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This investigation focused on identifying the impact of various steel fiber types on the mechanical response of an ultra-high performance concrete (UHPC) known as Cor-Tuf (CT). CT specimens were fabricated with four steel fiber types: hooked-end 3D 55/30 BG fibers, undulated NYCON type V fibers, straight brass coated OL 10mm fibers, and straight brass coated OL 6mm fibers. Fiber shape and size had a limited impact on quasi-static properties in compression but had a significant impact on quasi-static tensile properties and dynamic penetration resistance. The use of smaller fibers resulted in up to a 100 percent increase in component/test article tensile strength compared with their larger fiber size counterparts. However, the benefits offered by the smaller fibers primarily occurred prior to reaching the ultimate load carrying capacity. Once the ultimate strength was reached, larger fibers were more effective at bridging larger cracks. Smaller fibers provided improved penetration resistance, with reduced residual projectile velocities and loss of material from cratering and/or spallation. The overall goal of the study was to identify the relationships between fiber characteristics and the multi-strain rate response of UHPCs in order to better optimize fiber reinforcement for various loading conditions.

This paper summarizes the outcomes from the Turbulent Flow Simulation at the Exascale: Opportunities and Challenges Workshop, which was held 4-5 August 2015, and was sponsored by the U.S. Department of Energy Office of Advanced Scientific Computing Research. The workshop objective was to define and describe the challenges and opportunities that computing at the exascale will bring to turbulent-flow simulations in applied science and technology. The need for accurate simulation of turbulent flows is evident across the U.S. Department of Energy applied-science and engineering portfolios, including combustion, plasma physics, nuclear-reactor physics, wind energy, and atmospheric science. The workshop brought together experts in turbulent-flow simulation, computational mathematics, and high-performance computing. Building upon previous ASCR workshops on exascale computing, participants defined a research agenda and path forward that will enable scientists and engineers to continually leverage, engage, and direct advances in computational systems on the path to exascale computing.

The Polarized Electrons for Polarized Positrons experiment at the injector of the Continuous Electron Beam Accelerator Facility has demonstrated for the first time the efficient transfer of polarization from electrons to positrons produced by the polarized bremsstrahlung radiation induced by a polarized electron beam in a high-$Z$ target. Positron polarization up to 82\% have been measured for an initial electron beam momentum of 8.19~MeV/$c$, limited only by the electron beam polarization. This technique extends polarized positron capabilities from GeV to MeV electron beams, and opens access to polarized positron beam physics to a wide community., Comment: 5 pages, 4 figures

Under the new law, nurse practitioners expect that medical staffs will offer privileges without a requirement for supervision. Medical staffs have a responsibility to ensure quality of care and verify every member's competence, even as she or he acquires clinical experience. We believe that a model using progressive tiers of supervision, culminating in a level that allows practice directly accountable to OPPE and peer review, will meet nurse practitioners' expectations and medical staff responsibilities. Medical staff organizations and nurse practitioners have much to offer one another and need to develop processes that allow them to work together for the optimum benefit of their patients. The author wishes to thank Helen Brown, CRNP, for her assistance in the preparation of this article.

Abrasion is an important consideration for the potential release of nanoparticles during the service life of a nanotechnology. This SOP presents a general method for abrading a material using a rotating sample platform in contact with a weighted sandpaper fixture. Particles collected with this method are analyzed with a condensation particle counter (CPC) and a fast mobility particle sizer (FMPS), with additional particles collected on in-line filters for further analysis. The abrading process is carried out in a particle-free environment and released particles are moved by a defined airflow from the chamber to the collection/analysis apparatus. Particle release is monitored in real time by the CPC (10nm - 1 micrometer) and FMPS (32 particle size bins from 5-550 nm), and further characterization of filter-collected particles can be accomplished post-testing.

Cholangiocarcinoma is a highly lethal cancer with limited therapeutic options. Recent genomic analysis of cholangiocarcinoma has revealed the presence of fibroblast growth factor receptor 2 (FGFR2) fusion proteins in up to 13% of intrahepatic cholangiocarcinoma (iCCA). FGFR fusions have been identified as a novel oncogenic and druggable target in a number of cancers. In this study, we established a novel cholangiocarcinoma patient derived xenograft (PDX) mouse model bearing an FGFR2-CCDC6 fusion protein from a metastatic lung nodule of an iCCA patient. Using this PDX model, we confirmed the ability of the FGFR inhibitors, ponatinib, dovitinib and BGJ398, to modulate FGFR signaling, inhibit cell proliferation and induce cell apoptosis in cholangiocarcinoma tumors harboring FGFR2 fusions. In addition, BGJ398 appeared to be superior in potency to ponatinib and dovitinib in this model. Our findings provide a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions.

This research examined the evolving microstructure of quasi-static and dynamically loaded fully annealed metastable 301 austenitic stainless steel (SS). Experiments were performed to an interrupted strain value of 20% and to failure using a tension Kolsky bar (1000/s) and an electromechanical load frame (0.001/s). Electron Backscatter Diffraction (EBSD) identified the microstructural evolution from the as-received condition to the 20% strain level for the high and low rate interrupted samples. This material achieved over 60% elongation to failure with increasing strength as strain rate increased, as expected. Fractography analysis using SEM showed particles in the microstructure and a ductile failure mode. The 301 SS exhibited a greater amount of phase transformation from parent austenite to α’-martensite at the dynamic strain rate when compared to the quasi-static strain rate during the interrupted experiments. This result is indicative of the increased propensity for austenite to α’-martensite phase transformations at the high strain rate.

A glass–ceramic coating made by fusing dicalcium silicate and tricalcium silicate to the surface of glass-enameled steel has been successfully used to increase the bond between reinforcing steel and concrete and provide corrosion protection for the steel. A very strong interface that consists of hydrated cement and enameled glass over the top of a second strong interface between the enameled glass and the surface of the steel results from the outer layer of water-reactive silicates hydrating on contact with fresh concrete. Currently the mechanical characteristics (hardness, elastic modulus and strain-rate sensitivity), micromorphology, and the variation in interface chemical composition are being examined. Preliminary results indicate that the more gradual transition between the mechanical properties of the steel and the paste combined with improved integration between the coating and cement hydration products in the paste results in the increased bond strength observed in macroscale tests. Results from this study to characterize the developed coating are being used to engineer new optimized enamels for this unique application.

Monitoring the lunar surface for impacts is a highly rewarding approach to study small asteroids and large meteoroids encountering the Earth–Moon System. The various effects of meteoroids impacting the Moon are described and results from different detection and study techniques are compared. While the traditional statistics of impact craters allow us to determine the cumulative meteoroid flux on the lunar surface, the recent successful identification of fresh craters in orbital imagery has the potential to directly measure the cratering rate of today. Time-resolved recordings, e.g., seismic data of impacts and impact flash detections clearly demonstrate variations of the impact flux during the lunar day. From the temporal/spatial distribution of impact events, constraints can be obtained on the meteoroid approach trajectories and velocities. The current monitoring allows us to identify temporal clustering of impacts and to study the different meteoroid showers encountering the Earth–Moon system. Though observational biases and deficiencies in our knowledge of the scaling laws are severe, there appears to be an order-of-magnitude agreement in the observed flux within the error limits. Selenographic asymmetries in the impact flux (e.g., for equatorial vs. polar areas) have been predicted. An excess of impacts on the lunar leading hemisphere can be demonstrated in current data. We expect that future missions will allow simultaneous detections of seismic events and impact flashes. The known locations and times of the flashes will allow us to constrain the seismic solutions. While the numbers of flash detections are still limited, coordinated world-wide observations hold great potential for exploiting this observation technique. The potential for identification of fresh craters in high-resolution orbital image data has just barely been tapped, but should improve significantly with the LRO extended mission.

Recent interest in bio-inspired materials has led to the development of techniques that can be used to synthesize hierarchical structures with controlled morphology and mineralogy. One such technique investigated in this study consists of the use of electromigration and electrodeposition techniques to deposit mineral phases with controlled morphology and mineralogy by infilling a predefined porous templates. Here, the utility of precipitating various polymorphs of calcium carbonate in three-dimensional templates is demonstrated. Applied potentials and times were varied while scanning electron microscopy and X-ray diffraction were used to determine polymorph formed and its morphology. It was found that higher applied potentials and shorter operating times resulted in the formation of metastable polymorphs of calcium carbonate (e.g., vaterite) that infilled the porous media. Results provide insights for developing bio-inspired composite materials for various structural and medical applications, such as synthetic bone.

Misfit-layered Ca3Co4O9 crystals were grown and characterized via XRD, SEM, and photo-emission spectroscopy (PES). The evolution of the intensity at the Fermi level (EF) with varying oxygen content was studied by PES. Oxygen species were successfully introduced and removed through O+ and H+ microwave-plasma (2.45 GHz, 2–5 mbar) treatments, respectively. A 5 min O+ plasma exposure was observed to result into a drastic enhancement in the EF intensity, demonstrating the influence of oxygen content to the charge carrier population in layered cobalt-oxide materials.

Mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, have been reported in gliomas, myeloid leukemias, chondrosarcomas, and thyroid cancer. We discovered IDH1 and IDH2 mutations in 34 of 326 (10%) intrahepatic cholangiocarcinomas. Tumor with mutations in IDH1 or IDH2 had lower 5-hydroxymethylcytosine (5hmC) and higher 5-methylcytosine (5mC) levels, as well as increased dimethylation of histone H3K79. Mutations in IDH1 or IDH2 were associated with longer overall survival (p = 0.028) and were independently associated with a longer time to tumor recurrence after intrahepatic cholangiocarcinoma resection in multivariate analysis (p = 0.021). IDH1 and IDH2 mutations are significantly associated with increased levels of p53 in intrahepatic cholangiocarcinomas, but no mutations in the p53 gene were found, suggesting that mutations in IDH1 and IDH2 may cause a stress that leads to p53 activation. We identified 2,309 genes that were significantly hypermethylated in 19 cholangiocarcinomas with mutations in IDH1 or IDH2, compared with cholangiocarcinomas without these mutations. Hypermethylated CpG sites were significantly enriched in CpG shores and upstream of transcription start sites, suggesting a global regulation of transcriptional potential. Half of the hypermethylated genes overlapped with DNA hypermethylation in IDH1-mutant gliobastomas, suggesting the existence of a common set of genes whose expression may be affected by mutations in IDH1 or IDH2 in different types of tumors.

This paper presents the results of a study examining the Cl − induced corrosion resistance of austenitic, duplex, and martensitic high-strength stainless steels (HSSSs) and a pearlitic prestressing steel using cyclic potentiodynamic polarization (CPP) techniques in simulated alkaline and carbonated concrete solutions. CPP testing found that in alkaline solutions, all HSSSs showed high corrosion resistance at Cl − concentrations from zero to 0.25 M. When exposed to carbonated solutions, corrosion resistance was reduced and only duplex grades S32205 and S32304 exhibited high corrosion resistance. A strong correlation between microstructural defects (e.g., strain-induced martensite) and corrosion damage was observed in the cold-drawn HSSSs.

A simple fabrication of ZnO-nanowire-based device and their implementation as a pH sensor, temperature sensor, and photo detector is reported. The presented multifunctional ZnO multiple-nanowire sensor platform contains a Au finger structure, which is realized by conventional photolithography on a SiO2 substrate. The nanowires are grown using thermal chemical vapor deposition. In order to detect the physical signals, changes in electrical signals were measured (conductance and current). For temperature sensing, the current behavior from 90 to 380 K under vacuum conditions exhibit a tunneling behavior between spaced nanowires. For photo sensing, the current response between the “on” and “off” states of light was measured when exposed to different wavelengths ranging from UV to visible light. Finally, for pH sensing the conductance was measured between a pH of 5 and 8.5. The ZnO nanowires were protected from chemical attacks by a thin layer of C4F8-plasma-based coating.

Elevated serum immunoglobulin G4 (sIgG4) is a feature of autoimmune pancreatitis (AIP) and IgG4-associated cholangitis (IAC); a >2-fold increase in sIgG4 is considered highly specific for these disorders. Many patients with IAC present with biliary strictures and obstructive jaundice, making cholangiocarcinoma (CCA) an important differential diagnosis. We determined the value of sIgG4 in distinguishing IAC from CCA. sIgG4 levels were measured in a test cohort of 126 CCA and 50 IAC patients. The results were confirmed in a validation cohort of 161 CCA and 47 IAC patients. Of the 126 CCA patients in the test cohort, 17 (13.5%) had elevated sIgG4 (>140 mg/dL) and four (3.2%) had a >2-fold (>280 mg/dL) increase. Primary sclerosing cholangitis (PSC) was present in 31/126 CCA patients, of whom seven (22.6%) had elevated sIgG4 and two (6.5%) had a >2-fold elevation. Of the 50 IAC patients, 39 (78.0%) had elevated sIgG4 and 25 (50.0%) had a >2-fold increase. The results in the validation cohort were consistent with those of the test cohort. Conclusion: Although elevated sIgG4 levels are characteristic of IAC, some patients with CCA, particularly with PSC, have elevated sIgG4 levels, including a small percentage with a more than a 2-fold increase in sIgG4. Therefore, sIgG4 elevation alone does not exclude the diagnosis of CCA. Depending on the prevalence of the two diagnoses, the use of a 2-fold cutoff for sIgG4 may not reliably distinguish IAC from CCA. At a cutoff of 4 times the upper limit of normal, sIgG4 is 100% specific for IAC. (HEPATOLOGY 2011;)

The influence of boundary roughness characteristics on the rate of dissipation in a viscous fluid is analyzed using shape calculus from the theory of optimal control of systems governed by partial differential equations. To study the mapping $\mathscr{D}$ from surface roughness topography to the dissipation rate of a Navier–Stokes flow, expressions for the shape gradient and Hessian are determined using the velocity method. In the case of Couette and Poiseuille flows, a flat boundary is a local minimum of the dissipation rate functional. Thus, for small roughness heights the behavior of $\mathscr{D}$ is governed by the flat-wall shape Hessian operator, whose eigenfunctions are shown to be the Fourier modes. For Stokes flow, the shape Hessian is determined analytically and its eigenvalues are shown to grow linearly with the wavenumber of the shape perturbation. For Navier–Stokes flow, the shape Hessian is computed numerically, and the ratio of its eigenvalues to those of a Stokes flow depend only on the Re...

The potential for binary and ternary blends of metakaolin, with two differing particle size distributions, and Class C fly ash to mitigate alkali-silica reactions (ASR) with a highly reactive fine aggregate were evaluated using accelerated mortar bar test (AMBT) and concrete prism test (CPT) methods. Binary blends of metakaolin or Class C fly ash reduced expansion by 55–90% and 25–37% compared to the control, respectively. When incorporating metakaolin with a lower mean particle size, binary blends showed a greater reduction in expansion compared with Class C fly ash. Ternary blends of metakaolin and Class C fly ash resulted in a marginally higher expansion than binary blends incorporating the same amount of metakaolin. Correlation between AMBT and CPT results was good at high levels of expansion but poor for those compositions producing expansions near the acceptable limits corresponding to increased addition rates of metakaolin and/or Class C fly ash.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide (1). Because of frequent de novo and acquired resistance of HCCs to chemotherapy, there are limited options for therapy of HCC (2, 3). There is therefore an urgent need for improved therapy of HCC. Consequently there is strong interest in identifying novel molecular targets for therapy of advanced HCC. The role of the extracellular heparan sulphate 6-O-endosulphatases, sulfatase 1 (SULF1) and sulfatase 2 (SULF2) in human carcinogenesis has not been completely elucidated (4, 5). SULF1 has been shown to function as a tumour suppressor in HCC, head and neck cancer, ovarian cancer and pancreatic cancer (5–10). SULF1 and SULF2 have also been reported to inhibit tumour growth in multiple myeloma (11). In contrast, SULF2 is upregulated in breast cancer and functions as an oncogene in HCC, pancreas cancer, lung cancer and chronic lymphocytic leukemia (12–16). Gene expression microarray analysis of 139 pairs of HCC tumour and adjacent benign tissue showed upregulation of SULF2 in 57% of HCCs (13). The 5-year survival rate for patients with HCCs with upregulated SULF2 was significantly worse than for those with down-regulated SULF2. Patients with upregulated SULF2 also had earlier recurrence of HCC after surgery. Immunohistochemical analysis of cell proliferation and apoptosis was performed in 30 of the HCCs (13). Tumours were classified into subclass A (poor prognosis) or subclass B (good prognosis) based on the prior gene expression profiling study by Lee et al. (17). Subclass A tumours were more frequent in the high SULF2 group (13 of 14 tumours) and less frequent in the low SULF2 group (two of 16 tumours; P=0.00001). HCCs with high SULF2 expression also had a significantly higher Ki-67 proliferation index (P= 0.007) and a significantly lower apoptosis index (P = 0.0001) than those with low SULF2 expression. SULF2 expression therefore correlated with increased proliferation and decreased apoptosis (13). In experiments to validate these results, we showed that SULF2 promoted proliferation and migration of HCC cells in vitro (13, 18). Mechanistically, SULF2 upregulated cell surface glypican 3 and promoted FGF signalling. Expression of SULF2 increased phosphorylation of Erk and Akt (13). SULF2 expression also increased phosphorylation of the anti-apoptotic Akt substrate GSK3β and stimulated Wnt/β-catenin signalling(19). Other investigators have also demonstrated that SULF2 promotes signalling by receptor tyrosine kinase ligands, Wnts and other growth factors (14, 20, 21). In terms of associations with other known pro-apoptotic molecules, SULF2 has been shown to be a transcriptional target of p53 in colon cancer, lung cancer, ovarian cancer and HCC cells, but the direct or indirect effects of SULF2 on apoptosis and apoptosis-related pathways in HCC have not been reported (22, 23). ERK, PI3K/Akt and JNK pathway inhibitors and histone deacetylase (HDAC) inhibitors induce apoptosis and are currently in clinical trials for cancer therapy (24–26). We studied the expression of SULF2 in HCCs and determined the role of SULF2 in modulating apoptosis induced by these kinase and HDAC inhibitors in HCC cells. The questions addressed in this study were: Is SULF2 mRNA expression correlated to protein expression in HCCs? Do changes in SULF2 expression affect cell viability, caspase activation and induction of apoptosis of HCC cells by ERK, PI3K, JNK or HDAC inhibitors? Does knockdown of SULF2 inactivate the Akt pathway? Does knockdown of SULF2 inhibit cell cycle progression as measured by cyclin D1 expression? Does SULF2 mediate its effects by regulating apoptosis-related Bcl-2, Bcl-XL and BAD protein expression?

We investigate computationally the role of Stone-Wales (SW) defects on the interfacial interactions among graphene, carbon nanotubes (CNTs), and Nylon 6 using density functional theory (DFT) and the empirical force-field. Our first-principles DFT calculations were performed using the Quantum ESPRESSO electronic structure code with the highly accurate van der Waals functional (vdW-DF2). Both pristine and SW-defected carbon nanomaterials were investigated. The computed results show that the presence of SW defects on CNTs weakens the CNT-graphene interactions. Our result that CNT-graphene interaction is much stronger than CNT-CNT interaction indicates that graphene would be able to promote the dispersion of CNTs in the polymer matrix. Our results demonstrate that carbon nanomaterials form stable complexes with Nylon 6 and that the van der Waals interactions, as revealed by the electronic charge density difference maps, play a key stabilizing role on the interfacial interactions among graphene, CNTs, and Nylon 6. Using the density of states calculations, we observed that the bandgaps of graphene and CNTs were not significantly modified due to their interactions with Nylon 6. The Young's moduli of complexes were found to be the averages of the moduli of their individual constituents.

Heparan sulfate proteoglycans (HSPGs) act as coreceptors or storage sites for growth factors and cytokines such as fibroblast growth factor and Wnts. Glypican 3 (GPC3) is the most highly expressed HSPG in hepatocellular carcinoma (HCC). Sulfatase 2 (SULF2), an enzyme with 6-O-desulfatase activity on HSPGs, is up-regulated in 60% of primary HCCs and is associated with a worse prognosis. We have previously shown that the oncogenic effect of SULF2 in HCC may be mediated in part through up-regulation of GPC3. Here we demonstrate that GPC3 stimulates the Wnt/β-catenin pathway and mediates the oncogenic function of SULF2 in HCC. Wnt signaling in vitro and in vivo was assessed in SULF2-negative Hep3B HCC cells transfected with SULF2 and in SULF2-expressing Huh7 cells transfected with short hairpin RNA targeting SULF2. The interaction between GPC3, SULF2, and Wnt3a was assessed by coimmunoprecipitation and flow cytometry. β-catenin–dependent transcriptional activity was assessed with the TOPFLASH (T cell factor reporter plasmid) luciferase assay. In HCC cells, SULF2 increased cell surface GPC3 and Wnt3a expression, stabilized β-catenin, and activated T cell factor transcription factor activity and expression of the Wnt/β-catenin target gene cyclin D1. Opposite effects were observed in SULF2-knockdown models. In vivo, nude mouse xenografts established from SULF2-transfected Hep3B cells showed enhanced GPC3, Wnt3a, and β-catenin levels. Conclusion: Together, these findings identify a novel mechanism mediating the oncogenic function of SULF2 in HCC that includes GPC3-mediated activation of Wnt signaling via the Wnt3a/glycogen synthase kinase 3 beta axis. (HEPATOLOGY 2010;)

Left ventricular assist devices (LVADs) are continuous flow pumps that are employed in patients with severe heart failure. Although their emergence has significantly improved therapeutic options for patients with heart failure, detailed studies of the impact of LVADs on hemodynamics are notably lacking. To this end we initiate a computational study of the Jarvik 2000 LVAD model employing isogeometric fluid–structure interaction analysis. We focus on a patient-specific configuration in which the LVAD is implanted in the descending thoracic aorta. We perform computations for three pump settings and report our observations for several quantities of hemodynamic interest. It should be noted that this paper presents the first three-dimensional, patient-specific fluid–structure interaction simulation of LVADs.

Background/Aims The FRA16D fragile site gene WWOX is a tumor suppressor that participates in p53-mediated apoptosis. The c-jun N-terminal kinase JNK1 interacts with WWOX and inhibits apoptosis. We investigated the function of WWOX in human hepatocellular carcinoma (HCC) and the effect of JNK inhibition on WWOX-mediated apoptosis. Methods Allelic imbalance on chromosome 16 was analyzed in 73 HCCs using 53 microsatellite markers. WWOX mRNA in HCC cell lines and primary HCCs was measured by real-time RT-PCR. Effects of WWOX on proliferation and apoptosis and the interaction between WWOX and JNK inhibition were examined. Results Loss on chromosome 16 occurred in 34 of 73 HCCs. Of 11 HCC cell lines, 2 had low, 7 intermediate, and 2 had high WWOX mRNA. Of 51 primary tumors, 23 had low WWOX mRNA. Forced expression of WWOX in SNU387 cells decreased FGF2-mediated proliferation and enhanced apoptosis induced by staurosporine and the JNK inhibitor SP600129. Conversely, knockdown of WWOX in SNU449 cells using shRNA targeting WWOX increased proliferation and resistance to SP600129-induced apoptosis. Conclusions WWOX induces apoptosis and inhibits human HCC cell growth through a mechanism enhanced by JNK inhibition.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death world-wide. 1 Risk factors for HCC include chronic hepatitis and cirrhosis secondary to hepatitis B virus or hepatitis C virus infection, alcoholic cirrhosis, nonalcoholic steatohepatitis, hemochromatosis, alpha-1-antitrypsin deficiency, and dietary aflatoxin exposure.2 Survival of patients diagnosed with advanced HCC is dismal. Only a small proportion of HCCs are detected at an early stage at which potentially curative therapies are feasible. Because of frequent de novo and acquired resistance of HCCs to chemotherapy, standard chemotherapeutic agents are not effective against HCC.3 Recent trials have proven the efficacy of the multi-targeting Raf and receptor tyrosine kinase inhibitor sorafenib in advanced HCC.4 Therefore, there is considerable interest in identifying additional novel gene targets for therapy against HCC. The recently identified human sulfatase 2 (SULF2) gene at chromosome 20q13 encodes a protein with heparin-degrading endosulfatase activity.5 Cell-surface signaling by several heparin-binding growth factors, including fibroblast growth factor (FGF), heparin-binding epidermal growth factor, hepatocyte growth factor, and vascular endothelial growth factor, requires the binding of both the growth factor and its cognate cell-surface receptor tyrosine kinase to sulfated heparan sulfate glycosaminoglycans. 6,7 For these growth factors, sulfation of particular saccharide moieties of heparan sulfate proteoglycans (HSPGs) is required for growth factor signaling. It has been shown that desulfation of HSPGs by the related protein, sulfatase 1 (SULF1), inhibits binding of the growth factor to its receptor, abrogates growth factor signaling, and has a tumor suppressor effect.8–15 In contrast to SULF1, it has been reported that SULF2 messenger RNA (mRNA) is up-regulated in human breast cancers,16 and suppression of SULF2 expression decreases tumorigenesis of pancreatic cancer cell lines.17 Thus, although SULF2 and SULF1 share the same HSPG substrate, it appears that they have different functional effects.18 This model is supported by recent evidence that human SULF2 mobilizes growth factors and chemokines from heparin and consequently facilitates growth factor signaling. 19 Because our initial studies suggested that SULF2 has an oncogenic effect, we hypothesized that SULF2 increases HCC bcell growth by release of growth factors from cell surface or extracellular matrix HSPG storage sites, thereby enhancing binding of FGF2 and other receptor tyrosine kinase ligands to their corresponding receptors and leading to cell growth. Therefore, we studied the expression of SULF2 in HCCs and examined the role of SULF2 in modulating growth of HCCs. Glypicans are a family of HSPGs that are bound to the cell surface by a lipid glycosyl-phosphatidylinositol anchor. Glypican 3 (GPC3) is markedly overexpressed in a high proportion of HCCs and promotes the growth of HCCs.20–22 We therefore also investigated the potential interactions between SULF2, FGF2 signaling, and GPC3. The following questions were addressed: Is SULF2 expression increased in HCC? Does SULF2 expression affect growth and migration of HCC cells? Does SULF2 affect FGF2 binding to the cell surface? Does SULF2 modulate expression of GPC3? Does SULF2 predict prognosis of HCC patients?

The research on bioceramics during the last decades has proved that the bioactivity of inorganic bone grafts depends fundamentally on an optimal combination of chemistry and structural porosity. This study presents a comparison of a resorbable monophasic hydroxyapatite (HA) and several newly developed resorbable biphasic hydroxyapatite – s-tricalcium phosphate (HA/TCP) composites both derived from naturally grown red marine algae with respect to the phase composition, microstructure and porosity. The highly porous three dimensional mineral scaffold of the native alga is maintained in the final products all investigated materials and possesses a pronounced interconnecting microporous structure. There are generally high values of specific porosity calculated for all tested materials: 1.07 cm3/g for pure phycogenic HA and between 0.65 cm3/g and 1.04 cm3/g for phycogenic biphasic HA/TCP composites with various HA/TCP ratios. The ultrastructure of the phycogenic HA/TCP composites changes significantly with the building and the increase of the s-TCP phase due to the bigger polyedric s-TCP crystals compared to the finer polycrystalline HA. Despite these structural changes the interconnected porous scaffold is kept throughout the production process. In all investigated materials the porosity is mainly based on pores with pore sizes between 1 and 10 μm in diameter, which is given by the structure of the natural alga. The specific chemistry combined with the structural porosity is decisive for the high in-vivo bioactivity of the studied materials. Chemie, Ultrastruktur und Porositat eines monophasischen sowie einiger biphasischen aus Meeresalgen gewonnenen Knochenaufbaumaterialien Die Forschung an biokeramischen Materialien wahrend der letzten Jahrzehnte hat ergeben, dass die Bioaktivitat anorganischer Knochenersatzmaterialien grundsatzlich auf einer optimalen Kombination chemischer Parameter und Porositat basiert. Die vorliegende Studie prasentiert einen Vergleich zwischen einem monophasischen resorbierbaren Hydroxylapatit (HA) und mehreren neu entwickelten resorbierbaren biphasischen Hydroxylapatit – s-Trikalziumphosphat (HA/TCP) Materialien, die aus naturlich gewachsenen Rotalgen gewonnen wurden, bezuglich Phasenzusammensetzung, Mikrostruktur und Porositat. Das dreidimensionale mineralische Stutzgewebe der naturlichen Alge besitzt eine ausgepragt interkonnektierende Mikroporositat und wird bis zu den Endprodukten aller untersuchten Materialien beibehalten. Die durchgefuhrten Analysen zeigen generell hohe Werte im Hinblick auf die spezifische Porositat: reiner phykogener HA 1.07 cm3/g sowie die phycogenen biphasischen HA/TCP Materialien mit unterschiedlichen HA/TCP Verhaltnissen zwischen 0.65 cm3/g und 1.04 cm3/g. Die Ultrastruktur der phykogenen biphasischen HA/TCP Materialien andert sich signifikant mit der Bildung und der Konzentrationssteigerung der s-TCP Phase auf Grund der groseren polyedrischen s-TCP Kristalle im Vergleich zu dem feinen polykristallinen HA. Trotz dieser strukturellen Anderungen bleibt die interkonnektierend porose Stutzstruktur wahrend des Produktionsprozesses erhalten. Die Porositat aller untersuchten Materialien basiert vor allem auf Poren mit einem Durchmesser zwischen 1 und 10 μm, was durch den Habitus der naturlichen Alge vorgegeben ist. Der spezifische Chemismus in Verbindung mit der porosen Struktur ist verantwortlich fur die hohe in-vivo Bioaktivitat der untersuchten Materialien.

This paper uses direct numerical simulations (DNS) of turbulent flow in a channel at $$ \operatorname{Re} _{\tau } = 950 $$ (Del Alamo, Jimenez, Zandonade, Moser J Fluid Mech 500:135–144, 2004) to provide a picture of the turbulent structures making large contributions to the Reynolds shear stress. Considerable work of this type has been done for the viscous wall region at smaller $$ \operatorname{Re} _{\tau } $$ , for which a log-layer does not exist. Recent PIV measurements of turbulent velocity fluctuations in a plane parallel to the direction of flow have emphasized the dominant contribution of large scale structures in the outer flow. This prompted Hanratty and Papavassiliou (The role of wall vortices in producing turbulence. In: Panton, R.L. (ed) Self-sustaining Mechanism of Wall Turbulence. Computational Mechanics Publications, Southampton, pp. 83–108, 1997) to use DNS at $$ \operatorname{Re} _{\tau } = 150,\;300 $$ to examine these structures in a plane perpendicular to the direction of flow. They identified plumes which extend from the wall to the center of a channel. The data at $$ \operatorname{Re} _{\tau } = 950 $$ are used to explore these results further, to examine the structure of the log-layer, and to test present notions about the viscous wall layer.

The governing equations for the two-point correlations of the turbulent fluctuating velocity in the temporally evolving wake were analysed to determine whether they could have equilibrium similarity solutions. It was found that these equations could have such solutions for a finite-Reynolds-number wake, where the two-point velocity correlations could be written as a product of a time-dependent scale and a function dependent only on similarity variables. It is therefore possible to collapse the two-point measures of all the scales of motions in the temporally evolving wake using a single set of similarity variables. As in an earlier single-point analysis, it was found that the governing equations for the equilibrium similarity solutions could not be reduced to a form that was independent of a growth-rate dependent parameter. Thus, there is not a single ‘universal’ solution that describes the state of the large-scale structures, so that the large-scale structures in the far field may depend on how the flow is generated.The predictions of the similarity analysis were compared to the data from two direct numerical simulations of the temporally evolving wakes examined previously. It was found that the two-point velocity spectra of these temporally evolving wakes collapsed reasonably well over the entire range of scales when they were scaled in the manner deduced from the equilibrium similarity analysis. Thus, actual flows do seem to evolve in a manner consistent with the equilibrium similarity solutions.

The low regression rates of classic hybrid rocket fuels lead to large internal ports that limit potential applications. This experimental study investigated the increase in regression rate that results from adding a solid oxidizer and a catalyst to a hybrid fuel grain. The configuration is named a "mixed hybrid" hybrid to signify solid oxidizer and catalyst in the grain. A design of experiments approach guided fuel formulation to systematically control levels of ammonium perehlorate from 25% to 30%, ferric oxide from 0 to 5%, and hydroxyl-terminated polybutadiene from 70% to 75%. The 1.5-in. diam. port, 12-in. long center perforated grains were burned with gaseous oxygen at pressure levels from 150 to 550 psig and port flux levels from 0.1 to 0.4 lbm/s-in. 2 . The results show that the mixed hybrid propellants burn as a function of both pressure and mass flux. A grain formulation having 27.5 % ammonium perchlorate and 2.5% ferric oxide provided the maximum burning rate augmentation (447%) among the formulations tested.

We present a hierarchical Bayesian framework for the selection of force fields in molecular dynamics (MD) simulations. The framework associates the variability of the optimal parameters of the MD potentials under different environmental conditions with the corresponding variability in experimental data. The high computational cost associated with the hierarchical Bayesian framework is reduced by orders of magnitude through a parallelized Transitional Markov Chain Monte Carlo method combined with the Laplace Asymptotic Approximation. The suitability of the hierarchical approach is demonstrated by performing MD simulations with prescribed parameters to obtain data for transport coefficients under different conditions, which are then used to infer and evaluate the parameters of the MD model. We demonstrate the selection of MD models based on experimental data and verify that the hierarchical model can accurately quantify the uncertainty across experiments; improve the posterior probability density function estimation of the parameters, thus, improve predictions on future experiments; identify the most plausible force field to describe the underlying structure of a given dataset. The framework and associated software are applicable to a wide range of nanoscale simulations associated with experimental data with a hierarchical structure.

For decades, researchers gradually unveiled the fascinating design principles that give biomaterials extraordinary properties and functionality. The US Army Engineer Research and Development Center (ERDC) is incorporating these design principles to develop hierarchical materials for structural applications. Electrophoretic deposition is one method being explored to create the hierarchical structures. This research details the synthesis of hierarchical nanocomposites composed of calcium carbonate by using electrotransport and electrophoretic deposition to migrate calcium and carbonate ions through a polymer matrix. This process allows better control of the crystal form, size, and location in the polymer matrix, allowing for fabrication of composite materials with optimized mechanical properties for various loading conditions. Other research efforts focused on the use of hydrothermal processing techniques to promote the oriented recrystallization of calcium carbonate. These techniques are being used successfully to fabricate composites for characterization and mechanical testing.

The work presented here is a study of a digital method for determining the combustion bomb burning rate of a fuel-rich gas generator propellant sample using the ultrasonic pulse-echo technique. The advanced digital method, which places user defined limits on the search for the ultrasonic echo from the burning surface, is computationally faster than the previous cross correlation method, and is able to analyze data for this class of propellant that the previous cross correlation data reduction method could not. For the conditions investigated, the best-fit burning rate law at 800 psi from the ultrasonic technique and advanced cross correlation method is within 3 percent of an independent analysis of the same data, and is within 5 percent of the best-fit burning rate law found from parallel research of the same propellant in a motor configuration.

In response to recently renewed interest in thermoelectrics, this paper reports a novel compact, multifunctional test structure to measure the in-plane thermoelectric figure of merit ZT of thin films. All material parameters contributing to ZT = S2Tκ−1ρ−1 are determined on a single sample with dimensions of about 500×500 µm2. These are the Seebeck coefficient S, the thermal conductivity κ, and the electrical resistivity ρ. The method can be applied to thin films deposited at high temperature (T), such as poly-Si, and at low T, such as metal layers. We report the temperature-dependent ZT of n-doped poly-Si from 300 to 380 K, as well as the application of the device to Al thin films.

In-plane thermal conduction and phonon transport in both single-crystalline and polycrystalline Si two-dimensional phononic crystal (PnC) nanostructures were investigated at room temperature. The impact of phononic patterning on thermal conductivity was larger in polycrystalline Si PnCs than in single-crystalline Si PnCs. The difference in the impact is attributed to the difference in the thermal phonon mean free path (MFP) distribution induced by grain boundary scattering in the two materials. Grain size analysis and numerical simulation using the Monte Carlo technique indicate that grain boundaries and phononic patterning are efficient phonon scattering mechanisms for different MFP length scales. This multiscale phonon scattering structure covers a large part of the broad distribution of thermal phonon MFPs and thus efficiently reduces thermal conduction.

Metallic tungsten (W) was initially assumed to be environmentally benign and a green alternative to lead. However, subsequent investigations showed that fishing weights and munitions containing elemental W can fragment and oxidize into complex monomeric and polymeric tungstate (WO4) species in the environment; this led to increased solubility and mobility in soils and increased bioaccumulation potential in plant and animal tissues. Here we expand on the results of our previous research, which examined tungsten toxicity, bioaccumulation, and compartmentalization into organisms, and present in this research that the bioaccumulation of W was related to greater than 50% reduction in the mechanical properties of the snail (Otala lactea), based on depth-sensing nanoindentation. Synchrotron-based X-ray fluorescence maps and X-ray diffraction measurements confirm the integration of W in newly formed layers of the shell matrix with the observed changes in shell biomechanical properties, mineralogical composition, and crystal orientation. With further development, this technology could be employed as a biomonitoring tool for historic metals contamination since unlike the more heavily studied bioaccumulation into soft tissue, shell tissue does not actively eliminate contaminants.

Nanoscale ingredients in commercial products represent a point of emerging environmental concern due to recent findings that correlate toxicity with small particle size. A weight-of-evidence (WOE) approach based upon multiple lines of evidence (LOE) is developed here to assess nanomaterials as they exist in consumer product formulations, providing a qualitative assessment regarding the presence of nanomaterials, along with a baseline estimate of nanoparticle concentration if nanomaterials do exist. Electron microscopy, analytical separations, and X-ray detection methods were used to identify and characterize nanomaterials in sunscreen formulations. The WOE/LOE approach as applied to four commercial sunscreen products indicated that all four contained at least 10% dispersed primary particles having at least one dimension

Provided the rapid emergence of novel technologies containing engineered nanomaterials, there is a need to better understand the potential environmental, health, and safety effects of nanotechnologies before wide-scale deployment. However, the unique properties of nanomaterials and uncertainty regarding applicable test methods have led to a lack of consensus regarding the collection and evaluation of data related to hazard and exposure potentials. Often, overly conservative approaches to characterization and data collection result in prolonged, unfocused, or irrelevant testing, which increases costs and delays deployment. In this paper, we provide a novel testing guidance framework for determining whether a nanotechnology has the potential to release material with nano-specific parameters that pose a risk to humans or the environment. The framework considers methods to categorize nanotechnologies by their structure and within their relevant-use scenarios to inform testing in a time- and resource-limited reality. Based on the precedent of dredged sediment testing, a five-tiered approach is proposed in which opportunities are presented to conclude testing once sufficient risk-related information has been collected, or that the technology in question does not require nano-specific scrutiny. A series of screening stages are suggested, covering relevant aspects including size, surface area, distribution, unique behaviors, and release potential. The tiered, adaptive guidance approach allows users to concentrate on collecting the most relevant data, thus accelerating technology deployment while minimizing risk.

A Disaster Management System (DMS) is very important for countries with multiple disasters, such as Chile. In the world (also in Chile)different disasters (earthquakes, tsunamis, volcanic eruption, fire or other natural or man-made disasters) happen and have an effect on the population. It is also possible that two or more disasters occur at the same time. This meansthata multi-risk situation must be mastered. To handle such a situation a Decision Support System (DSS) based on multiagents is a suitable architecture. The most known DMSs are concernedwith only a singledisaster (sometimes thecombination of earthquake and tsunami) and often with a particular disaster. Nevertheless, a DSS helps for a better real-time response. Analyze the existing systems in the literature and expand them for multi-risk disasters to construct a well-organized system is the proposal of our work. The here shown work is an approach of a multi-risk system, which needs an architecture and well defined aims. 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Structural biomaterials such as nacre, bone, and fish scales possess unique structures that have hierarchical spatial configurations, which provide excellent mechanical properties when compared to their individual constituents. These observations have been the motivation for designing and characterizing bioinspired materials with high strength, high stiffness, and corrosion-resistant properties while at the same time being environmentally friendly. It has been demonstrated that polymer-clay nanocomposites can simulate the behavior of nacreous biomaterials such as abalone shell. Mechanical, thermal, and microstructural analyses characterized solution-cast polyvinyl alcohol (PVA)/montmorillonite (MMT) nanocomposite properties over compositions ranging from the neat polymer to 25% volume fraction of MMT nanoclay. Uniaxial tensile experiments were performed at displacement rates of 1 mm/min and 50 mm/min. Strength values are similar to those shown by nacre and represent a homogeneous dispersion of the MMT in the polymer matrix. Strength-to-weight ratios are similar to many structural metals.

The changes in hydrated cement composition were measured as a means of quantifying the impact of nano silica size and surface area on cementitious properties. Nano silica dispersions were dosed to have an equal amount of exposed and reactive silica surface area, which contribute to pozzolanic reaction. The amount of calcium hydroxide was measured through thermogravimetric analysis to identify hydrate growth. The chemical shrinkage and compressive strength were also evaluated as a means to understand the impact that nano silica had on the early stages of hydration. Cement composites receiving the higher dosages of the larger nano silica particles exhibited higher levels of enhancement, showing decreased calcium hydroxide, decreased chemical shrinkage and increased compressive strength. The smaller nano silica particles exhibited enhancements at lower dosages, but at higher dosages an increase in calcium hydroxide, an increase in chemical shrinkage, and a decrease in compressive strength was recognized.

Background & Aims: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Improved treatments for advanced HCC are urgently needed. The recently identified human sulfatase 1 enzyme (SULF1) desulfates cell surface heparan sulfate glycosaminoglycans and down-regulates cell growth signaling in HCC cells in vitro. While investigating the epigenetic regulation of SULF1, we discovered that histone H4 acetylation is up-regulated by SULF1 in HCC cells. Histone deacetylase (HDAC) inhibitors reprogram cellular gene expression through the acetylation of nucleosomal histones and promote cell growth arrest and apoptosis. Hence, they are a promising modality for cancer treatment. Methods: To explore the interaction between SULF1 expression and HDAC inhibitor action, we examined the effects of SULF1 expression on HCC cells and xenografts treated with HDAC inhibitors. Results: (1) Forced expression of SULF1 significantly delayed the growth of Huh7 and Hep3B xenografts in nude mice in vivo. (2) SULF1 increased histone H4 acetylation by modulation of cellular HDAC and histone acetyltransferase activities. (3) SULF1 enhanced the induction of apoptosis by the HDAC inhibitors apicidin and scriptaid. (4) SULF1 enhanced the inhibition of tumor growth, migration, and angiogenesis by HDAC inhibitors. We also demonstrate that knockdown of SULF1 with shRNA constructs up-regulates phosphorylation of AKT and Erk and attenuates apicidin-induced apoptosis. The interaction between SULF1 and apicidin was confirmed in vivo in Huh7 and Hep3B xenografts. Conclusions: These results show that SULF1 promotes histone H4 acetylation, potentiates the effects of HDAC inhibitors, and inhibits HCC tumorigenesis.

Background: Limitations in antiemetic options have resulted in increased use of intravenous promethazine. However, this drug has significant sedative effects with its standard dosage of 25 mg, especially when used in conjunction with narcotic analgesics. While studies have revealed the bioavailability of enteric promethazine to be 25%, current dosing references suggest identical dosing regardless of the route of administration. Objective: To compare the antiemetic efficacy and sedative effects of low-dose intravenous promethazine (6.25 or 12.5 mg) with intravenous ondansetron 4 mg. Methods: We assessed inpatients with noncritical conditions at Anne Arundel Medical Center who were treated for nausea or vomiting from any cause except chemotherapy or pregnancy. Forty-six patients received low-dose promethazine and 41 received ondansetron. Statistical analysis was carried out for significant differences in efficacy and sedation. Results: For patients who received intravenous promethazine 6.25 or 12.5 mg, nausea and vomiting were relieved at one hour in 74% and 68%, respectively, compared with 59% for intravenous ondansetron 4 mg. Results at 3 hours were 67% and 80% for promethazine and 71% for ondansetron. Median sedation scores at one hour were equal at 3 for promethazine and ondansetron (4 = fully awake); at 3 hours, the median scores were 4 and 3.5, respectively. There were no statistically significant differences among any of these results. Conclusions: Low-dose (6.25 mg) intravenous promethazine relieves nausea and vomiting as effectively as intravenous ondansetron 4 mg.