Dual enzyme responsive microcapsules simulating an ``OR'' logic gate for biologically triggered drug delivery applications

Hollow microcapsules capable of disintegrating in response to dual biological stimuli have been synthesized from two FDA approved drug molecules. The capsules fabricated from protamine and chondroitin sulphate disintegrate in the presence of either trypsin or hyaluronidase enzymes, which are documented to be simultaneously over-expressed under some pathological conditions.

Data Fusion of Dual Foot-Mounted INS to Reduce the Systematic Heading Drift

In this report, we investigate the problem of applying a range constraint in order to reduce the systematic heading drift in a foot-mounted inertial navigation system (INS) (motion-tracking). We make use of two foot-mounted INS, one on each foot, which are aided with zero-velocity detectors. A novel algorithm is proposed in order to reduce the systematic heading drift. The proposed algorithm is based on the idea that the separation between the two feet at any given instance must always lie within a sphere of radius equal to the maximum possible spatial separation between the two feet. A Kalman filter, getting one measurement update and two observation updates is used in this algorithm.

Joint Antenna Selection and Frequency-Domain Scheduling in OFDMA Systems with Imperfect Estimates from Dual Pilot Training Scheme

Transmit antenna selection (AS) has been adopted in contemporary wideband wireless standards such as Long Term Evolution (LTE). We analyze a comprehensive new model for AS that captures several key features about its operation in wideband orthogonal frequency division multiple access (OFDMA) systems. These include the use of channel-aware frequency-domain scheduling (FDS) in conjunction with AS, the hardware constraint that a user must transmit using the same antenna over all its assigned subcarriers, and the scheduling constraint that the subcarriers assigned to a user must be contiguous. The model also captures the novel dual pilot training scheme that is used in LTE, in which a coarse system bandwidth-wide sounding reference signal is used to acquire relatively noisy channel state information (CSI) for AS and FDS, and a dense narrow-band demodulation reference signal is used to acquire accurate CSI for data demodulation. We analyze the symbol error probability when AS is done in conjunction with the channel-unaware, but fair, round-robin scheduling and with channel-aware greedy FDS. Our results quantify how effective joint AS-FDS is in dispersive environments, the interactions between the above features, and the ability of the user to lower SRS power with minimal performance degradation.

Generation of Ligand Specificity and Modes of Oligomerization in beta-Prism I Fold Lectins

beta-Prism I fold lectins constitute one of the five widely occurring structural classes of plant lectins. Each single domain subunit is made up of three Greek key motifs arranged in a threefold symmetric fashion. The threefold symmetry is not reflected in the sequence except in the case of the lectin from banana, a monocot, which carries two sugar-binding sites instead of the one in other lectins of known three-dimensional structure, all from dicots. This is believed to be a consequence of the different evolutionary paths followed by the lectin in monocots and dicots. The galactose-specific lectins among them have two chains produced by posttranslational proteolysis and contain three aromatic residues at the binding site. The extended binding sites of galactose- and mannose-specific lectins have been thoroughly characterized. Ligand binding at the sites involves both conformational selection and induced fit. Molecular plasticity of some of the lectins in the family has been characterized. The plasticity appears to be such as to promote variability in quaternary association which could be dimeric, tetrameric, or octameric. Structural and evolutionary reasons for the variability have been explored, and the relation of oligomerization to ligand binding and conformational selection investigated.

The dual role of Zn-acid medium for one-step rapid synthesis of M@rGO (M = Au, Pt, Pd and Ag) hybrid nanostructures at room temperature

We report a new protocol for the synthesis of M@rGO (M = Au, Pt, Pd, Ag and rGO = reduced graphene oxide) hybrid nanostructures at room temperature in Zn-acid medium. The roles of Zn-acid are to reduce the GO by generated hydrogen and the deposition of metal nanoparticles on rGO by galvanic replacement reaction between Zn and Mn+.

Variants of waters’ dual system primitives using asymmetric pairings

Waters, in 2009, introduced an important technique, called dual system encryption, to construct identity-based encryption (IBE) and related schemes. The resulting IBE scheme was described in the setting of symmetric pairing. A key feature of the construction is the presence of random tags in the ciphertext and decryption key. Later work by Lewko and Waters removed the tags and proceeding through composite-order pairings led to a more efficient dual system IBE scheme using asymmetric pairings whose security is based on non-standard but static assumptions. In this work, we have systematically simplified Waters 2009 IBE scheme in the setting of asymmetric pairing. The simplifications retain tags used in the original description. This leads to several variants, the first one of which is based on standard assumptions and in comparison to Waters’ original scheme reduces ciphertexts and keys by two elements each. Going through several stages of simplifications, we finally obtain a simple scheme whose security can be based on two standard assumptions and a natural and minimal extension of the decision Diffie-Hellman problem for asymmetric pairing groups. The scheme itself is also minimal in the sense that apart from the tags, both encryption and key generation use exactly one randomiser each. This final scheme is more efficient than both the previous dual system IBE scheme in the asymmetric setting due to Lewko and Waters and the more recent dual system IBE scheme due to Lewko. We extend the IBE scheme to hierarchical IBE (HIBE) and broadcast encryption (BE) schemes. Both primitives are secure in their respective full models and have better efficiencies compared to previously known schemes offering the same level and type of security.

Multi-port network modeling of stub loaded Microstrip ring antenna for dual-band operations

A square ring microstrip antenna can be modified for dual-band operations by appropriately attaching an open ended stub. The input impedance of this antenna is analyzed here using multi-port network modeling (MNM) approach. The coupled feed is included by defining additional terms in the model. A prototype antenna is fabricated and tested to validate these computations.

Increasing cleavage specificity and activity of restriction endonuclease KpnI

Restriction enzyme KpnI is a HNH superfamily endonuclease requiring divalent metal ions for DNA cleavage but not for binding. The active site of KpnI can accommodate metal ions of different atomic radii for DNA cleavage. Although Mg2+ ion higher than 500 mu M mediates promiscuous activity, Ca2+ suppresses the promiscuity and induces high cleavage fidelity. Here, we report that a conservative mutation of the metal-coordinating residue D148 to Glu results in the elimination of the Ca2+-mediated cleavage but imparting high cleavage fidelity with Mg2+. High cleavage fidelity of the mutant D148E is achieved through better discrimination of the target site at the binding and cleavage steps. Biochemical experiments and molecular dynamics simulations suggest that the mutation inhibits Ca2+-mediated cleavage activity by altering the geometry of the Ca2+-bound HNH active site. Although the D148E mutant reduces the specific activity of the enzyme, we identified a suppressor mutation that increases the turnover rate to restore the specific activity of the high fidelity mutant to the wild-type level. Our results show that active site plasticity in coordinating different metal ions is related to KpnI promiscuous activity, and tinkering the metal ion coordination is a plausible way to reduce promiscuous activity of metalloenzymes.

Functional specificity among yeast mitochondrial Hsp70s paralogs and orthologs

The evolutionary diversity of the HSP70 gene family at the genetic level has generated complex structural variations leading to altered functional specificity and mode of regulation in different cellular compartments. By utilizing Saccharomyces cerevisiae as a model system for better understanding the global functional cooperativity between Hsp70 paralogs, we have dissected the differences in functional properties at the biochemical level between mitochondrial heat shock protein 70 (mtHsp70) Ssc1 and an uncharacterized Ssc3 paralog. Based on the evolutionary origin of Ssc3 and a high degree of sequence homology with Ssc1, it has been proposed that both have a close functional overlap in the mitochondrial matrix. Surprisingly, our results demonstrate that there is no functional cross-talk between Ssc1 and Ssc3 paralogs. The lack of in vivo functional overlap is due to altered conformation and significant lower stability associated with Ssc3. The substrate-binding domain of Ssc3 showed poor affinity toward mitochondrial client proteins and Tim44 due to the open conformation in ADP-bound state. In addition to that, the nucleotide-binding domain of Ssc3 showed an altered regulation by the Mge1 co-chaperone due to a high degree of conformational plasticity, which strongly promotes aggregation. Besides, Ssc3 possesses a dysfunctional inter-domain interface thus rendering it unable to perform functions similar to generic Hsp70s. Moreover, we have identified the critical amino acid sequence of Ssc1 and Ssc3 that can “make or break” mtHsp70 chaperone function. Together, our analysis provides the first evidence to show that the nucleotide-binding domain of mtHsp70s plays a critical role in determining the functional specificity among paralogs and orthologs across kingdoms.

Sliding mode control based terminal impact angle constrained guidance laws using dual sliding surfaces

In this paper, sliding mode control theory based guidance laws to intercept non-maneuvering targets at a desired impact angle are presented. The desired impact angle, defined in terms of a desired line-of-sight (LOS) angle, is achieved by selecting the missile's lateral acceleration (latax) to enforce sliding mode on a sliding surface based on this LOS angle. As will be shown, this guidance law does not ensure interception for all states of the missile and the target during the engagement. Hence, to satisfy the requirement of interception at the desired impact angle, a second sliding surface is designed and a switching logic, based on the conditions necessary for interception, is presented that allows the latax to switch between enforcing sliding mode on one of these surfaces so that the target can be intercepted at the desired impact angle. The guidance laws are designed using non-linear engagement dynamics.

Compact in-plane dual-axis spring-steel accelerometer

Presented in this paper is an improvement over a spring-steel dual-axis accelerometer that we had reported earlier.The fabrication process (which entails wire-cut electro discharge machining of easily accessible and inexpensive spring-steelfoil) and the sensing of the displacement (which is done using off-the-shelf Hall-effect sensors) remain the same. Theimprovements reported here are twofold: (i) the footprint of the packaged accelerometer is reduced from 80 mm square to 40mm square, and (ii) almost perfect de-coupling and symmetry are achieved between the two in-plane axes of the packageddevice as opposed to the previous embodiment where this was not the case. Good linearity with about 40 mV/g was measuredalong both the in-plane axes over a range of 0.1 to 1 g. The first two natural frequencies of the devices are at 30 Hz and 100Hz, respectively, as per the experiment. The highlights of this work are cost-effective processing, easy integration of the Hall-effect sensing capability on a customised printed circuit board, and inexpensive packaging without overly compromising eitherthe overall size or the sensitivity of the accelerometer. Through this work, we have reaffirmed the practicability of spring-steelaccelerometers towards the eventual goal of making it compete with micro machined silicon accelerometers in terms of sizeand performance. The cost is likely to be much lower for the spring-steel accelerometers than that of silicon accelerometers, especially when the volume of production is low and the sensor is to be used as a single packaged unit.

Triarylborane-dipyrromethane conjugates bearing dual receptor sites: the synthesis and evaluation of the anion binding site preference

The synthesis and optical properties of four new triarylborane-dipyrromethane (TAB-DPM) conjugates (3a-d) containing dual binding sites (hydrogen bond donor and Lewis acid) have been reported. The new compounds exhibit a selective fluorogenic response towards the F-ion. The NMR titrations show that the anions bind to the TAB-DPM conjugates via the Lewis acidic triarylborane centre in preference to the hydrogen bond donor (dipyrromethane) units.

Specific Sequence of a Beta Turn in Human La Protein May Contribute to Species Specificity of Hepatitis C Virus

Human La protein is known to be an essential host factor for translation and replication of hepatitis C virus (HCV) RNA. Previously, we have demonstrated that residues responsible for interaction of human La protein with the HCV internal ribosomal entry site (IRES) around the initiator AUG within stem-loop IV form a beta-turn in the RNA recognition motif (RRM) structure. In this study, sequence alignment and mutagenesis suggest that the HCV RNA-interacting beta-turn is conserved only in humans and chimpanzees, the species primarily known to be infected by HCV. A 7-mer peptide corresponding to the HCV RNA-interacting region of human La inhibits HCV translation, whereas another peptide corresponding to the mouse La sequence was unable to do so. Furthermore, IRES-mediated translation was found to be significantly high in the presence of recombinant human La protein in vitro in rabbit reticulocyte lysate. We observed enhanced replication with HCV subgenomic and full-length replicons upon overexpression of either human La protein or a chimeric mouse La protein harboring a human La beta-turn sequence in mouse cells. Taken together, our results raise the possibility of creating an immunocompetent HCV mouse model using human-specific cell entry factors and a humanized form of La protein.

Dual Binding Site Assisted Chromogenic and Fluorogenic Recognition and Discrimination of Fluoride and Cyanide by a Peripherally Borylated Metalloporphyrin: Overcoming Anion Interference in Organoboron Based Sensors

Peripherally triarylborane decorated porphyrin (2) and its Zn(II) complex (3) have been synthesized. Compound 3 contains of two different Lewis acidic binding sites (Zn(II) and boron center). Unlike all previously known triarylborane based sensors, the optical responses of 3 toward fluoride and cyanide are distinctively different, thus enabling the discrimination of these two interfering anions. Metalloporphyrin 3 shows a multiple channel fluorogenic response toward fluoride and cyanide and also a selective visual colorimetric response toward cyanide. By comparison with model systems and from detailed photophysical studies on 2 and 3, we conclude that the preferential binding of fluoride occurs at the peripheral borane moieties resulting in the cessation of the EET (electronic energy transfer) process from borane to porphyrin core and with negligible negetive cooperative effects. On the other hand, cyanide binding occurs at the Zn(II) core leading to drastic changes in its absorption behavior which can be followed by the naked eye. Such changes are not observed when the boryl substituent is absent (e.g., Zn-TPP and TPP). Compounds 2 and 3 were also found to be capable of extracting fluoride from aqueous medium.

Comparative Study of Protein Unfolding in Aqueous Urea and Dimethyl Sulfoxide Solutions: Surface Polarity, Solvent Specificity, and Sequence of Secondary Structure Melting

Elucidation of possible pathways between folded (native) and unfolded states of a protein is a challenging task, as the intermediates are often hard to detect. Here, we alter the solvent environment in a controlled manner by choosing two different cosolvents of water, urea, and dimethyl sulfoxide (DMSO) and study unfolding of four different proteins to understand the respective sequence of melting by computer simulation methods. We indeed find interesting differences in the sequence of melting of alpha helices and beta sheets in these two solvents. For example, in 8 M urea solution, beta-sheet parts of a protein are found to unfold preferentially, followed by the unfolding of alpha helices. In contrast, 8 M DMSO solution unfolds alpha helices first, followed by the separation of beta sheets for the majority of proteins. Sequence of unfolding events in four different alpha/beta proteins and also in chicken villin head piece (HP-36) both in urea and DMSO solutions demonstrate that the unfolding pathways are determined jointly by relative exposure of polar and nonpolar residues of a protein and the mode of molecular action of a solvent on that protein.