A modification of the convective constraint release mechanism in the molecular stress function model giving enhanced vortex growth

The molecular stress function model with convective constraint release (MSF with CCR) constitutive model [J. Rheol. 45 (2001), 1387] is capable of fitting all viscometric data for IUPAC LDPE, with only two adjustable parameters (with difference found only on reported ¿steady-state¿ elongational viscosities). The full MSF with CCR model is implemented in a backwards particle-tracking implementation, using an adaptive method for the computation of relative stretch that reduces simulation time many-fold, with insignificant loss of accuracy. The model is shown to give improved results over earlier versions of the MSF (without CCR) when compared to well-known experimental data from White and Kondo [J. non-Newt. Fluid Mech., 3 (1977), 41]; but still to under-predict contraction flow opening angles. The discrepancy is traced to the interaction between the rotational dissipative function and the large stretch levels caused by the contraction flow. A modified combination of dissipative functions in the constraint release mechanism is proposed, which aims to reduce this interaction to allow greater strain hardening in a mixed flow. The modified constraint release mechanism is shown to fit viscometric rheological data equally well, but to give opening angles in the complex contraction flow that are much closer to the experimental data from White and Kondo. It is shown (we believe for the first time) that a constitutive model demonstrates an accurate fit to all planar elongational, uniaxial elongational and shear viscometric data, with a simultaneous agreement with this well-known experimental opening angle data. The sensitivity of results to inaccuracies caused by representing the components of the deformation gradient tensor to finite precision is examined; results are found to be insensitive to even large reductions in the precision used for the representation of components. It is shown that two models that give identical response in elongational flow, and a very similar fit to available shear data, give significantly different results in flows containing a mix of deformation modes. The implication for constitutive models is that evaluation against mixed deformation mode flow data is desirable in addition to evaluation against viscometric measurements

Determination of the Defining Boundary in Nuclear Magnetic Resonance Diffusion Experiments

While nuclear magnetic resonance diffusion experiments are widely used to resolve structures confining the diffusion process, it has been elusive whether they can exactly reveal these structures. This question is closely related to X-ray scattering and to Kac's "hear the drum" problem. Although the shape of the drum is not "hearable", we show that the confining boundary of closed pores can indeed be detected using modified Stejskal-Tanner magnetic field gradients that preserve the phase information and enable imaging of the average pore in a porous medium with a largely increased signal-to-noise ratio.Comment: 13 pages, 2 figure

Lysosomotropic Properties of Weakly Basic Anticancer Agents Promote Cancer Cell Selectivity In Vitro

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Drug distribution in cells is a fundamentally important, yet often overlooked, variable in drug efficacy. Many weakly basic anticancer agents accumulate extensively in the acidic lysosomes of normal cells through ion trapping. Lysosomal trapping reduces the activity of anticancer drugs, since anticancer drug targets are often localized in the cell cytosol or nucleus. Some cancer cells have defective acidification of lysosomes, which causes a redistribution of trapped drugs from the lysosomes to the cytosol. We have previously established that such differences in drug localization between normal and cancer cells can contribute to the apparent selectivity of weakly basic drugs to cancer cells in vitro. In this work, we tested whether this intracellular distribution-based drug selectivity could be optimized based on the acid dissociation constant (pKa) of the drug, which is one of the determinants of lysosomal sequestration capacity. We synthesized seven weakly basic structural analogs of the Hsp90 inhibitor geldanamycin (GDA) with pKa values ranging from 5 to 12. The selectivity of each analog was expressed by taking ratios of anti-proliferative IC50 values of the inhibitors in normal fibroblasts to the IC50 values in human leukemic HL-60 cells. Similar selectivity assessments were performed in a pair of cancer cell lines that differed in lysosomal pH as a result of siRNA-mediated alteration of vacuolar proton ATPase subunit expression. Optimal selectivity was observed for analogs with pKa values near 8. Similar trends were observed with commercial anticancer agents with varying weakly basic pKa values. These evaluations advance our understanding of how weakly basic properties can be optimized to achieve maximum anticancer drug selectivity towards cancer cells with defective lysosomal acidification in vitro. Additional in vivo studies are needed to examine the utility of this approach for enhancing selectivity

Jamming and Stress Propagation in Particulate Matter

We present simple models of particulate materials whose mechanical integrity arises from a jamming process. We argue that such media are generically "fragile", that is, they are unable to support certain types of incremental loading without plastic rearrangement. In such models, fragility is naturally linked to the marginal stability of force chain networks (granular skeletons) within the material. Fragile matter exhibits novel mechanical responses that may be relevant to both jammed colloids and cohesionless assemblies of poured, rigid grains.Comment: LATEX, 3 Figures, elsart.cls style file, 11 page

A study of the quadratic molecular stress function constitutive model in simulation

Constitutive models that conform to separable KBKZ specification have been shown to fit steady-state strain hardening rheological data in planar and uniaxial elongational flows, but with inaccuracy in the rate of strain hardening. The single parameter Molecular Stress Function model of Wagner [Rheol. Acta, 39 (2000), 97-109] has been shown to accurately fit the rise-rate in experimental data for a number of strain hardening and strain softening materials. We study this models accuracy against the well characterised IUPAC LDPE data, and present a method for full implementation of this model for flow solution which is suitable for incorporating into existing separable KBKZ software. A new method for particle tracking in arbitrarily aligned meshes, which is efficient and robust, is given. The Quadratic Molecular Stress Function (QMSF) model is compared to existing separable KBKZ based models, including one which is capable of giving planar strain hardening; the QMSF is shown to fit experimental rheological and contraction flow data more convincingly. The issue of `negative correction pressures¿ notable in some Doi-Edwards based models is addressed. The cause is identified, and leads to a logical method of calculation which does not give these anomalous results

Aging (Albany NY)

The combination of functional genomics with next generation sequencing facilitates new experimental strategies for addressing complex biological phenomena. Here, we report the identification of a gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1p) via whole-genome re-sequencing of a dominantSaccharomyces cerevisiae mutant obtained by chemical mutagenesis. Yeast strain K6001, a screening system for lifespan phenotypes, was treated with ethyl methanesulfonate (EMS). We isolated an oxidative stress-resistant mutant (B7) which transmitted this phenotype in a background-independent, monogenic and dominant way. By massive parallel pyrosequencing, we generated an 38.8 fold whole-genome coverage of the strains, which differed in 12,482 positions from the reference (S288c) genome. Via a subtraction strategy, we could narrow this number to 13 total and 4 missense nucleotide variations that were specific for the mutant. Via expression in wild type backgrounds, we show that one of these mutations, exchanging a residue in the peroxiredoxin Tsa1p, was responsible for the mutant phenotype causing background-independent dominant oxidative stress-resistance. These effects were not provoked by altered Tsa1p levels, nor could they be simulated by deletion, haploinsufficiency or over-expression of the wild-type allele. Furthermore, via both a mother-enrichment technique and a micromanipulation assay, we found a robust premature aging phenotype of this oxidant-resistant strain. Thus, TSA1-B7 encodes for a novel dominant form of peroxiredoxin, and establishes a new connection between oxidative stress and aging. In addition, this study shows that the re-sequencing of entire genomes is becoming a promising alternative for the identification of functional alleles in approaches of classic molecular genetics

Efeitos da aplicação do boro em solos sob vegetação de cerrado

The present was carried out with the objective of studying the effects of boron applications on Red Yellow Latosol - sandy phase and on Regossol (Quartzosas Sand) under "Cerrado" vegetation of São Simão, São Paulo, State. Chemical determinations of soluble boron were made on soil samples of the experimental area collected before and after dolomitic line applications. Complementary biological tests of boron were also made, employing sunflower (Helianthus annus L.). Simultaneously, fold experiment was carried and with dry (Phaseolus vulgaris L.) to study boron applications. The main conclusions were the followings: 1 - Biologycal tests with sumflower were correlated with chemical analysis indicating that both soil units were slightly or no boron deficient. 2 - The soil classified how Regosol (Quartzous Sand) showed a larger Boron content than the Red Yellow Latosol-sandy phase. 3 - There has been no response of dry beans to boron on both soils.O presente trabalho teve como objetivo estudar os efeitos da aplicação de boro em duas unidades de solo cobertas com vegetação de cerrado, classificadas co-como, Latossolo Vermelho Amarelo-fase arenosa e Regossolo (Areas Quartzosas), que ocorrem no município de São Simão, no Estado de São Paulo. Foram feitas determinações químicas de boro solúvel em amostras colhidas nas áreas experimentais antes e depois do tratamento dos solos com calagem. As determinações do boro foram complementados com testes biológicos do girassol (Helianthus annuus L.). Simultaneamente foram conduzidos ensaios de campo para estudos sobre a aplicação de doses crescentes de boro no feijoeiro (Phaseolus vulgaris L.). As conclusões do trabalho foram as seguintes: 1 - O teste do girassol apresentou boa concordância com os testes químicos, indicando que as duas unidades de solo são ligeiramente deficientes ou não deficientes em boro. 2 - O solo classificado como Regossolo (Areias Quartzosas) mostrou-se mais elevado em boro do que o Latossol Vermelho Amarelo - fase arenosa. 3 - Não houve efeito da aplicação de boro na produção do feijoeiro

Efeitos da aplicação de zinco em solos sob vegetação de cerrado

The present work was carried out with the objetive of sudying the effects of zinc applications on Red Yellow Latosol-sandy phase on Quartzous Sand under "cerrado" vegetation of São Simão, São Paulo State. Chemical determinations of soluble zinc were made on soil samples of the experimental area collected before and after dolomitic lime applications. Complementary microbiological tests of zinc were also made, employing the test of Aspergillus niger for zinc. Simultaneously, field experiments were carried out with con (Zea mays L.) apd dry beans (Phaseolus vulgaris L.) to study zinc applications. A greenhouse experiment was also carried out corn seeded in pots to study zinc applications. The main conlusions were the followings: 1. Microbiological tests were correlated with chemical analysis and with responses of corn an field conditions. 2. Corn response to zinc was observed on Quartzous Sand up to on economical dosis of 2,4 kg zinc/ha. 3. There wasn't responses from corn to zinc applications on the Red Yellow Latosol-Sandy phase. 4. There has been no response of dry beans to zinc on both soils. 5. The experiment on pots with corn was not eficient to show response to applications of zinc.O presente trabalho teve como objetivo estudar os efeitos da aplicação de zinco em duas unidades de solos originalmente cobertas com vegetação de cerrado, classificadas como Latossolo Vermelho Amarelo-fase arenosa e Areias Quartzosas, que ocorrem no Município de São Simão no Estado de São Paulo Foram feitas determinações químicas do zinco solúvel em HCl 0,1 N, em amostras de solos antes e depois de terem recebido a calagem. As determinações de zinco foram complementadas com o teste microbiológico do Aspergilus niger Simultaneamente, foram conduzidos ensaios de campo com milho (Zea mays L.) e feijão Phaseolus vulgaris L.) para estudar os efeitos da aplicação de zinco nas duas unidades de solo. Outros experimentos com milho foram desenvolvidos sob condições controladas, em casa de vegetação, para estudos de aplicação de zinco. As conclusões do trabalho foram as seguintes: 1. Os resultados dos ensaios microbiológicos mostraram boa concordância com os testes químicos e com a resposta do milho a aplicação de zinco em condições de campo. 2. A cultura do milho deu boas respostas a aplicação de zinco quando cultido nos solos Areias Quartzosas, correspondendo a uma dose econômica de 2,4 kg/ha de zinco. 3. Não houve efeito do zinco para o milho quando este foi cultivado no Latossolo Vermelho Amarelo-fase arenosa. 4. Não houve efeitos do zinco na produção do feijoeiro nas duas unidades de solos. 5. O ensaio de vasos usando o milho como planta teste não foi eficiente na resposta dos solos as aplicações de zinco

GRAVITY: getting to the event horizon of Sgr A*

We present the second-generation VLTI instrument GRAVITY, which currently is in the preliminary design phase. GRAVITY is specifically designed to observe highly relativistic motions of matter close to the event horizon of Sgr A*, the massive black hole at center of the Milky Way. We have identified the key design features needed to achieve this goal and present the resulting instrument concept. It includes an integrated optics, 4-telescope, dual feed beam combiner operated in a cryogenic vessel; near infrared wavefront sensing adaptive optics; fringe tracking on secondary sources within the field of view of the VLTI and a novel metrology concept. Simulations show that the planned design matches the scientific needs; in particular that 10 microarcsecond astrometry is feasible for a source with a magnitude of K=15 like Sgr A*, given the availability of suitable phase reference sources.Comment: 13 pages, 11 figures, to appear in the conference proceedings of SPIE Astronomical Instrumentation, 23-28 June 2008, Marseille, Franc

The Turkey Ig-like receptor family: identification, expression and function.

The chicken leukocyte receptor complex located on microchromosome 31 encodes the chicken Ig-like receptors (CHIR), a vastly expanded gene family which can be further divided into three subgroups: activating CHIR-A, bifunctional CHIR-AB and inhibitory CHIR-B. Here, we investigated the presence of CHIR homologues in other bird species. The available genome databases of turkey, duck and zebra finch were screened with different strategies including BLAST searches employing various CHIR sequences, and keyword searches. We could not identify CHIR homologues in the distantly related zebra finch and duck, however, several partial and complete sequences of CHIR homologues were identified on chromosome 3 of the turkey genome. They were designated as turkey Ig-like receptors (TILR). Using cDNA derived from turkey blood and spleen RNA, six full length TILR could be amplified and further divided according to the typical sequence features into one activating TILR-A, one inhibitory TILR-B and four bifunctional TILR-AB. Since the TILR-AB sequences all displayed the critical residues shown to be involved in binding to IgY, we next confirmed the IgY binding using a soluble TILR-AB1-huIg fusion protein. This fusion protein reacted with IgY derived from various gallinaceous birds, but not with IgY from other bird species. Finally, we tested various mab directed against CHIR for their crossreactivity with either turkey or duck leukocytes. Whereas no staining was detectable with duck cells, the CHIR-AB1 specific mab 8D12 and the CHIR-A2 specific mab 13E2 both reacted with a leukocyte subpopulation that was further identified as thrombocytes by double immunofluorescence employing B-cell, T-cell and thrombocyte specific reagents. In summary, although the turkey harbors similar LRC genes as the chicken, their distribution seems to be distinct with predominance on thrombocytes rather than lymphocytes