Actomyosin contractility rotates the cell nucleus

The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells.

Note: Design and development of an integrated three-dimensional scanner for atomic force microscopy

A compact scanning head for the Atomic Force Microscope (AFM) greatly enhances the portability of AFM and facilitates easy integration with other tools. This paper reports the design and development of a three-dimensional (3D) scanner integrated into an AFM micro-probe. The scanner is realized by means of a novel design for the AFM probe along with a magnetic actuation system. The integrated scanner, the actuation system, and their associated mechanical mounts are fabricated and evaluated. The experimentally calibrated actuation ranges are shown to be over 1 mu m along all the three axes. (c) 2013 AIP Publishing LLC.

Scientific and technological aspects of fixed bed biomass gasification

In recent years new emphasis has been placed on problems of the environmental aspects of waste disposal, especially investigating alternatives to landfill, sea dumping and incineration. There is also a strong emphasis on clean, economic and efficient processes for electric power generation. These two topics may at first appear unrelated. Nevertheless, the technological advances are now such that a solution to both can be combined in a novel approach to power generation based on waste-derived fuels, including refuse-derived fuel (RDF) and sludge power (SP) by utilising a slagging gasifier and advance fuel technology (AFT). The most appropriate gasification technique for such waste utilisation is the British Gas/Lurgi (BGL) high pressure, fixed bed slagging gasifier where operation on a range of feedstocks has been well-documented. This gasifier is particularly amenable to briquette fuel feeding and, operating in an integrated gasification combined cycle mode (IGCC), is particularly advantageous. Here, the author details how this technology has been applied to Britain's first AFT-IGCC Power Station which is now under development at Fife Energy Ltd., in Scotland, the former British Gas Westfield Development Centre.

Enzymatic degradation of polymers: a brief review

Recently, research on polymer has drawn much attention mainly due to the ever increasing application of these polymeric materials in several areas such as food packaging industry, agricultural industry and biomedical research. However, increasing industrial use of polymers has led to the environmentally critical issue of waste disposal. Further, the successful implication of polymeric materials in biomedical applications depends on the biodegradability of the concerned polymer. Various enzymes play an important role in the biodegradation of polymers. The present review describes the enzyme mediated biodegradation of various polymers including synthetic, natural and blends of these materials. Detailed examples of enzymatic degradation of polymers are illustrated from current scientific literature with the discussion on various factors that can influence the degradation. In addition, different techniques that are generally applied to assess the degradation process as well as degradation products have been described. Finally, a special emphasis is given to the investigation of the kinetics of polymer degradation by enzymes.

Raman spectroscopy explores molecular structural signatures of hidden materials in depth: Universal Multiple Angle Raman Spectroscopy

Non-invasive 3D imaging in materials and medical research involves methodologies such as X-ray imaging, MRI, fluorescence and optical coherence tomography, NIR absorption imaging, etc., providing global morphological/density/absorption changes of the hidden components. However, molecular information of such buried materials has been elusive. In this article we demonstrate observation of molecular structural information of materials hidden/buried in depth using Raman scattering. Typically, Raman spectroscopic observations are made at fixed collection angles, such as, 906, 1356, and 1806, except in spatially offset Raman scattering (SORS) (only back scattering based collection of photons) and transmission techniques. Such specific collection angles restrict the observations of Raman signals either from or near the surface of the materials. Universal Multiple Angle Raman Spectroscopy (UMARS) presented here employs the principle of (a) penetration depth of photons and then diffuse propagation through non-absorbing media by multiple scattering and (b) detection of signals from all the observable angles.

An automated pipette puller for fabrication of glass micropipettes

Glass micropipettes are versatile probing tools for performing micro-and nano-manipulation tasks. This paper presents the design and development of an automated pipette puller system for fabrication of glass micropipettes. The pipette puller employs a new strategy for fabrication of micropipettes that enables achieving independent control of their taper, tip diameter, and bend-angle, and also facilitates theoretical derivation of simple, approximate relationships between the pipette shape and the pulling parameters. Subsequently, the design and fabrication of the pipette puller is described, which include that of the pipette heating system, the mechanical motion stages, and the control electronics of the pipette puller. The fabricated pipette puller is experimentally evaluated to demonstrate control of the taper, tip diameter, and the bend-angle of the micropipette. Further, the dependence of the taper and tip diameter on the pulling parameters is evaluated and is shown to be in alignment with the proposed theoretical relationships. (C) 2014 AIP Publishing LLC.

Small molecule inhibitors of HCV replication from Pomegranate

Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and `no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

Generalized scaling of misorientation angle distributions at meso-scale in deformed materials

Scaling behaviour has been observed at mesoscopic level irrespective of crystal structure, type of boundary and operative micro-mechanisms like slip and twinning. The presence of scaling at the meso-scale accompanied with that at the nano-scale clearly demonstrates the intrinsic spanning for different deformation processes and a true universal nature of scaling. The origin of a 1/2 power law in deformation of crystalline materials in terms of misorientation proportional to square root of strain is attributed to importance of interfaces in deformation processes. It is proposed that materials existing in three dimensional Euclidean spaces accommodate plastic deformation by one dimensional dislocations and their interaction with two dimensional interfaces at different length scales. This gives rise to a 1/2 power law scaling in materials. This intrinsic relationship can be incorporated in crystal plasticity models that aim to span different length and time scales to predict the deformation response of crystalline materials accurately.

Room temperature electrical spin injection into GaAs by an oxide spin injector

Spin injection, manipulation and detection are the integral parts of spintronics devices and have attracted tremendous attention in the last decade. It is necessary to judiciously choose the right combination of materials to have compatibility with the existing semiconductor technology. Conventional metallic magnets were the first choice for injecting spins into semiconductors in the past. So far there is no success in using a magnetic oxide material for spin injection, which is very important for the development of oxide based spintronics devices. Here we demonstrate the electrical spin injection from an oxide magnetic material Fe3O4, into GaAs with the help of tunnel barrier MgO at room temperature using 3-terminal Hanle measurement technique. A spin relaxation time tau similar to 0.9 ns for n-GaAs at 300 K is observed along with expected temperature dependence of t. Spin injection using Fe3O4/MgO system is further established by injecting spins into p-GaAs and a tau of similar to 0.32 ns is obtained at 300 K. Enhancement of spin injection efficiency is seen with barrier thickness. In the field of spin injection and detection, our work using an oxide magnetic material establishes a good platform for the development of room temperature oxide based spintronics devices.

Sapodilla Plum (Achras sapota) Induces Apoptosis in Cancer Cell Lines and Inhibits Tumor Progression in Mice

Intake of fruits rich in antioxidants in daily diet is suggested to be cancer preventive. Sapota is a tropical fruit grown and consumed extensively in several countries including India and Mexico. Here we show that methanolic extracts of Sapota fruit (MESF) induces cytotoxicity in a dose-dependent manner in cancer cell lines. Cell cycle analysis suggested activation of apoptosis, without arresting cell cycle progression. Annexin V-propidium iodide double-staining demonstrated that Sapota fruit extracts potentiate apoptosis rather than necrosis in cancer cells. Loss of mitochondrial membrane potential, upregulation of proapoptotic proteins, activation of MCL-1, PARP-1, and Caspase 9 suggest that MESF treatment leads to activation of mitochondrial pathway of apoptosis. More importantly, we show that MESF treatment leads to significant inhibition of tumor growth and a 3-fold increase in the life span of tumor bearing animals compared to untreated tumor mice.

Application of lateral photovoltage towards contactless light beam induced current measurements and its dependence on the finite beam size

The nature of the signal due to light beam induced current (LBIC) at the remote contacts is verified as a lateral photovoltage for non-uniformly illuminated planar p-n junction devices; simulation and experimental results are presented. The limitations imposed by the ohmic contacts are successfully overcome by the introduction of capacitively coupled remote contacts, which yield similar results without any significant loss in the estimated material and device parameters. It is observed that the LBIC measurements introduce artefacts such as shift in peak position with increasing laser power. Simulation of LBIC signal as a function of characteristic length L-c of photo-generated carriers and for different beam diameters has resulted in the observed peak shifts, thus attributed to the finite size of the beam. Further, the idea of capacitively coupled contacts has been extended to contactless measurements using pressure contacts with an oxidized aluminium electrodes. This technique avoids the contagious sample processing steps, which may introduce unintentional defects and contaminants into the material and devices under observation. Thus, we present here, the remote contact LBIC as a practically non-destructive tool in the evaluation of device parameters and welcome its use during fabrication steps. (C) 2014 AIP Publishing LLC.

Characterizing the pocketome of Mycobacterium tuberculosis and application in rationalizing polypharmacological target selection

Polypharmacology is beginning to emerge as an important concept in the field of drug discovery. However, there are no established approaches to either select appropriate target sets or design polypharmacological drugs. Here, we propose a structural-proteomics approach that utilizes the structural information of the binding sites at a genome-scale obtained through in-house algorithms to characterize the pocketome, yielding a list of ligands that can participate in various biochemical events in the mycobacterial cell. The pocket-type space is seen to be much larger than the sequence or fold-space, suggesting that variations at the site-level contribute significantly to functional repertoire of the organism. All-pair comparisons of binding sites within Mycobacterium tuberculosis (Mtb), pocket-similarity network construction and clustering result in identification of binding-site sets, each containing a group of similar binding sites, theoretically having a potential to interact with a common set of compounds. A polypharmacology index is formulated to rank targets by incorporating a measure of druggability and similarity to other pockets within the proteome. This study presents a rational approach to identify targets with polypharmacological potential along with possible drugs for repurposing, while simultaneously, obtaining clues on lead compounds for use in new drug-discovery pipelines.

Cooling a Band Insulator with a Metal: Fermionic Superfluid in a Dimerized Holographic Lattice

A cold atomic realization of a quantum correlated state of many fermions on a lattice, eg. superfluid, has eluded experimental realization due to the entropy problem. Here we propose a route to realize such a state using holographic lattice and confining potentials. The potentials are designed to produces aband insulating state (low heat capacity) at the trap center, and a metallic state (high heat capacity) at the periphery. The metal ``cools'' the central band insulator by extracting out the excess entropy. The central band insulator can be turned into a superfluid by tuning an attractive interaction between the fermions. Crucially, the holographic lattice allows the emergent superfluid to have a high transition temperature - even twice that of the effective trap temperature. The scheme provides a promising route to a laboratory realization of a fermionic lattice superfluid, even while being adaptable to simulate other many body states.