Curvature based mobility analysis and form closure of smooth planar curves with multiple contacts

This paper presents a simple second-order, curvature based mobility analysis of planar curves in contact. The underlying theory deals with penetration and separation of curves with multiple contacts, based on relative configuration of osculating circles at points of contact for a second-order rotation about each point of the plane. Geometric and analytical treatment of mobility analysis is presented for generic as well as special contact geometries. For objects with a single contact, partitioning of the plane into four types of mobility regions has been shown. Using point based composition operations based on dual-number matrices, analysis has been extended to computationally handle multiple contacts scenario. A novel color coded directed line has been proposed to capture the contact scenario. Multiple contacts mobility is obtained through intersection of the mobility half-spaces. It is derived that mobility region comprises a pair of unbounded or a single bounded convex polygon. The theory has been used for analysis and synthesis of form closure configurations, revolute and prismatic kinematic pairs. (C) 2013 Elsevier Ltd. All rights reserved.

RNA-dependent RNA polymerase of Japanese encephalitis virus binds the initiator nucleotide GTP to form a mechanistically important pre-initiation state

Flaviviral RNA-dependent RNA polymerases (RdRps) initiate replication of the single-stranded RNA genome in the absence of a primer. The template sequence 5'-CU-3' at the 3'-end of the flaviviral genome is highly conserved. Surprisingly, flaviviral RdRps require high concentrations of the second incoming nucleotide GTP to catalyze de novo template-dependent RNA synthesis. We show that GTP stimulates de novo RNA synthesis by RdRp from Japanese encephalitis virus (jRdRp) also. Crystal structures of jRdRp complexed with GTP and ATP provide a basis for specific recognition of GTP. Comparison of the jRdRp(GTP) structure with other viral RdRp-GTP structures shows that GTP binds jRdRp in a novel conformation. Apo-jRdRp structure suggests that the conserved motif F of jRdRp occupies multiple conformations in absence of GTP. Motif F becomes ordered on GTP binding and occludes the nucleotide triphosphate entry tunnel. Mutational analysis of key residues that interact with GTP evinces that the jRdRp(GTP) structure represents a novel pre-initiation state. Also, binding studies show that GTP binding reduces affinity of RdRp for RNA, but the presence of the catalytic Mn2+ ion abolishes this inhibition. Collectively, these observations suggest that the observed pre-initiation state may serve as a check-point to prevent erroneous template-independent RNA synthesis by jRdRp during initiation.

Analytical Closed-Form Expressions for Harmonic Distortion Corresponding to Novel Switching Sequences for Neutral-Point-Clamped Inverters

Analytical closed-form expressions for harmonic distortion factors corresponding to various pulsewidth modulation (PWM) techniques for a two-level inverter have been reported in the literature. This paper derives such analytical closed-form expressions, pertaining to centered space-vector PWM (CSVPWM) and eight different advanced bus-clamping PWM (ABCPWM) schemes, for a three-level neutral-point-clamped (NPC) inverter. These ABCPWM schemes switch each phase at twice the nominal switching frequency in certain intervals of the line cycle while clamping each phase to one of the dc terminals over certain other intervals. The harmonic spectra of the output voltages, corresponding to the eight ABCPWM schemes, are studied and compared experimentally with that of CSVPWM over the entire modulation range. The measured values of weighted total harmonic distortion (WTHD) of the line voltage V-WTHD are used to validate the analytical closed-form expressions derived. The analytical expressions, pertaining to two of the ABCPWM methods, are also validated by measuring the total harmonic distortion (THD) in the line current I-THD on a 2.2-kW constant volts-per-hertz induction motor drive.

Study of ground state phases for spin-1/2 Falicov-Kimball model on a triangular lattice

The spin dependent Falicov-Kimball model (FKM) is studied on a triangular lattice using numerical diagonalization technique and Monte-Carlo simulation algorithm. Magnetic properties have been explored for different values of parameters: on-site Coulomb correlation U, exchange interaction J and filling of electrons. We have found that the ground state configurations exhibit long range Neel order, ferromagnetism or a mixture of both as J is varied. The magnetic moments of itinerant (d) and localized U) electrons are also studied. For the one-fourth filling case we found no magnetic moment from d- and f-electrons for U less than a critical value. `.2014 Elsevier Ltd. All rights reserved.

Propensity to Form Amyloid Fibrils Is Encoded as Excitations in the Free Energy Landscape of Monomeric Proteins

Protein aggregation, linked to many of diseases, is initiated when monomers access rogue conformations that are poised to form amyloid fibrils. We show, using simulations of src SH3 domain, that mechanical force enhances the population of the aggregation-prone (N*) states, which are rarely populated under force free native conditions but are encoded in the spectrum of native fluctuations. The folding phase diagrams of SH3 as a function of denaturant concentration (C]), mechanical force (f), and temperature exhibit an apparent two-state behavior, without revealing the presence of the elusive N* states. Interestingly, the phase boundaries separating the folded and unfolded states at all C] and f fall on a master curve, which can be quantitatively described using an analogy to superconductors in a magnetic field. The free energy profiles as a function of the molecular extension (R), which are accessible in pulling experiments, (R), reveal the presence of a native-like N* with a disordered solvent-exposed amino-terminal beta-strand. The structure of the N* state is identical with that found in Fyn SH3 by NMR dispersion experiments. We show that the timescale for fibril formation can be estimated from the population of the N* state, determined by the free energy gap separating the native structure and the N* state, a finding that can be used to assess fibril forming tendencies of proteins. The structures of the N* state are used to show that oligomer formation and likely route to fibrils occur by a domain-swap mechanism in SH3 domain. (C) 2014 Elsevier Ltd. All rights reserved.

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.

Spinning strings and minimal surfaces in AdS(3) with mixed 3-form fluxes

Motivated by the recent proposal for the S-matrix in AdS(3) x S-3 with mixed three form fluxes, we study classical folded string spinning in AdS(3) with both Ramond and Neveu-Schwarz three form fluxes. We solve the equations of motion of these strings and obtain their dispersion relation to the leading order in the Neveu-Schwarz flux b. We show that dispersion relation for the spinning strings with large spin S acquires a term given by -root lambda/2 pi b(2) log(2) S in addition to the usual root lambda/pi log S term where root lambda is proportional to the square of the radius of AdS(3). Using SO(2, 2) transformations and re-parmetrizations we show that these spinning strings can be related to light like Wilson loops in AdS(3) with Neveu-Schwarz flux b. We observe that the logarithmic divergence in the area of the light like Wilson loop is also deformed by precisely the same coefficient of the b(2) log(2) S term in the dispersion relation of the spinning string. This result indicates that the coefficient of b(2) log(2) S has a property similar to the coefficient of the log S term, known as cusp-anomalous dimension, and can possibly be determined to all orders in the coupling lambda using the recent proposal for the S-matrix.

Modal tailoring and closed-form solutions for rotating non-uniform Euler-Bernoulli beams

In this paper, the free vibration of a rotating Euler-Bernoulli beam is studied using an inverse problem approach. We assume a polynomial mode shape function for a particular mode, which satisfies all the four boundary conditions of a rotating beam, along with the internal nodes. Using this assumed mode shape function, we determine the linear mass and fifth order stiffness variations of the beam which are typical of helicopter blades. Thus, it is found that an infinite number of such beams exist whose fourth order governing differential equation possess a closed form solution for certain polynomial variations of the mass and stiffness, for both cantilever and pinned-free boundary conditions corresponding to hingeless and articulated rotors, respectively. A detailed study is conducted for the first, second and third modes of a rotating cantilever beam and the first and second elastic modes of a rotating pinned-free beam, and on how to pre-select the internal nodes such that the closed-form solutions exist for these cases. The derived results can be used as benchmark solutions for the validation of rotating beam numerical methods and may also guide nodal tailoring. (C) 2014 Elsevier Ltd. All rights reserved.

Matrix-Assisted Refolding, Purification and Activity Assessment Using a `Form Invariant' Assay for Matrix Metalloproteinase 2 (MMP2)

Matrix metalloproteinases expression is used as biomarker for various cancers and associated malignancies. Since these proteinases can cleave many intracellular proteins, overexpression tends to be toxic; hence, a challenge to purify them. To overcome these limitations, we designed a protocol where full length pro-MMP2 enzyme was overexpressed in E. coli as inclusion bodies and purified using 6xHis affinity chromatography under denaturing conditions. In one step, the enzyme was purified and refolded directly on the affinity matrix under redox conditions to obtain a bioactive protein. The pro-MMP2 protein was characterized by mass spectrometry, CD spectroscopy, zymography and activity analysis using a simple in-house developed `form invariant' assay, which reports the total MMP2 activity independent of its various forms. The methodology yielded higher yields of bioactive protein compared to other strategies reported till date, and we anticipate that using the protocol, other toxic proteins can also be overexpressed and purified from E. coli and subsequently refolded into active form using a one step renaturation protocol.

Constraints on the omega pi form factor from analyticity and unitarity

Motivated by the discrepancies noted recently between the theoretical calculations of the electromagnetic omega pi form factor and certain experimental data, we investigate this form factor using analyticity and unitarity in a framework known as the method of unitarity bounds. We use a QCD correlator computed on the spacelike axis by operator product expansion and perturbative QCD as input, and exploit unitarity and the positivity of its spectral function, including the two-pion contribution that can be reliably calculated using high-precision data on the pion form factor. From this information, we derive upper and lower bounds on the modulus of the omega pi form factor in the elastic region. The results provide a significant check on those obtained with standard dispersion relations, confirming the existence of a disagreement with experimental data in the region around 0.6 GeV.

Mycobacterium tuberculosis Cell Division Protein, FtsE, is an ATPase in Dimeric Form

FtsE is one of the earliest cell division proteins that assembles along with FtsX at the mid-cell site during cell division in Escherichia coli. Both these proteins are highly conserved across diverse bacterial genera and are predicted to constitute an ABC transporter type complex, in which FtsE is predicted to bind ATP and hydrolyse it, and FtsX is predicted to be an integral membrane protein. We had earlier reported that the MtFtsE of the human pathogen, Mycobacterium tuberculosis, binds ATP and interacts with MtFtsX on the cell membrane of M. tuberculosis and E. coli. In this study, we demonstrate that MtFtsE is an ATPase, the active form of which is a dimer, wherein the participating monomers are held together by non-covalent interactions, with the Cys84 of each monomer present at the dimer interface. Under oxidising environment, the dimer gets stabilised by the formation of Cys84-Cys84 disulphide bond. While the recombinant MtFtsE forms a dimer on the membrane of E. coli, the native MtFtsE seems to be in a different conformation in the M. tuberculosis membrane. Although disulphide bridges were not observed on the cytoplasmic side (reducing environment) of the membrane, the two participating monomers could be isolated as dimers held together by non-covalent interactions. Taken together, these findings show that MtFtsE is an ATPase in the non-covalent dimer form, with the Cys84 of each monomer present in the reduced form at the dimer interface, without participating in the dimerisation or the catalytic activity of the protein.

Context dependent non canonical WNT signaling mediates activation of fibroblasts by transforming growth factor-beta

Actions of transforming growth factor-beta are largely context dependent. For instance, TGF-beta is growth inhibitory to epithelial cells and many tumor cell-lines while it stimulates the growth of mesenchymal cells. TGF-beta also activates fibroblast cells to a myofibroblastic phenotype. In order to understand how the responsiveness of fibroblasts to TGF-beta would change in the context of transformation, we have compared the differential gene regulation by TGF-beta in immortal fibroblasts (hFhTERT), transformed fibroblasts (hFhTERT-LTgRAS) and a human fibrosarcoma cell-line (HT1080). The analysis revealed regulation of 6735, 4163, and 3478 probe-sets by TGF-beta in hFhTERT, hFhTERT-LTgRAS and HT1080 cells respectively. Intriguingly, 5291 probe-sets were found to be either regulated in hFhTERT or hFhTERT-LTgRAS cells while 2274 probe-sets were regulated either in hFhTERT or HT1080 cells suggesting that the response of immortal hFhTERT cells to TGF-beta is vastly different compared to the response of both the transformed cells hFhTERT-LTgRAS and HT1080 to TGF-beta. Strikingly, WNT pathway showed enrichment in the hFhTERT cells in Gene Set Enrichment Analysis. Functional studies showed induction of WNT4 by TGF-beta in hFhTERT cells and TGF-beta conferred action of these cells was mediated by WNT4. While TGF-beta activated both canonical and non-canonical WNT pathways in hFhTERT cells, Erk1/2 and p38 Mitogen Activated Protein Kinase pathways were activated in hFhTERT-LTgRAS and HT1080 cells. This suggests that transformation of immortal hFhTERT cells by SV40 large T antigen and activated RAS caused a switch in their response to TGF-beta which matched with the response of HT1080 cells to TGF-beta. These data suggest context dependent activation of non-canonical signaling by TGF-beta. (C) 2015 Published by Elsevier Inc.

The crystal structure of a lectin from Butea monosperma: Insight into its glycosylation and binding of ligands

Crystal structure of a lectin purified from Butea monosperma seeds was determined by Molecular Replacement method. Its primary structure was determined by Tandem Mass Spectroscopy and electron density maps from X-ray diffraction data. Its quaternary structure was tetrameric, formed of two monomers, alpha and beta, beta appearing as truncated alpha. The occurrence of two tetramers in the asymmetric unit of the crystal might be a consequence of asymmetric contacts due to difference in glycosylation and variable loops structures, to form an `octamer-structure'. The crystal structure showed binding pockets for gamma Abu, having a proposed role in plant defense, at the interface of canonical dimer-partners. Hemagglutination studies, enzyme kinetics, isothermal titration calorimetry and molecular dynamics showed that the lectin is specific to N-acetyl D-galactosamine, galactose and lactose in decreasing order, and alpha-amylase inhibitor. (C) 2014 Elsevier B.V. All rights reserved.

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.

Effect of Channel Confinement on Mixed Convective Flow Past an Equilateral Triangular Cylinder

The present work investigates the mixed convective flow and heat transfer characteristics past a triangular cylinder placed symmetrically in a vertical channel. At a representative Reynolds number, Re = 100, simulations are carried out for the blockage ratios beta = 1/3; 1/4; and 1/6. Effect of aiding and opposing buoyancy is brought about by varying the Richardson number in the range -1.0 <= Ri <= 1.0. At a blockage ratio of 1/3, suppression of vortex shedding is found at Ri = 1, whereas von Karman vortex street is seen both at beta = 1/4 and 1/6, respectively. This is the first time that such behavior of blockage ratio past a triangular cylinder in the present flow configuration is reported. Drag coefficient increases progressively with increasing Ri and a slightly higher value is noticed at beta = 1/3. For all b, heat transfer increases with increasing Ri. Flattening of Nu(avg)-Ri curve beyond Ri > 0: 75 is observed at beta = 1/3.