC activity profiling, which allowed the identification of regions of activity in four of the extracts. The compounds in these active regions were the focus of subsequent isolation of compounds from these plant extracts. The work on two plants, Artemisia argyi and Toddalia asiatica, resulted in the publication of three peer reviewed publications. The work on two other extracts is still ongoing.
The first extract was an ethyl acetate extract from the aerial parts of A. argyi. From this extract, 18 compounds, including 5 new sesquiterpene lactones were isolated. A series of four isomeric sesquiterpene lactones, two diastereomeric seco-tanapartholides and two diastereomers of canin, showed activity at micromolar concentrations (IC50 values between 1.0 and 3.7 µM). Published data on the series of canin-diastereomers gave only unsatisfactory information on their identities and absolute configurations. Thus, their absolute configurations were determined independently using ECD and VCD. The relative configurations of seco-tanapartholides A and B were only known in part and interestingly, ECD gave almost enantiomeric spectra. Therefore, the absolute configuration was solved by VCD. Visual and computational methods were used for evaluation of the spectra. The knowledge of their absolute configurations can now be used as the basis for possible development as immunosuppressant lead compounds. These results are published in the Journal of Natural Products (Vol. 82, 2019).
Next, we investigated the mode of action of the isolated compounds and the ethyl acetate extract from A. argyi. To identify the affected transcription factors, reporter cell lines for AP-1, NFAT, and NF-κB were used. The target of the A. argyi extract and the tested sesquiterpene lactones was thereby found to be located upstream of NFAT and NF-κB. We further investigated the effects of both, the extract and the sesquiterpene lactones, on calcium signaling involved in the NFAT pathway. Although some of the compounds had an effect on calcium signaling, none of them, nor a combination of all, inhibited calcium influx into the cell or from the ER as effectively as the extract itself. These results were published in Frontiers in Pharmacology (Vol. 11, 2020).
The second extract we investigated in the course of this work was the MeOH extract from the roots of T. asiatica. Here, the alkaloid nitidine was identified as a highly active constituent with an IC50 value of 0.37 µM. Another, less active (IC50 6.72 µM), alkaloid was identified along with other inactive alkaloids, lignans and coumarins, some of them glycosylated. A combination of ECD, OR, GCMS analysis of hydrolyzed sugars, enantioselective HPLC analysis of hydrolyzed aglycones and NMR in the presence of the chiral shift reagent Eu(hbc)3 was used to identify the absolute configurations of these compounds. Three of the compounds were new natural products. The results are published in the Journal of Natural Products (Vol. 83, 2020).
From identifying several compounds with significant activity in inhibiting T cell proliferation, we found the CFSE assay to be useful for the identification of new lead compounds with relevant activities. As many of the natural products found did not have well described absolute configurations, we used a broad array of methods to fill this gap and publish the results for use by future researchers. The combination of ECD (as a sensitive method) with complementary techniques like VCD, chromatography of hydrolyzed compounds, or the use of shift reagents in NMR proved to be very effective. It enabled us to solve challenging cases like seco-tanapartholides A and B from A. argyi and the glycosylated coumarins from T. asiatica
An engineering analysis of a closed cycle plant growth module
The SOLGEM model is a numerical engineering model which solves the flow and energy balance equations for the air flowing through a growing environment, assuming quasi-steady state conditions within the system. SOLGEM provides a dynamic simulation of the controlled environment system in that the temperature and flow conditions of the growing environment are estimated on an hourly basis in response to the weather data and the plant growth parameters. The flow energy balance considers the incident solar flux; incoming air temperature, humidity, and flow rate; heat exchange with the roof and floor; and heat and moisture exchange with the plants. A plant transpiration subroutine was developed based plant growth research facility, intended for the study of bioregenerative life support theories. The results of a performance analysis of the plant growth module are given. The estimated energy requirements of the module components and the total energy are given
Hybrid-State Free Precession in Nuclear Magnetic Resonance
The dynamics of large spin-1/2 ensembles in the presence of a varying
magnetic field are commonly described by the Bloch equation. Most magnetic
field variations result in unintuitive spin dynamics, which are sensitive to
small deviations in the driving field. Although simplistic field variations can
produce robust dynamics, the captured information content is impoverished.
Here, we identify adiabaticity conditions that span a rich experiment design
space with tractable dynamics. These adiabaticity conditions trap the spin
dynamics in a one-dimensional subspace. Namely, the dynamics is captured by the
absolute value of the magnetization, which is in a transient state, while its
direction adiabatically follows the steady state. We define the hybrid state as
the co-existence of these two states and identify the polar angle as the
effective driving force of the spin dynamics. As an example, we optimize this
drive for robust and efficient quantification of spin relaxation times and
utilize it for magnetic resonance imaging of the human brain
Effect of Aqueous Ozone on the NF-κB System
Ozone has been proposed as an alternative oral antiseptic in dentistry, due to its antimicrobial power reported for gaseous and aqueous forms, the latter showing a high biocompatibility with mammalian cells. New therapeutic strategies for the treatment of periodontal disease and apical periodontitis should consider not only antibacterial effects, but also their influence on the host immune response. Therefore, our aim was to investigate the effect of aqueous ozone on the NF-κB system, a paradigm for inflammationassociated signaling/transcription. We showed that NF-κB activity in oral cells stimulated with TNF, and in periodontal ligament tissue from root surfaces of periodontally damaged teeth, was inhibited following incubation with ozonized medium. Under this treatment, IκBalpah proteolysis, cytokine expression, and κB-dependent transcription were prevented. Specific ozonized amino acids were shown to represent major inhibitory components of ozonized medium. In summary, our study establishes a condition under which aqueous ozone exerts inhibitory effects on the NF-κB system, suggesting that it has an antiinflammatory capacity
Huge quadratic magneto-optical Kerr effect and magnetization reversal in the CoFeSi Heusler compound
CoFeSi(100) films with L2 structure deposited onto MgO(100) were
studied exploiting both longitudinal (LMOKE) and quadratic (QMOKE)
magneto-optical Kerr effect. The films exhibit a huge QMOKE signal with a
maximum contribution of up to 30 mdeg, which is the largest QMOKE signal in
reflection that has been measured thus far. This large value is a fingerprint
of an exceptionally large spin-orbit coupling of second or higher order. The
CoFeSi(100) films exhibit a rather large coercivity of 350 and 70 Oe for
film thicknesses of 22 and 98 nm, respectively. Despite the fact that the films
are epitaxial, they do not provide an angular dependence of the anisotropy and
the remanence in excess of 1% and 2%, respectively
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