MECHANISM OF CELL LYSIS IN MICROFLUIDIC CHANNEL WITH INTEGRATED NANOCOMPOSITE ELECTRODES

This paper reports on the characterization of an integrated micro-fluidic platform for controlled electrical lysis of biological cells and subsequent extraction of intracellular biomolecules. The proposed methodology is capable of high throughput electrical cell lysis facilitated by nano-composite coated electrodes. The nano-composites are synthesized using Carbon Nanotube and ZnO nanorod dispersion in polymer. Bacterial cells are used to demonstrate the lysis performance of these nanocomposite electrodes. Investigation of electrical lysis in the microchannel is carried out under different parameters, one with continuous DC application and the other under DC biased AC electric field. Lysis in DC field is dependent on optimal field strength and governed by the cell type. By introducing the AC electrical field, the electrokinetics is controlled to prevent cell clogging in the micro-channel and ensure uniform cell dispersion and lysis. Lysis mechanism is analyzed with time-resolved fluorescence imaging which reveal the time scale of electrical lysis and explain the dynamic behavior of GFP-expressing E. coli cells under the electric field induced by nanocomposite electrodes. The DNA and protein samples extracted after lysis are compared with those obtained from a conventional chemical lysis method by using a UV-Visible spectroscopy and fluorimetry. The paper also focuses on the mechanistic understanding of the nano-composite coating material and the film thickness on the leakage charge densities which lead to differential lysis efficiency.

Effect of hinged leaflets on vortex pair generation

We experimentally study the effect of having hinged leaflets at the jet exit on the formation of a two-dimensional counter-rotating vortex pair. A piston-cylinder mechanism is used to generate a starting jet from a high-aspect-ratio channel into a quiescent medium. For a rigid exit, with no leaflets at the channel exit, the measurements at a central plane show that the trailing jet in the present case is never detached from the vortex pair, and keeps feeding into the latter, unlike in the axisymmetric case. Passive flexibility is introduced in the form of rigid leaflets or flaps that are hinged at the exit of the channel, with the flaps initially parallel to the channel walls. The experimental arrangement closely approximates the limiting case of a free-to-rotate rigid flap with negligible structural stiffness, damping and flap inertia, as these limiting structural properties permit the largest flap openings. Using this arrangement, we start the flow and measure the flap kinematics and the vorticity fields for different flap lengths and piston velocity programs. The typical motion of the flaps involves a rapid opening and a subsequent more gradual return to its initial position, both of which occur when the piston is still moving. The initial opening of the flaps can be attributed to an excess pressure that develops in the channel when the flow starts, due to the acceleration that has to be imparted to the fluid slug between the flaps. In the case with flaps, two additional pairs of vortices are formed because of the motion of the flaps, leading to the ejection of a total of up to three vortex pairs from the hinged exit. The flaps' length (L-f) is found to significantly affect flap motions when plotted using the conventional time scale L/d, where L is the piston stroke and d is the channel width. However, with a newly defined time scale based on the flap length (L/L-f), we find a good collapse of all the measured flap motions irrespective of flap length and piston velocity for an impulsively started piston motion. The maximum opening angle in all these impulsive velocity program cases, irrespective of the flap length, is found to be close to 15 degrees. Even though the flap kinematics collapses well with L/L-f, there are differences in the distribution of the ejected vorticity even for the same L/L-f. Such a redistribution of vorticity can lead to important changes in the overall properties of the flow, and it gives us a better understanding of the importance of exit flexibility in such flows.

Metal based photosensitizers of tetradentate Schiff base: Promising role in anti-tumor activity through singlet oxygen generation mechanism

In the present investigation, a Schiff base N'(1),N'(3)-bis(Z)-(2-hydroxynapthyl)methylidene]benzene-1,3-dicarbod ihydrazide (L-1) and its Co(II), Ni(II) and Cu(II) complexes have been synthesized and characterized as novel photosensitizing agents for photodynamic therapy (PDT). The interaction of these complexes with calf thymus DNA (CT DNA) has been explored using absorption, thermal denaturation and viscometric studies. The experimental results revealed that Co(II) and Ni(II) complexes on binding to CT DNA imply a covalent mode, most possibly involving guanine N7 nitrogen of DNA, with an intrinsic binding constant K-b of 4.5 x 10(4) M-1 and 4.2 x 10(4) M-1, respectively. However, interestingly, the Cu(II) complex is involved in the surface binding to minor groove via phosphate backbone of DNA double helix with an intrinsic binding constant K-b of 5.7 x 10(4) M-1. The Co(II), Ni(II) and Cu(II) complexes are active in cleaving supercoiled (SC) pUC19 DNA on photoexposure to UV-visible light of 365 nm, through O-1(2) generation with quantum yields of 0.28, 0.25 and 0.30, respectively. Further, these complexes are cytotoxic in A549 lung cancer cells, showing an enhancement of cytotoxicity upon light irradiation. (C) 2013 Elsevier B.V. All rights reserved.

Mechanism design for time critical and cost critical task execution via crowdsourcing

An exciting application of crowdsourcing is to use social networks in complex task execution. In this paper, we address the problem of a planner who needs to incentivize agents within a network in order to seek their help in executing an atomic task as well as in recruiting other agents to execute the task. We study this mechanism design problem under two natural resource optimization settings: (1) cost critical tasks, where the planner's goal is to minimize the total cost, and (2) time critical tasks, where the goal is to minimize the total time elapsed before the task is executed. We identify a set of desirable properties that should ideally be satisfied by a crowdsourcing mechanism. In particular, sybil-proofness and collapse-proofness are two complementary properties in our desiderata. We prove that no mechanism can satisfy all the desirable properties simultaneously. This leads us naturally to explore approximate versions of the critical properties. We focus our attention on approximate sybil-proofness and our exploration leads to a parametrized family of payment mechanisms which satisfy collapse-proofness. We characterize the approximate versions of the desirable properties in cost critical and time critical domain.

A strategy-proof and budget-balanced mechanism for carbon footprint reduction by global companies

The problem addressed in this paper is concerned with an important issue faced by any green aware global company to keep its emissions within a prescribed cap. The specific problem is to allocate carbon reductions to its different divisions and supply chain partners in achieving a required target of reductions in its carbon reduction program. The problem becomes a challenging one since the divisions and supply chain partners, being autonomous, may exhibit strategic behavior. We use a standard mechanism design approach to solve this problem. While designing a mechanism for the emission reduction allocation problem, the key properties that need to be satisfied are dominant strategy incentive compatibility (DSIC) (also called strategy-proofness), strict budget balance (SBB), and allocative efficiency (AE). Mechanism design theory has shown that it is not possible to achieve the above three properties simultaneously. In the literature, a mechanism that satisfies DSIC and AE has recently been proposed in this context, keeping the budget imbalance minimal. Motivated by the observation that SBB is an important requirement, in this paper, we propose a mechanism that satisfies DSIC and SBB with slight compromise in allocative efficiency. Our experimentation with a stylized case study shows that the proposed mechanism performs satisfactorily and provides an attractive alternative mechanism for carbon footprint reduction by global companies.

Mechanism design for green, truthful procurement auctions

Auction based mechanisms have become popular in industrial procurement settings. These mechanisms minimize the cost of procurement and at the same time achieve desirable properties such as truthful bidding by the suppliers. In this paper, we investigate the design of truthful procurement auctions taking into account an additional important issue namely carbon emissions. In particular, we focus on the following procurement problem: A buyer wishes to source multiple units of a homogeneous item from several competing suppliers who offer volume discount bids and who also provide emission curves that specify the cost of emissions as a function of volume of supply. We assume that emission curves are reported truthfully since that information is easily verifiable through standard sources. First we formulate the volume discount procurement auction problem with emission constraints under the assumption that the suppliers are honest (that is they report production costs truthfully). Next we describe a mechanism design formulation for green procurement with strategic suppliers. Our numerical experimentation shows that emission constraints can significantly alter sourcing decisions and affect the procurement costs dramatically. To the best of our knowledge, this is the first effort in explicitly taking into account carbon emissions in planning procurement auctions.

TCP: thread contention predictor for parallel programs

With proliferation of chip multicores (CMPs) on desktops and embedded platforms, multi-threaded programs have become ubiquitous. Existence of multiple threads may cause resource contention, such as, in on-chip shared cache and interconnects, depending upon how they access resources. Hence, we propose a tool - Thread Contention Predictor (TCP) to help quantify the number of threads sharing data and their sharing pattern. We demonstrate its use to predict a more profitable shared, last level on-chip cache (LLC) access policy on CMPs. Our cache configuration predictor is 2.2 times faster compared to the cycle-accurate simulations. We also demonstrate its use for identifying hot data structures in a program which may cause performance degradation due to false data sharing. We fix layout of such data structures and show up-to 10% and 18% improvement in execution time and energy-delay product (EDP), respectively.

Mechanism design for cost optimal PAC learning in the presence of strategic noisy annotators

We consider the problem of Probably Ap-proximate Correct (PAC) learning of a bi-nary classifier from noisy labeled exam-ples acquired from multiple annotators(each characterized by a respective clas-sification noise rate). First, we consider the complete information scenario, where the learner knows the noise rates of all the annotators. For this scenario, we derive sample complexity bound for the Mini-mum Disagreement Algorithm (MDA) on the number of labeled examples to be ob-tained from each annotator. Next, we consider the incomplete information sce-nario, where each annotator is strategic and holds the respective noise rate as a private information. For this scenario, we design a cost optimal procurement auc-tion mechanism along the lines of Myer-son’s optimal auction design framework in a non-trivial manner. This mechanism satisfies incentive compatibility property,thereby facilitating the learner to elicit true noise rates of all the annotators.

Fast and efficient automatic memory management for GPUs using compiler-assisted runtime coherence scheme

Exploiting the performance potential of GPUs requires managing the data transfers to and from them efficiently which is an error-prone and tedious task. In this paper, we develop a software coherence mechanism to fully automate all data transfers between the CPU and GPU without any assistance from the programmer. Our mechanism uses compiler analysis to identify potential stale accesses and uses a runtime to initiate transfers as necessary. This allows us to avoid redundant transfers that are exhibited by all other existing automatic memory management proposals. We integrate our automatic memory manager into the X10 compiler and runtime, and find that it not only results in smaller and simpler programs, but also eliminates redundant memory transfers. Tested on eight programs ported from the Rodinia benchmark suite it achieves (i) a 1.06x speedup over hand-tuned manual memory management, and (ii) a 1.29x speedup over another recently proposed compiler--runtime automatic memory management system. Compared to other existing runtime-only and compiler-only proposals, it also transfers 2.2x to 13.3x less data on average.

Identification of key amino acid residues in the catalytic mechanism of diaminopropionate ammonialyase from Salmonella typhimurium

Diaminopropionate ammonialyase (DAPAL), a fold-typeII pyridoxal 5-phosphate-dependent enzyme, catalyzes the ,-elimination of diaminopropionate (DAP) to pyruvate and ammonia. DAPAL was able to utilize both d- and l-DAP as substrates with almost equal efficiency. Mutational analysis of functionally important residues such as Thr385, Asp125 and Asp194 was carried out to understand the mechanism by which the isomers are hydrolyzed. Further, the putative residues involved in the formation of disulfide bond Cys271 and Cys299 were also mutated. T385S, T385D sDAPAL were as active with dl-DAP as substrate as sDAPAL, whereas the later exhibited a threefold increase in catalytic efficiency with d-Ser as substrate. Further analysis of these mutants suggested that DAPAL might follow an anti-E-2 mechanism of catalysis that does not involve the formation of a quinonoid intermediate. Of the two mutants of Asp125, D125E showed complete loss of activity with d-DAP as substrate, whereas the reaction with l-DAP was not affected significantly, demonstrating that Asp125 was essential for abstraction of protons from the d-isomer. By contrast, mutational analysis of Asp194 showed that the residue may not be directly involved in proton abstraction from l-DAP. sDAPAL does not form a disulfide bond in solution, although the position of Cys299 and Cys271 in the modeled structure of sDAPAL favored the formation of a disulfide bond. Further, unlike eDAPAL, sDAPAL could be activated by monovalent cations. Mutation of the cysteine residues showed that Cys271 may be involved in coordinating the monovalent cation, as observed in the case of other fold-typeII enzymes.

Growth mechanism of ZnO nanostructures for ultra-high piezoelectric d(33) coefficient

A comparative morphological study of different ZnO nanostructures was carried out with different varying process parameters for energy harvesting. Molarity, temperature, growth duration and seed layer were such fundamental controlling parameters. The study brings out an outstanding piezoelectric coefficient (d(33)) of 44.33 pm/V for vertically aligned ZnO nanorod structures, considered as the highest reported d(33) value for any kind of ZnO nanostructures. XRD analysis confirms wurtzite nature of this nanorod structure with 0001] as preferential growth direction. Semiconducting characteristic of nanorods was determined with temperature induced I/V characterization.

Antithyroid drugs and their analogues: synthesis, structure, and mechanism of action

Thyroid hormones are essential for the development and differentiation of all cells of the human body. They regulate protein, fat, and carbohydrate metabolism. In this Account, we discuss the synthesis, structure, and mechanism of action of thyroid hormones and their analogues. The prohormone thyroxine (14) is synthesized on thyroglobulin by thyroid peroxidase (TPO), a heme enzyme that uses iodide and hydrogen peroxide to perform iodination and phenolic coupling reactions. The monodeiodination of T4 to 3,3',5-triiodothyronine (13) by selenium-containing deiodinases (ID-1, ID-2) is a key step in the activation of thyroid hormones. The type 3 deiodinase (ID-3) catalyzes the deactivation of thyroid hormone in a process that removes iodine selectively from the tyrosyl ring of T4 to produce 3,3',5'-triiodothyronine (rT3). Several physiological and pathological stimuli influence thyroid hormone synthesis. The overproduction of thyroid hormones leads to hyperthyroidism, which is treated by antithyroid drugs that either inhibit the thyroid hormone biosynthesis and/or decrease the conversion of T4 to T3. Antithyroid drugs are thiourea-based compounds, which indude propylthiouracil (PTU), methimazole (MM I), and carbimazole (CBZ). The thyroid gland actively concentrates these heterocyclic compounds against a concentration gradient Recently, the selenium analogues of PTU, MMI, and CBZ attracted significant attention because the selenium moiety in these compounds has a higher nucleophilicity than that of the sulfur moiety. Researchers have developed new methods for the synthesis of the selenium compounds. Several experimental and theoretical investigations revealed that the selone (C=Se) in the selenium analogues is more polarized than the thione (C=S) in the sulfur compounds, and the selones exist predominantly in their zwitterionic forms. Although the thionamide-based antithyroid drugs have been used for almost 70 years, the mechanism of their action is not completely understood. Most investigations have revealed that MMI and PTU irreversibly inhibit TPO. PTU, MTU, and their selenium analogues also inhibit ID-1, most likely by reacting with the selenenyl iodide intermediate. The good ID-1 inhibitory activity of Pill and its analogues can be ascribed to the presence of the -N(H)-C(=O)- functionality that can form hydrogen bonds with nearby amino add residues in the selenenyl sulfide state. In addition to the TPO and ID-1 inhibition, the selenium analogues are very good antioxidants. In the presence of cellular reducing agents such as GSH, these compounds catalytically reduce hydrogen peroxide. They can also efficiently scavenge peroxynitrite, a potent biological oxidant and nitrating agent.

On the Mechanism of Phase Transfer Catalysis in Brust-Schiffrin Synthesis of Metal Nanoparticles

The two-phase Brust-Schiffrin method (BSM) is used to synthesize highly stable nanoparticles of noble metals. A phase transfer catalyst (PTC) is used to bring in aqueous phase soluble precursors into the organic phase to enable particle synthesis there. Two different mechanisms for phase transfer are advanced in the literature. The first mechanism considers PTC to bring in an aqueous phase soluble precursor by complexing with it. The second mechanism considers the ionic species to be contained in inverse micelles of PTC, with a water core inside. A comprehensive experimental study involving measurement of interfacial tension, viscosity, water content by Karl-Fischer titration, static light scattering, H-1 NMR, and small-angle X-ray scattering is reported in this work to establish that the phase transfer catalyst tetraoctylammonium bromide transfers ions by complexing with them, instead of encapsulating them in inverse micelles. The findings have implications for particle synthesis in two-phase methods such as BSM and their modification to produce more monodispersed particles.

Incorporation of Interfacial Intermetallic Morphology in Fracture Mechanism Map for Sn-Ag-Cu Solder Joints

A fracture mechanism map (FMM) is a powerful tool which correlates the fracture behavior of a material to its microstructural characteristics in an explicit and convenient way. In the FMM for solder joints, an effective thickness of the interfacial intermetallic compound (IMC) layer (t (eff)) and the solder yield strength (sigma (ys,eff)) are used as abscissa and ordinate axes, respectively, as these two predominantly affect the fracture behavior of solder joints. Earlier, a definition of t (eff), based on the uniform thickness of IMC (t (u)) and the average height of the IMC scallops (t (s)), was proposed and shown to aptly explain the fracture behavior of solder joints on Cu. This paper presents a more general definition of t (eff) that is more widely applicable to a range of metallizations, including Cu and electroless nickel immersion gold (ENIG). Using this new definition of t (eff), mode I FMM for SAC387/Cu joints has been updated and its validity was confirmed. A preliminary FMM for SAC387/Cu joints with ENIG metallization is also presented.

Nestmate discrimination in the social wasp Ropalidia marginata: chemical cues and chemosensory mechanism

Nestmate discrimination plays an important role in preserving the integrity of social insect colonies. It is known to occur in the primitively eusocial wasp Ropalidia marginata in which non-nestmate conspecifics are not allowed to come near a nest. However, newly eclosed females are accepted in foreign colonies, suggesting that such individuals may not express the cues that permit differentiation between nestmates and non-nestmates. As cuticular hydrocarbons (CHCs) have been implicated as chemosensory cues used in nestmate recognition in other species, we investigated, using bioassays and chemical analyses, whether CHCs can play a role in nestmate recognition in R. marginata. We found that individuals can be differentiated according to colony membership using their CHC profiles, suggesting a role of CHCs in nestmate discrimination. Non-nestmate CHCs of adult females received more aggression than nestmate CHCs, thereby showing that CHCs are used as cues for nestmate recognition. Contrarily, and as expected, CHCs of newly eclosed females were not discriminated against when presented to a foreign colony. Behavioural sequence analysis revealed the behavioural mechanism involved in sensing nestmate recognition cues. We also found that newly eclosed females had a different CHC profile from that of adult females, thereby providing an explanation for why young females are accepted in foreign colonies. (C) 2013 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.