An efficient surrogate model for emulation and physics extraction of large eddy simulations

In the quest for advanced propulsion and power-generation systems, high-fidelity simulations are too computationally expensive to survey the desired design space, and a new design methodology is needed that combines engineering physics, computer simulations and statistical modeling. In this paper, we propose a new surrogate model that provides efficient prediction and uncertainty quantification of turbulent flows in swirl injectors with varying geometries, devices commonly used in many engineering applications. The novelty of the proposed method lies in the incorporation of known physical properties of the fluid flow as {simplifying assumptions} for the statistical model. In view of the massive simulation data at hand, which is on the order of hundreds of gigabytes, these assumptions allow for accurate flow predictions in around an hour of computation time. To contrast, existing flow emulators which forgo such simplications may require more computation time for training and prediction than is needed for conducting the simulation itself. Moreover, by accounting for coupling mechanisms between flow variables, the proposed model can jointly reduce prediction uncertainty and extract useful flow physics, which can then be used to guide further investigations.Comment: Submitted to JASA A&C

Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly

In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminator parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates

Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.

Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes 1 . Because OxPL are mostly the products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL2-4. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr-/- background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr-/- mice, Ldlr -/- E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis

Exclusive Production of Higgs Bosons in Hadron Colliders

We study the exclusive, double--diffractive production of the Standard Model Higgs particle in hadronic collisions at LHC and FNAL (upgraded) energies. Such a mechanism would provide an exceptionally clean signal for experimental detection in which the usual penalty for triggering on the rare decays of the Higgs could be avoided. In addition, because of the color singlet nature of the hard interaction, factorization is expected to be preserved, allowing the cross--section to be related to similar hard--diffractive events at HERA. Starting from a Fock state expansion in perturbative QCD, we obtain an estimate for the cross section in terms of the gluon structure functions squared of the colliding hadrons. Unfortunately, our estimates yield a production rate well below what is likely to be experimentally feasible.Comment: 17 pages, RevTeX file, four uufiled PostScript figures. UMPP #94-177. (Revised version. Some mistakenly missing Feynman diagrams are now added. Results do not change qualitatively. Paper reorganized.

Quantum dot imaging for embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Semiconductor quantum dots (QDs) hold increasing potential for cellular imaging both <it>in vitro </it>and <it>in vivo</it>. In this report, we aimed to evaluate <it>in vivo </it>multiplex imaging of mouse embryonic stem (ES) cells labeled with Qtracker delivered quantum dots (QDs).</p> <p>Results</p> <p>Murine embryonic stem (ES) cells were labeled with six different QDs using Qtracker. ES cell viability, proliferation, and differentiation were not adversely affected by QDs compared with non-labeled control cells (<it>P </it>= NS). Afterward, labeled ES cells were injected subcutaneously onto the backs of athymic nude mice. These labeled ES cells could be imaged with good contrast with one single excitation wavelength. With the same excitation wavelength, the signal intensity, defined as (total signal-background)/exposure time in millisecond was 11 ± 2 for cells labeled with QD 525, 12 ± 9 for QD 565, 176 ± 81 for QD 605, 176 ± 136 for QD 655, 167 ± 104 for QD 705, and 1,713 ± 482 for QD 800. Finally, we have shown that QD 800 offers greater fluorescent intensity than the other QDs tested.</p> <p>Conclusion</p> <p>In summary, this is the first demonstration of <it>in vivo </it>multiplex imaging of mouse ES cells labeled QDs. Upon further improvements, QDs will have a greater potential for tracking stem cells within deep tissues. These results provide a promising tool for imaging stem cell therapy non-invasively <it>in vivo</it>.</p

A Man with Labile Blood Pressure

Ronald Ma and colleagues discuss the differential diagnosis and management of a patient who presented with recurrent episodes of chest discomfort, palpitations, and labile blood pressure

Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions

Babesia microti, a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite. Furthermore, we found that polymorphism is restricted to a small number of genes, which are highly expressed during infection. In order to identify pathogen-encoded factors involved in host-parasite interactions, we screened a proteome array comprised of 174 B. microti proteins, including several predicted members of the parasite secretome. Using this immuno-proteomic approach we identified several novel antigens that trigger strong host immune responses during the onset of infection. The genomic and immunological data presented herein provide the first insights into the determinants of B. microti interaction with its mammalian hosts and their relevance for understanding the selective pressures acting on parasite evolution

Biological activity of Annona muricata seed extracts

A study was conducted to assess the biological activity of Annona muricata hexane, methanol and chloroform seed extracts. Both the hexane and methanol extracts showed moderate larvicidal activity against the Aedes aegypti larvae while the chloroform extract exhibited strong larvicidal property with an LC50 value of 0.9005µg/ml and an LC90 value of 6.1776µg/ml. Fraction 44b and 45b of the chloroform extracts were very toxic towards mosquito larvae with LC50 values of 0.7460 and 1.0402µg/ml, respectively. Identification of bioactive compounds revealed the presence of solamin, an acetogenin. From the cytotoxic assay against brine shrimp (Artemia salina), the methanol extract showed high toxicity with an LC50 value of 11.8823µg/ml. The results suggest potential application of the extracts in insecticidal formulations

Citostatsko i protuupalno djelovanje polisaharida biljke Ganoderma lucidum

In this study, polysaccharides were isolated from Ganoderma lucidum (Polyporaceae) and their antitumor and anti-inflammatory activities were investigated using in vivo models. Potential antitumor activity was shown by G. lucidum polysaccharides (GLP) against solid tumor induced by Ehrlich’s ascites carcinoma cells. GLP at 100 mg kg–1 body mass showed 80.8 and 77.6 % reduction in tumour volume and tumour mass, respectively, when administered 24 h after tumour implantation. Again, GLP at the same dose but when administered prior to tumour inoculation, showed 79.5 and 81.2 % inhibition of tumour volume and tumour mass, respectively. GLP showed significant dose-dependent activity in carrageenean-induced (acute) and formalin-induced (chronic) inflammation assays. At 100 mg kg–1, GLP exhibited 57.6 and 58.2 % inhibition in carrageenean-induced and formalin-induced assays, respectively.U radu je ispitano in vivo citostatsko i protuupalno djelovanje polisaharida (GLP) izoliranih iz biljke Ganoderma lucidum (Polyporaceae). Ispitivani polisaharidi pokazali su potencijalno antitumorsko djelovanje na Ehrlichov ascitesni tumor. GLP su u dozi od 100 mg kg1 tjelesne mase inhibirali volumen tumora za 80,8, a njegovu masu za 77,6 %, kada su primijenjeni 24 h nakon implantacije tumora. Ako se GLP daju u istoj dozi prije inokulacije tumora, inhibiraju volumen tumora za 79,5, a njegovu masu za 81,2 %. GLP pokazuju značajno, o dozi ovisno, protuupalno djelovanje u karagenan testu (akutna upala) i formalin testu (kronična upala). U dozi od 100 mg kg1, GLP inhibiraju upalne procese za 57,6 odnosno 58,2 % u testu s karagenanom, odnosno formalinom