7,463 research outputs found
Investment Opportunities Forecasting: Extending the Grammar of a GP-based Tool
In this paper we present a new version of a GP financial forecasting tool, called EDDIE 8. The novelty of this version is that it allows the GP to search in the space of indicators, instead of using pre-specified ones. We compare EDDIE 8 with its predecessor, EDDIE 7, and find that new and improved solutions can be found. Analysis also shows that, on average, EDDIE 8's best tree performs better than the one of EDDIE 7. The above allows us to characterize EDDIE 8 as a valuable forecasting tool
Long-range surface plasmon polariton excitation at the quantum level
We provide the quantum mechanical description of the excitation of long-range
surface plasmon polaritons (LRSPPs) on thin metallic strips. The excitation
process consists of an attenuated-reflection setup, where efficient
photon-to-LRSPP wavepacket-transfer is shown to be achievable. For calculating
the coupling, we derive the first quantization of LRSPPs in the polaritonic
regime. We study quantum statistics during propagation and characterize the
performance of photon-to-LRSPP quantum state transfer for single-photons,
photon-number states and photonic coherent superposition states.Comment: 9 pages, 6 figures, RevTeX4; Accepted versio
Full tensor diffucion is not required to access the white-matter integrity in mouse contusion spinal cord injury
Effect of biochars pyrolyzed in N2 and CO2, and feedstock on microbial community in metal(loid)s contaminated soils
Little is known about the effects of applying amendments on soil for immobilizing metal(loid)s on the soil microbial community. Alterations in the microbial community were examined after incubation of treated contaminated soils. One soil was contaminated with Pb and As, a second soil with Cd and Zn. Red pepper stalk (RPS) and biochars produced from RPS in either N2 atmosphere (RPSN) or CO2 atmosphere (RPSC) were applied at a rate of 2.5% to the two soils and incubated for 30 days. Bacterial communities of control and treated soils were characterized by sequencing 16S rRNA genes using the Illumina MiSeq sequencing. In both soils, bacterial richness increased in the amended soils, though somewhat differently between the treatments. Evenness values decreased significantly, and the final overall diversities were reduced. The neutralization of pH, reduced available concentrations of Pb or Cd, and supplementation of available carbon and surface area could be possible factors affecting the community changes. Biochar amendments caused the soil bacterial communities to become more similar than those in the not amended soils. The bacterial community structures at the phylum and genus levels showed that amendment addition might restore the normal bacterial community of soils, and cause soil bacterial communities in contaminated soils to normalize and stabilize
Osteoprotegerin mediates tumor-promoting effects of Interleukin-1beta in breast cancer cells
__Background:__ It is widely recognized that inflammation promotes breast cancer invasion and metastasis. Given the complex nature of the breast tumor inflammatory microenvironment, much remains to be understood of the molecular mechanisms that govern these effects. We have previously shown that osteoprotegerin knockdown in breast cancer cells resulted in reduced invasion and metastasis. Here we present novel insight into the role of osteoprotegerin in inflammation-driven tumor progression in breast cancer by investigating the link between osteoprotegerin, macrophages and the potent pro-inflammatory cytokine Interleukin-1beta.
__Methods:__ We used human breast cancer cell lines to investigate the effects of Interleukin-1beta treatment on osteoprotegerin secretion as measured by ELISA. We analyzed public datasets containing human breast cancer genome-wide mRNA expression data to reveal a significant and positive correlation between osteoprotegerin mRNA expression and the mRNA expression of Interleukin-1beta and of monocyte chemoattractant protein CC-chemokine ligand 2. Osteoprotegerin, Interleukin-1beta and CC-chemokine ligand 2 mRNA levels were also examined by qPCR on cDNA from normal and cancerous human breast tissue. We determined the effect of Interleukin-1beta-producing macrophages on osteoprotegerin expression by co-culturing breast cancer cells and differentiated THP-1 macrophages. Immunohistochemistry was performed on human breast tumor tissue microarrays to assess macrophage infiltration and osteoprotegerin expression. To demonstrate that osteoprotegerin mediated functional effects of Interleukin-1beta we performed cell invasion studies with control and OPG siRNA knockdown on Interleukin-1beta-treated breast cancer cells.
__Results:__ We report that Interleukin-1beta induces osteoprotegerin secretion, independent of breast cancer subtype and basal osteoprotegerin levels. Co-culture of breast cancer cells with Interleukin-1beta-secreting macrophages resulted in a similar increase in osteoprotegerin secretion in breast cancer cells as Interleukin-1beta treatment. Macrophage infiltration correlates with osteoprotegerin secretion in human breast tumor tissue samples. We show that osteoprotegerin secretion is regulated by Interleukin-1beta in a p38- and p42/44-dependent manner. We also demonstrate that osteoprotegerin knockdown represses Interleukin-1beta expression, Interleukin-1beta-mediated breast cancer cell invasion and MMP3 expression.
__Conclusions:__ These data indicate a novel role for osteoprotegerin as a mediator of inflammation- promoted breast cancer progression
para-Selective C-H amidation of simple arenes with nitriles
A para-selective C-H amidation of simple arenes with nitriles has been developed. By increasing the amount of arenes, a further meta-selective C-H arylation of the produced amides occurred. Both steric and electronic effects are utilized to control the selectivity, resulting in only para-selective amidation products. The readily available nitriles as amidation reagents instead of amides makes the synthesis of N-arylamides more accessible
Selective conversion of CO into ethanol on Cu(511) surface reconstructed from Cu(pc): Operando studies by electrochemical scanning tunneling microscopy, mass spectrometry, quartz crystal nanobalance, and infrared spectroscopy
A polycrystalline copper, surface-terminated by a well-defined (511)-oriented facet, was electrochemically generated by a series of step-wise surface reconstruction and iterations of mild oxidative-reductive processes in 0.1 M KOH. The electrochemical reduction of CO on the resultant stepped surface was investigated by four surface-sensitive operando methodologies: electrochemical scanning tunneling microscopy (STM), electrochemical quartz crystal nanobalance (EQCN), differential electrochemical mass spectrometry (DEMS), and polarization-modulation infrared spectroscopy (PMIRS). The stepped surface catalyzed the facile conversion of CO into ethanol, the exclusive alcohol product at a low overpotential of −1.06 V (SHE) or − 0.3 V (RHE). The chemisorption of CO was found to be a necessary prelude to ethanol production; i.e. the surface coverages, rather than solution concentrations, of CO and its surface-bound intermediates primarily dictate the reaction rates (current densities). Contrary to the expected predominance of undercoordinated step-site reactivity over the coordination chemistry of vicinal surfaces, vibrational spectroscopic evidence reveals the involvement of terrace-bound CO adsorbates during the multi-atomic transformations associated with the production of ethanol
MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis
AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p
Three-dimensional photolithographic micropatterning: a novel tool to probe the complexities of cell migration
In order to independently study the numerous variables that influence cell movement, it will be
necessary to employ novel tools and materials that allow for exquisite control of the cellular
microenvironment. In this work, we have applied advanced 3D micropatterning technology, known as
two-photon laser scanning lithography (TP-LSL), to poly(ethylene glycol) (PEG) hydrogels modified with
bioactive peptides in order to fabricate precisely designed microenvironments to guide and
quantitatively investigate cell migration. Specifically, TP-LSL was used to fabricate cell adhesive PEGRGDS
micropatterns on the surface of non-degradable PEG-based hydrogels (2D) and in the interior of
proteolytically degradable PEG-based hydrogels (3D). HT1080 cell migration was guided down these
adhesive micropatterns in both 2D and 3D, as observed via time-lapse microscopy. Differences in cell
speed, cell persistence, and cell shape were observed based on variation of adhesive ligand, hydrogel
composition, and patterned area for both 2D and 3D migration. Results indicated that HT1080s migrate
faster and with lower persistence on 2D surfaces, while HT1080s migrating in 3D were smaller and
more elongated. Further, cell migration was shown to have a biphasic dependence on PEG-RGDS
concentration and cells moving within PEG-RGDS micropatterns were seen to move faster and with
more persistence over time. Importantly, the work presented here begins to elucidate the multiple
complex factors involved in cell migration, with typical confounding factors being independently
controlled. The development of this unique platform will allow researchers to probe how cells behave
within increasingly complex 3D microenvironments that begin to mimic specifically chosen aspects of
the in vivo landscape
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