Structural Control of Metamaterial Oscillator Strength and Electric Field Enhancement at Terahertz Frequencies

The design of artificial nonlinear materials requires control over the internal resonant charge densities and local electric field distributions. We present a MM design with a structurally controllable oscillator strength and local electric field enhancement at terahertz frequencies. The MM consists of a split ring resonator (SRR) array stacked above an array of nonresonant closed conducting rings. An in-plane, lateral shift of a half unit cell between the SRR and closed ring arrays results in a decrease of the MM oscillator strength by a factor of 4 and a 40% change in the amplitude of the resonant electric field enhancement in the SRR capacitive gap. We use terahertz time-domain spectroscopy and numerical simulations to confirm our results and we propose a qualitative inductive coupling model to explain the observed electromagnetic reponse.Comment: 11 pages, 5 figure

The Electric Word: Democracy, Technology, and the Arts (Book Review)

published or submitted for publicatio

Decoupling Crossover in Asymmetric Broadside Coupled Split Ring Resonators at Terahertz Frequencies

We investigate the electromagnetic response of asymmetric broadside coupled split ring resonators (ABC-SRRs) as a function of the relative in-plane displacement between the two component SRRs. The asymmetry is defined as the difference in the capacitive gap widths (\Delta g) between the two resonators comprising a coupled unit. We characterize the response of ABC-SRRs both numerically and experimentally via terahertz time-domain spectroscopy. As with symmetric BC-SRRs (\Delta g=0 \mu m), a large redshift in the LC resonance is observed with increasing displacement, resulting from changes in the capacitive and inductive coupling. However, for ABC-SRRs, in-plane shifting between the two resonators by more than 0.375Lo (Lo=SRR sidelength) results in a transition to a response with two resonant modes, associated with decoupling in the ABC-SRRs. For increasing \Delta g, the decoupling transition begins at the same relative shift (0.375Lo), though with an increase in the oscillator strength of the new mode. This strongly contrasts with symmetric BC-SRRs which present only one resonance for shifts up to 0.75Lo. Since all BC-SRRs are effectively asymmetric when placed on a substrate, an understanding of ABC-SRR behavior is essential for a complete understanding of BC-SRR based metamaterials

Wireless transfer of power by a 35-GHz metamaterial split-ring resonator rectenna

Wireless transfer of power via high frequency microwave radiation using a miniature split ring resonator rectenna is reported. RF power is converted into DC power by integrating a rectification circuit with the split ring resonator. The near-field behavior of the rectenna is investigated with microwave radiation in the frequency range between 20-40 GHz with a maximum power level of 17 dBm. The observed resonance peaks match those predicted by simulation. Polarization studies show the expected maximum in signal when the electric field is polarized along the edge of the split ring resonator with the gap and minimum for perpendicular orientation. The efficiency of the rectenna is on the order of 1% for a frequency of 37.2 GHz. By using a cascading array of 9 split ring resonators the output power was increased by a factor of 20

Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase-4 (PDE4)

PDE4 is one of eleven known cyclic nucleotide phosphodiesterase families and plays a pivotal role in mediating hydrolytic degradation of the important cyclic nucleotide second messenger, cyclic 3′5′ adenosine monophosphate (cAMP). PDE4 inhibitors are known to have anti-inflammatory properties, but their use in the clinic has been hampered by mechanism-associated side effects that limit maximally tolerated doses. In an attempt to initiate the development of better-tolerated PDE4 inhibitors we have surveyed existing approved drugs for PDE4-inhibitory activity. With this objective, we utilised a high-throughput computational approach that identified moexipril, a well tolerated and safe angiotensin-converting enzyme (ACE) inhibitor, as a PDE4 inhibitor. Experimentally we showed that moexipril and two structurally related analogues acted in the micro molar range to inhibit PDE4 activity. Employing a FRET-based biosensor constructed from the nucleotide binding domain of the type 1 exchange protein activated by cAMP, EPAC1, we demonstrated that moexipril markedly potentiated the ability of forskolin to increase intracellular cAMP levels. Finally, we demonstrated that the PDE4 inhibitory effect of moexipril is functionally able to induce phosphorylation of the Hsp20 by cAMP dependent protein kinase A. Our data suggest that moexipril is a bona fide PDE4 inhibitor that may provide the starting point for development of novel PDE4 inhibitors with an improved therapeutic window

Mycobacterial dihydrofolate reductase inhibitors identified using chemogenomic methods and in vitro validation.

The lack of success in target-based screening approaches to the discovery of antibacterial agents has led to reemergence of phenotypic screening as a successful approach of identifying bioactive, antibacterial compounds. A challenge though with this route is then to identify the molecular target(s) and mechanism of action of the hits. This target identification, or deorphanization step, is often essential in further optimization and validation studies. Direct experimental identification of the molecular target of a screening hit is often complex, precisely because the properties and specificity of the hit are not yet optimized against that target, and so many false positives are often obtained. An alternative is to use computational, predictive, approaches to hypothesize a mechanism of action, which can then be validated in a more directed and efficient manner. Specifically here we present experimental validation of an in silico prediction from a large-scale screen performed against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. The two potent anti-tubercular compounds studied in this case, belonging to the tetrahydro-1,3,5-triazin-2-amine (THT) family, were predicted and confirmed to be an inhibitor of dihydrofolate reductase (DHFR), a known essential Mtb gene, and already clinically validated as a drug target. Given the large number of similar screening data sets shared amongst the community, this in vitro validation of these target predictions gives weight to computational approaches to establish the mechanism of action (MoA) of novel screening hit

The Science of Pronominal Usage: He and It in Co-Reference to Inanimate Objects in Late Middle English Texts on Alchemy

This is the author's accepted manuscript. The published version can be found at http://dx.doi.org/10.1177/0075424210384225This article explores the variation between he and it in coreference to inanimate entities (such as mercury, sulfur, and salt). Using alchemical texts from the fifteenth century as material, the article demonstrates that there was much more variation in pronominal reference in this period than has previously been shown. Of the possible explanations suggested by previous research, the earlier grammatical gender system and transference from Latin do not seem to play a role, while pronoun clustering and pronominal reanalysis appear to influence the quantitative distribution. The scale of individuation used by Siemund and Stenroos to explain similar usage is shown not to be a straightforward predictor. Other factors such as personification and perceived similarities between animate and inanimate entities may affect the degree of perceived individuation. The choice of he over she seems to be influenced by pronominal reanalysis and straightforward personification in some cases. In other instances, it is speculated that the he usage reflects (stereotypical) gender conceptions in the Middle Ages

Helminth-Associated Systemic Immune Activation and HIV Co-receptor Expression: Response to Albendazole/Praziquantel Treatment

Background: It has been hypothesized that helminth infections increase HIV susceptibility by enhancing systemic immune activation and hence contribute to elevated HIV-1 transmission in sub-Saharan Africa. Objective: To study systemic immune activation and HIV-1 co-receptor expression in relation to different helminth infections and in response to helminth treatment. Methods: HIV-negative adults with (n = 189) or without (n = 57) different helminth infections, as diagnosed by Kato-Katz, were enrolled in Mbeya, Tanzania. Blinded to helminth infection status, T cell differentiation (CD45RO, CD27),activation (HLA-DR, CD38) and CCR5 expression was determined at baseline and 3 months after Albendazole/Praziquantel treatment. Plasma cytokine levels were compared using a cytometric bead array. Results: Trichuris and Ascaris infections were linked to increased frequencies of "activated'' CD4 and/or CD8 T cells (p< 0.05),whereas Hookworm infection was associated with a trend towards decreased HLA-DR+ CD8 T cell frequencies (p = 0.222). In Trichuris infected subjects, there was a linear correlation between HLA-DR+ CD4 T cell frequencies and the cytokines IL-1 beta and IL-10 (p<0.05). Helminth treatment with Albendazole and Praziquantel significantly decreased eosinophilia for S. mansoni and Hookworm infections (p<0.005) but not for Trichuris infection and only moderately modulated T cell activation. CCR5 surface density on memory CD4 T cells was increased by 1.2-fold during Trichuris infection (p-value: 0.053) and reduced after treatment (p = 0.003). Conclusions: Increased expression of T cell activation markers was associated with Trichuris and Ascaris infections with relatively little effect of helminth treatment