Modeling Micro-Porous Surfaces for Secondary Electron Emission Control to Suppress Multipactor

This work seeks to understand how the topography of a surface can be engineered to control secondary electron emission (SEE) for multipactor suppression. Two unique, semi-empirical models for the secondary electron yield (SEY) of a micro-porous surface are derived and compared. The first model is based on a two-dimensional (2D) pore geometry. The second model is based on a three-dimensional (3D) pore geometry. The SEY of both models is shown to depend on two categories of surface parameters: chemistry and topography. An important parameter in these models is the probability of electron emissions to escape the surface pores. This probability is shown by both models to depend exclusively on the aspect ratio of the pore (the ratio of the pore height to the pore diameter). The increased accuracy of the 3D model (compared to the 2D model) results in lower electron escape probabilities with the greatest reductions occurring for aspect ratios less than two. In order to validate these models, a variety of micro-porous gold surfaces were designed and fabricated using photolithography and electroplating processes. The use of an additive metal-deposition process (instead of the more commonly used subtractive metal-etch process) provided geometrically ideal pores which were necessary to accurately assess the 2D and 3D models. Comparison of the experimentally measured SEY data with model predictions from both the 2D and 3D models illustrates the improved accuracy of the 3D model. For a micro-porous gold surface consisting of pores with aspect ratios of two and a 50% pore density, the 3D model predicts that the maximum total SEY will be one. This provides optimal engineered surface design objectives to pursue for multipactor suppression using gold surfaces

Salsalate treatment improves glycemia without altering adipose tissue in nondiabetic obese hispanics.

ObjectiveSalsalate treatment has well-known effects on improving glycemia, and the objective of this study was to examine whether the mechanism of this effect was related to changes in adipose tissue.MethodsA randomized double-blind and placebo-controlled trial in obese Hispanics (18-35 years) was conducted. The intervention consisted of 4 g day(-1) of salsalate (n = 11) versus placebo (n = 13) for 4 weeks. Outcome measures included glycemia, adiposity, ectopic fat, and adipose tissue gene expression and inflammation.ResultsIn those receiving salsalate, plasma fasting glucose decreased by 3.4% (P < 0.01), free fatty acids decreased by 42.5% (P = 0.06), and adiponectin increased by 27.7% (P < 0.01). Salsalate increased insulin AUC by 38% (P = 0.01) and HOMA-B by 47.2% (P < 0.01) while estimates of insulin sensitivity/resistance were unaffected. These metabolic improvements occurred without changes in total, abdominal, visceral, or liver fat. Plasma markers of inflammation/immune activation were unchanged following salsalate. Salsalate had no effects on adipose tissue including adipocyte size, presence of crown-like structures, or gene expression of adipokines, immune cell markers, or cytokines downstream of NF-κB with the exception of downregulation of IL-1β (P < 0.01).ConclusionsFindings suggest that metabolic improvements in response to salsalate occurred without alterations in adiposity, ectopic fat, or adipose tissue gene expression and inflammation

Automated Synthesis of Tableau Calculi

This paper presents a method for synthesising sound and complete tableau calculi. Given a specification of the formal semantics of a logic, the method generates a set of tableau inference rules that can then be used to reason within the logic. The method guarantees that the generated rules form a calculus which is sound and constructively complete. If the logic can be shown to admit finite filtration with respect to a well-defined first-order semantics then adding a general blocking mechanism provides a terminating tableau calculus. The process of generating tableau rules can be completely automated and produces, together with the blocking mechanism, an automated procedure for generating tableau decision procedures. For illustration we show the workability of the approach for a description logic with transitive roles and propositional intuitionistic logic.Comment: 32 page

Small-molecule lysophosphatidic acid receptor 5 (LPAR5) antagonists: versatile pharmacological tools to regulate inflammatory signaling in BV-2 microglia cells

Lysophosphatidic acid (LPA) species in the extracellular environment induce downstream signaling via six different G protein-coupled receptors (LPAR1-6). These signaling cascades are essential for normal brain development and function of the nervous system. However, in response to acute or chronic central nervous system (CNS) damage, LPA levels increase and aberrant signaling events can counteract brain function. Under neuro-inflammatory conditions signaling along the LPA/LPAR5 axis induces a potentially neurotoxic microglia phenotype indicating the need for new pharmacological intervention strategies. Therefore, we compared the effects of two novel small-molecule LPAR5 antagonists on LPA-induced polarization parameters of the BV-2 microglia cell line. AS2717638 is a selective piperidine-based LPAR5 antagonist (IC(50) 0.038 μM) while compound 3 is a diphenylpyrazole derivative with an IC(50) concentration of 0.7 μM in BV-2 cells. Both antagonists compromised cell viability, however, at concentrations above their IC(50) concentrations. Both inhibitors blunted LPA-induced phosphorylation of STAT1 and STAT3, p65, and c-Jun and consequently reduced the secretion of pro-inflammatory cyto-/chemokines (IL-6, TNFα, IL-1β, CXCL10, CXCL2, and CCL5) at non-toxic concentrations. Both compounds modulated the expression of intracellular (COX-2 and Arg1) and plasma membrane-located (CD40, CD86, and CD206) polarization markers yet only AS2717638 attenuated the neurotoxic potential of LPA-activated BV-2 cell-conditioned medium towards CATH.a neurons. Our findings from the present in vitro study suggest that the two LPAR5 antagonists represent valuable pharmacological tools to interfere with LPA-induced pro-inflammatory signaling cascades in microglia

NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases

Transformation by tyrosine kinase oncogenes in myeloid malignancies, including BCR-ABL in chronic myeloid leukemia, FLT3ITD in acute myeloid leukemia (AML) or JAK2V617F in myeloproliferative neoplasms (MPN), is associated with increased growth and cytoskeletal abnormalities. Using targeted approaches against components of the superoxide-producing NADPH-oxidases, including NOX2, NOX4 and the common p22phox subunit of NOX1-4, myeloid cells were found to display reduced cell growth and spontaneous migration. Consistent with a role of NOX as regulators of membrane proximal signaling events in non-phagocytic cells, NOX2 and NOX4 were not involved in the excess production of intracellular reactive oxygen species and did not significantly increase oxygen consumption. All NOX family members are controlled in part through levels of the rate-limiting substrate NADPH, which was found to be significantly elevated in tyrosine kinase oncogene transformed cells. Also, reduced phosphorylation of the actin filament crosslinking protein MARCKS in response to suppression of p22phox hints at a novel effector of NOX signaling. MARCKS was also found to be required for increased migration. Overall, these data suggest a model whereby NOX links metabolic NADPH production to cellular events that directly contribute to transformation

Registration of N619 to N640 Grain Sorghum Lines with Waxy or Wild-Type Endosperm

Sorghum [Sorghum bicolor (L.) Moench] lines N619 to N636 (A lines; Reg. No. GS-699 to GS-716, PI 670134 to PI 670151); N619 to N636 (B lines; Reg. No. GS-721 to GS-738, PI 671777 to PI 671794); and N637 to N640 (R lines; Reg. No. GS-717 to GS-720, PI 670152 to PI 670155) comprise nine pairs of seed parent (A/B) lines, and two pairs of pollinator (R) lines (11 pairs total) that are near-isogenic for waxy (low-amylose) or wildtype endosperm. Breeding work was conducted jointly by the USDA–ARS and the Agricultural Research Division, Institute of Agriculture and Natural Resources, University of Nebraska, and the lines were released in May 2014. Release of these lines makes available two different waxy (wx) alleles (wxa and wxb) for development of grain sorghum as a source of lowamylose starch, whose end use is targeted to the ethanol and food industries. In particular, the release of wx and wild-type near-isogenic pairs facilitates the evaluation of agronomic performance of wx genotypes, and the release of both A/B and R lines facilitates the production of waxy grain hybrids

On the Hybrid Extension of CTL and CTL+

The paper studies the expressivity, relative succinctness and complexity of satisfiability for hybrid extensions of the branching-time logics CTL and CTL+ by variables. Previous complexity results show that only fragments with one variable do have elementary complexity. It is shown that H1CTL+ and H1CTL, the hybrid extensions with one variable of CTL+ and CTL, respectively, are expressively equivalent but H1CTL+ is exponentially more succinct than H1CTL. On the other hand, HCTL+, the hybrid extension of CTL with arbitrarily many variables does not capture CTL*, as it even cannot express the simple CTL* property EGFp. The satisfiability problem for H1CTL+ is complete for triply exponential time, this remains true for quite weak fragments and quite strong extensions of the logic

Evaluation of Interallelic \u3ci\u3ewaxy\u3c/i\u3e, Hetero\u3ci\u3ewaxy\u3c/i\u3e, and Wild-Type Grain Sorghum Hybrids

Four near-isogenic Wheatland x Tx430 grain sorghum [Sorghum bicolor (L.) Moench] hybrids differing in allelic status at the Waxy locus were grown in yield trials to determine their potential to expand existing sources of low-amylose starch. The hypothesis tested was that agronomic performance and grain yield do not differ among hybrid genotypes. Hybrids were generated in a two-by-two factorial design using wxb and wild-type (WT) Wheatland as female parents with wxa and WT Tx430 as male parents. Yield trials were conducted at two Nebraska locations in 2009 and 2010. No differences were observed for field emergence, but grain yield of the interallelic waxy (wxb x wxa) hybrid was 330 kg ha−1 greater than the WT x WT hybrid (P = 0.0482). The wxb x Wx hybrid had the highest grain yield, 633 kg ha−1 greater than the WT (P = 0.0003). Amylose starch content was lowest for wxb x wxa (7.66 g kg−1), intermediate for wxb x Wx and Wx x wxa (25.06 and 27.20 g kg−1, respectively); and highest for WT x WT (34.80 g kg−1) (n = 4, P \u3c 0.0001). The waxy and heterowaxy hybrids evaluated in this study are promising options for commercial production of starches with reduced amylose contents in a drought-tolerant crop

EPHA2 mutations with oncogenic characteristics in squamous cell lung cancer and malignant pleural mesothelioma.

Squamous cell carcinoma (SCC) and malignant pleural mesothelioma (MPM) are thoracic malignancies with very poor prognosis and limited treatment options. It is an established fact that most of the solid tumors have overexpression of EPHA2 receptor tyrosine kinase. EPHA2 is known to exhibit opposing roles towards cancer progression. It functions in inhibiting cancer survival and migration via a ligand and tyrosine kinase dependent signaling (Y772). Whereas it is known to promote tumor progression and cell migration through a ligand-independent signaling (S897). We analyzed the expression profile and mutational status of the ephrin receptor A2 (EPHA2) in SCC and MPM cell lines and primary patient specimens. The EPHA2 receptor was found to be either overexpressed, mutated or amplified in SCC and MPM. In particular, the EPHA2 mutants A859D and T647M were interesting to explore, A859D Y772 dead mutant exhibited lower levels of phosphorylation at Y772 compared to T647M mutant. Molecular Dynamics simulations studies suggested that differential changes in conformation might form the structural basis for differences in the level of EPHA2 activation. Consequently, A859D mutant cells exhibited increased proliferation as well as cell migration compared to controls and T647M mutant. Kinomics analysis demonstrated that the STAT3 and PDGF pathways were upregulated whereas signaling through CBL was suppressed. Considered together, the present work has uncovered the oncogenic characteristics of EPHA2 mutations in SSC and MPM reinstating the dynamics of different roles of EPHA2 in cancer. This study also suggests that a combination of doxazosin and other EPHA2 inhibitors directed to inhibit the pertinent signaling components may be a novel therapeutic strategy for MPM and Non-small cell lung cancer patients who have either EPHA2 or CBL alterations