Perturbative growth of cosmological clustering .2. The two-point correlation

We use the BBGKY hierarchy equations to calculate, perturbatively, the lowest order nonlinear correction to the two-point correlation and the pair velocity for Gaussian initial conditions in a critical density matter-dominated cosmological model. We compare our results with the results obtained using the hydrodynamic equations that neglect pressure and find that the two match, indicating that there are no effects of multistreaming at this order of perturbation. We analytically study the effect of small scales on the large scales by calculating the nonlinear correction for a Dirac delta function initial two-point correlation. We find that the induced two-point correlation has a x(-6) behavior at large separations. We have considered a class of initial conditions where the initial power spectrum at small k has the form k(n) with 0 < n less than or equal to 3 and have numerically calculated the nonlinear correction to the two-point correlation, its average over a sphere and the pair velocity over a large dynamical range. We find that at small separations the effect of the nonlinear term is to enhance the clustering, whereas at intermediate scales it can act to either increase or decrease the clustering. At large scales we find a simple formula that gives a very good fit for the nonlinear correction in terms of the initial function. This formula explicitly exhibits the influence of small scales on large scales and because of this coupling the perturbative treatment breaks down at large scales much before one would expect it to if the nonlinearity were local in real space. We physically interpret this formula in terms of a simple diffusion process. We have also investigated the case n = 0, and we find that it differs from the other cases in certain respects. We investigate a recently proposed scaling property of gravitational clustering, and we find that the lowest order nonlinear terms cause deviations from the scaling relations that are strictly valid in the linear regime. The approximate validity of these relations in the nonlinear regime in l(T)-body simulations cannot be understood at this order of evolution.

Nucleation and growth characteristics of cavities during the early stages of tensile creep deformation in a superplastic zirconia-20 wt% alumina composite

Constant-stress tensile creep experiments on a superplastic 3-mol%-yttria-stabilized tetragonal zirconia composite with 20 wt% alumina revealed that cavities nucleate relatively early during tensile deformation. The number of cavities nucleated increases with increasing imposed stress. The cavities nucleate at triple points associated largely with an alumina grain, and then grow rapidly in a cracklike manner to attain dimensions on the order of the grain facet size. It is suggested that coarser-grained superplastic ceramics exhibit lower ductility due to the ease in formation of such grain boundary facet-cracks and their interlinkage to form a macroscopic crack of critical dimensions.

Insulin Growth Factor-2 Binding Protein 3 (IGF2BP3) Is a Glioblastoma-specific Marker That Activates Phosphatidylinositol 3-Kinase/Mitogen-activated Protein Kinase (PI3K/MAPK) Pathways by Modulating IGF-2

Glioblastoma is the most common and malignant form of primary astrocytoma. Upon investigation of the insulin-like growth factor (IGF) pathway, we found the IGF2BP3/IMP3 transcript and protein to be up-regulated in GBMs but not in lower grade astrocytomas (p<0.0001). IMP3 is an RNA binding protein known to bind to the 5'-untranslated region of IGF-2 mRNA, thereby activating its translation. Overexpression-and knockdown-based studies establish a role for IMP3 in promoting proliferation, anchorage-independent growth, invasion, and chemoresistance. IMP3 overexpressing B16F10 cells also showed increased tumor growth, angiogenesis, and metastasis, resulting in poor survival in a mouse model. Additionally, the infiltrating front, perivascular, and subpial regions in a majority of the GBMs stained positive for IMP3. Furthermore, two different murine glioma models were used to substantiate the above findings. In agreement with the translation activation functions of IMP3, we also found increased IGF-2 protein in the GBM tumor samples without a corresponding increase in its transcript levels. Also, in vitro IMP3 overexpression/knockdown modulated the IGF-2 protein levels without altering its transcript levels. Additionally, IGF-2 neutralization and supplementation studies established that the proproliferative effects of IMP3 were indeed mediated through IGF-2. Concordantly, PI3K and MAPK, the downstream effectors of IGF-2, are activated by IMP3 and are found to be essential for IMP3-induced cell proliferation. Thus, we have identified IMP3 as a GBM-specific proproliferative and proinvasive marker acting through IGF-2 resulting in the activation of oncogenic PI3K and MAPK pathways.

Fatigue crack growth due to overloads in plain concrete using scaling laws

Scaling laws are represented in power law form and can be utilized to extract the characteristic properties of a new phenomenon with the help of self-similar solutions. In this work, an attempt has been made to propose a scaling law analytically, for plain concrete when subjected to variable amplitude loading. Due to the application of overload on concrete structures, acceleration in the crack growth process takes place. A closed form expression has been developed to capture the acceleration in crack growth rate in conjunction with the principles of dimensional analysis and self-similarity. The proposed model accounts for parameters such as, the tensile strength, fracture toughness, overload effect and the structural size. Knowing the governed and the governing parameters of the physical problem and by using the concepts of self-similarity, a relationship is obtained between the different parameters involved. The predicted results are compared with experimental crack growth data for variable amplitude loading and are found to capture the overload effect with sufficient accuracy. Through a sensitivity analysis, fracture toughness is found to be the most dominant parameter in accelerating the crack length due to application of overload.

Polymorphic Anhydrous Cocrystals of Gallic Acid and Acetamide from Methanol: Pointers toward a Stable Cocrystal Form

Polymorphic anhydrous cocrystals generated from a methanolic solution of gallic acid monohydrate and acetamide are shown to convert to the stable form II on complete drying, and the pathway to the stable form is explained on the basis of the variability in the hydrogen bonding patterns followed by theoretical calculations.

Drosophila Erect wing (Ewg) controls mitochondrial fusion during muscle growth and maintenance by regulation of the Opa1-like gene

Mitochondrial biogenesis and morphological changes are associated with tissue-specific functional demand, but the factors and pathways that regulate these processes have not been completely identified. A lack of mitochondrial fusion has been implicated in various developmental and pathological defects. The spatiotemporal regulation of mitochondrial fusion in a tissue such as muscle is not well understood. Here, we show in Drosophila indirect flight muscles (IFMs) that the nuclear-encoded mitochondrial inner membrane fusion gene, Opa1-like, is regulated in a spatiotemporal fashion by the transcription factor/co-activator Erect wing (Ewg). In IFMs null for Ewg, mitochondria undergo mitophagy and/or autophagy accompanied by reduced mitochondrial functioning and muscle degeneration. By following the dynamics of mitochondrial growth and shape in IFMs, we found that mitochondria grow extensively and fuse during late pupal development to form the large tubular mitochondria. Our evidence shows that Ewg expression during early IFM development is sufficient to upregulate Opa1-like, which itself is a requisite for both late pupal mitochondrial fusion and muscle maintenance. Concomitantly, by knocking down Opa1-like during early muscle development, we show that it is important for mitochondrial fusion, muscle differentiation and muscle organization. However, knocking down Opa1-like, after the expression window of Ewg did not cause mitochondrial or muscle defects. This study identifies a mechanism by which mitochondrial fusion is regulated spatiotemporally by Ewg through Opa1-like during IFM differentiation and growth.

Tracing a Crystallization Pathway of an RT Liquid, 4-Fluorobenzoyl Chloride: Metastable Polytypic Form as an Intermediate Phase

When quenched with liquid N-2, a room temperature liquid, 4-fluorobenzoyl chloride, generates a new crystalline form that appears to be polytypic to the previously reported form. The structural and energetic correlations between these forms trace a crystallization pathway of the compound.

Hydrophobic hydration driven self-assembly of curcumin in water: Similarities to nucleation and growth under large metastability, and an analysis of water dynamics at heterogeneous surfaces

As the beneficial effects of curcumin have often been reported to be limited to its small concentrations, we have undertaken a study to find the aggregation properties of curcumin in water by varying the number of monomers. Our molecular dynamics simulation results show that the equilibrated structure is always an aggregated state with remarkable structural rearrangements as we vary the number of curcumin monomers from 4 to 16 monomers. We find that the curcumin monomers form clusters in a very definite pattern where they tend to aggregate both in parallel and anti-parallel orientation of the phenyl rings, often seen in the formation of beta-sheet in proteins. A considerable enhancement in the population of parallel alignments is observed with increasing the system size from 12 to 16 curcumin monomers. Due to the prevalence of such parallel alignment for large system size, a more closely packed cluster is formed with maximum number of hydrophobic contacts. We also follow the pathway of cluster growth, in particular the transition from the initial segregated to the final aggregated state. We find the existence of a metastable structural intermediate involving a number of intermediate-sized clusters dispersed in the solution. We have constructed a free energy landscape of aggregation where the metatsable state has been identified. The course of aggregation bears similarity to nucleation and growth in highly metastable state. The final aggregated form remains stable with the total exclusion of water from its sequestered hydrophobic core. We also investigate water structure near the cluster surface along with their orientation. We find that water molecules form a distorted tetrahedral geometry in the 1st solvation layer of the cluster, interacting rather strongly with the hydrophilic groups at the surface of the curcumin. The dynamics of such quasi-bound water molecules near the surface of curcumin cluster is considerably slower than the bulk signifying a restricted motion as often found in protein hydration layer. (C) 2014 AIP Publishing LLC.

Identification of a novel AMPK-PEA15 axis in the anoikis-resistant growth of mammary cells

Introduction: Matrix detachment triggers anoikis, a form of apoptosis, in most normal epithelial cells, while acquisition of anoikis resistance is a prime requisite for solid tumor growth. Of note, recent studies have revealed that a small population of normal human mammary epithelial cells (HMECs) survive in suspension and generate multicellular spheroids termed `mammospheres'. Therefore, understanding how normal HMECs overcome anoikis may provide insights into breast cancer initiation and progression. Methods: Primary breast tissue-derived normal HMECs were grown as adherent monolayers or mammospheres. The status of AMP-activated protein kinase (AMPK) and PEA15 signaling was investigated by immunoblotting. Pharmacological agents and an RNA interference (RNAi) approach were employed to gauge their roles in mammosphere formation. Immunoprecipitation and in vitro kinase assays were undertaken to evaluate interactions between AMPK and PEA15. In vitro sphere formation and tumor xenograft assays were performed to understand their roles in tumorigenicity. Results: In this study, we show that mammosphere formation by normal HMECs is accompanied with an increase in AMPK activity. Inhibition or knockdown of AMPK impaired mammosphere formation. Concomitant with AMPK activation, we detected increased Ser(116) phosphorylation of PEA15, which promotes its anti-apoptotic functions. Inhibition or knockdown of AMPK impaired PEA15 Ser(116) phosphorylation and increased apoptosis. Knockdown of PEA15, or overexpression of the nonphosphorylatable S116A mutant of PEA15, also abrogated mammosphere formation. We further demonstrate that AMPK directly interacts with and phosphorylates PEA15 at Ser(116) residue, thus identifying PEA15 as a novel AMPK substrate. Together, these data revealed that AMPK activation facilitates mammosphere formation by inhibition of apoptosis, at least in part, through Ser(116) phosphorylation of PEA15. Since anoikis resistance plays a critical role in solid tumor growth, we investigated the relevance of these findings in the context of breast cancer. Significantly, we show that the AMPK-PEA15 axis plays an important role in the anchorage-independent growth of breast cancer cells both in vitro and in vivo. Conclusions: Our study identifies a novel AMPK-PEA15 signaling axis in the anchorage-independent growth of both normal and cancerous mammary epithelial cells, suggesting that breast cancer cells may employ mechanisms of anoikis resistance already inherent within a subset of normal HMECs. Thus, targeting the AMPK-PEA15 axis might prevent breast cancer dissemination and metastasis.

Do carboximide-carboxylic acid combinations form co-crystals? The role of hydroxyl substitution on the formation of co-crystals and eutectics

Carboxylic acids, amides and imides are key organic systems which provide understanding of molecular recognition and binding phenomena important in biological and pharmaceutical settings. In this context, studies of their mutual interactions and compatibility through co-crystallization may pave the way for greater understanding and new applications of their combinations. Extensive co-crystallization studies are available for carboxylic acid/amide combinations, but only a few examples of carboxylic acid/imide co-crystals are currently observed in the literature. The non-formation of co-crystals for carboxylic acid/imide combinations has previously been rationalized, based on steric and computed stability factors. In the light of the growing awareness of eutectic mixtures as an alternative outcome in co-crystallization experiments, the nature of various benzoic acid/cyclic imide combinations is established in this paper. Since an additional functional group can provide sites for new intermolecular interactions and, potentially, promote supramolecular growth into a co-crystal, benzoic acids decorated with one or more hydroxyl groups have been systematically screened for co-crystallization with one unsaturated and two saturated cyclic imides. The facile formation of an abundant number of hydroxybenzoic acid/cyclic carboximide co-crystals is reported, including polymorphic and variable stoichiometry co-crystals. In the cases where co-crystals did not form, the combinations are shown invariably to result in eutectics. The presence or absence and geometric disposition of hydroxyl functionality on benzoic acid is thus found to drive the formation of co- crystals or eutectics for the studied carboxylic acid/imide combinations.

Innovation and growth of engineering SMEs in Bangalore: Why do only some innovate and only some grow faster?

This paper probes two research questions by ascertaining the factors which distinguish (i) innovative SMEs from those which are not, and (ii) SMEs which experienced a higher sales growth from those which experienced a lower sales growth, with reference to 197 engineering industry SMEs in Bangalore city. The differentiating factors between innovative and non-innovative SMEs brought out that SMEs must have ``own resources and capabilities'' in the form of internal strength and definite internal strategy if they have to innovate successfully. Younger and smaller firms which are ``entrepreneurial'' in nature and which are innovative contributed to higher sales growth of SMEs compared to older and larger firms which are ``salary-substitute firms'' in nature and which are not innovative. (C) 2015 Elsevier B.V. All rights reserved.

Ac2PIM-responsive miR-150 and miR-143 Target Receptor-interacting Protein Kinase 2 and Transforming Growth Factor Beta-activated Kinase 1 to Suppress NOD2-induced Immunomodulators

Specific and coordinated regulation of innate immune receptor-driven signaling networks often determines the net outcome of the immune responses. Here, we investigated the cross-regulation of toll-like receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)2 pathways mediated by Ac2PIM, a tetra-acylated form of mycobacterial cell wall component and muramyl dipeptide (MDP), a peptidoglycan derivative respectively. While Ac2PIM treatment of macrophages compromised their ability to induce NOD2-dependent immunomodulators like cyclooxygenase (COX)-2, suppressor of cytokine signaling (SOCS)-3, and matrix metalloproteinase (MMP)-9, no change in the NOD2-responsive NO, TNF-alpha, VEGF-A, and IL-12 levels was observed. Further, genome-wide microRNA expression profiling identified Ac2PIM-responsive miR-150 and miR-143 to target NOD2 signaling adaptors, RIP2 and TAK1, respectively. Interestingly, Ac2PIM was found to activate the SRC-FAK-PYK2-CREB cascade via TLR2 to recruit CBP/P300 at the promoters of miR-150 and miR-143 and epigenetically induce their expression. Loss-of-function studies utilizing specific miRNA inhibitors establish that Ac2PIM, via the miRNAs, abrogate NOD2-induced PI3K-PKC delta-MAPK pathway to suppress beta-catenin-mediated expression of COX-2, SOCS-3, and MMP-9. Our investigation has thus underscored the negative regulatory role of Ac2PIM-TLR2 signaling on NOD2 pathway which could broaden our understanding on vaccine potential or adjuvant utilities of Ac2PIM and/or MDP.

Growth rate of YBCO single grains containing Y-2411(M)

Y-Ba-Cu-O (YBCO) single grains have the potential to generate large trapped magnetic fields for a variety of engineering applications, and research on the processing and properties of this material has attracted world-wide interest. In particular, the introduction of flux pinning centres to the large grain microstructure to improve its current density, Jc, and hence trapped field, has been investigated extensively over the past decade. Y 2Ba4CuMOx [Y-2411(M)], where M = Nb, Ta, Mo, W, Ru, Zr, Bi and Ag, has been reported to form particularly effective flux pinning centres in YBCO due primarily to its ability to exist as nano-size inclusions in the superconducting phase matrix. However, the addition of the Y-2411(M) phase to the precursor composition complicates the melt-processing of single grains. We report an investigation of the growth rate of single YBCO grains containing Y-2411(Bi) phase inclusions and Y2O3. The superconducting properties of these large single grains have been measured specifically to investigate the effect of Y2O3 on broadening the growth window of these materials. © 2010 IOP Publishing Ltd.

Continuous spectrum growth and modal instability in swirling duct flow

We present results on the stability of compressible inviscid swirling flows in an annular duct. Such flows are present in aeroengines, for example in the by-pass duct, and there are also similar flows in many aeroacoustic or aeronautical applications. The linearised Euler equations have a ('critical layer') singularity associated with pure convection of the unsteady disturbance by the mean flow, and we focus our attention on this region of the spectrum. By considering the critical layer singularity, we identify the continuous spectrum of the problem and describe how it contributes to the unsteady field. We find a very generic family of instability modes near to the continuous spectrum, whose eigenvalue wavenumbers form an infinite set and accumulate to a point in the complex plane. We study this accumulation process asymptotically, and find conditions on the flow to support such instabilities. It is also found that the continuous spectrum can cause a new type of instability, leading to algebraic growth with an exponent determined by the mean flow, given in the analysis. The exponent of algebraic growth can be arbitrarily large. Numerical demonstrations of the continuous spectrum instability, and also the modal instabilities are presented.

A constitutive model for cavitation and cavity growth in rubber-like materials under arbitrary tri-axial loading

In this paper, we attempted to construct a constitutive model to deal with the phenomenon of cavitation and cavity growth in a rubber-like material subjected to an arbitrary tri-axial loading. To this end, we considered a spherical elementary representative volume in a general Rivlin's incompressible material containing a central spherical cavity. The kinematics proposed by [Hou, H.S., Abeyaratne, R., 1992. Cavitation in elastic and elastic-plastic solids. J. Mech. Phys. Solids 40, 571-722] was adopted in order to construct an approximate but optimal field. In order to establish a suitable constitutive law for this class of materials, we utilized the homogenisation technique that permits us to calculate the average strain energy density of the volume. The cavity growth was considered through a physically realistic failure criterion. Combination of the constitutive law and the failure criterion enables us to describe correctly the global behaviour and the damage evolution of the material under tri-axial loading. It was shown that the present models can efficiently reproduce different stress states, varying from uniaxial to tri-axial tensions, observed in experimentations. Comparison between predicted results and experimental data proves that the proposed model is accurate and physically reasonable. Another advantage is that the proposed model does not need special identification work, the initial Rivlin's law for the corresponding incompressible material is sufficient to form the new law for the compressible material resulted from cavitation procedure. (C) 2007 Elsevier Ltd. All rights reserved.