A comparative study of room temperature ferromagnetism in MgO films deposited by rf/dc sputtering using high purity Mg and MgO targets

Thin films of nanocrystalline MgO were deposited on glass/Si substrates by rf/dc sputtering from metallic Mg, and ceramic MgO targets. The purpose of this study is to identify the differences in the properties, magnetic in particular, of MgO films obtained on sputter deposition from 99.99% pure metallic Mg target in a controlled Nitrogen + Oxygen partial pressure (O(2)pp)] atmosphere as against those deposited using an equally pure ceramic MgO target in argon + identical oxygen ambience conditions while maintaining the same total pressure in the chamber in both cases. Characterization of the films was carried out by X-ray diffraction, focussed ion beam cross sectioning, atomic force microscopy and SQUID-magnetometry. The `as-obtained' films from pure Mg target are found to be predominantly X-ray amorphous, while the ceramic MgO target gives crystalline films, (002) oriented with respect to the film plane. The films consisted of nano-crystalline grains of size in the range of about 0.4 to 4.15 nm with the films from metallic target being more homogeneous and consisting of mostly subnanometer grains. Both the types of films are found to be ferromagnetic to much above room temperature. We observe unusually high maximum saturation magnetization (MS) values of 13.75 emu/g and similar to 4.2 emu/g, respectively for the MgO films prepared from Mg, and MgO targets. The origin of magnetism in MgO films is attributed to Mg vacancy (V-Mg), and 2p holes localized on oxygen sites. The role of nitrogen in enhancing the magnetic moments is also discussed.

Three dimensional PN based impact angle control for higher speed nonmaneuvering targets

Terminal impact angle control is crucial for enhancement of warhead effectiveness. In the literature, this problem has been addressed in the context of targets with lower speeds than the interceptor. However, in the current defence scenario, targets of much higher speed than the interceptor is a reality. This paper presents a generic proportional navigation (PN) based guidance law, that uses the standard PN and novel Retro-PN guidance laws based on the initial engagement geometry and terminal engagement requirements, for three dimensional engagement scenario against higher speed nonmaneuvering targets to control terminal impact angle. Results are obtained on the set of achievable impact angles and conditions on the navigation constant to achieve them. Simulation results are given to support the theoretical findings.

Non-singular terminal sliding mode guidance and control with terminal angle constraints for non-maneuvering targets

In this paper guidance laws to intercept stationary and constant velocity targets at a desired impact angle, based on sliding mode control theory, are proposed. The desired impact angle, which is defined in terms of a desired line-of-sight (LOS) angle, is achieved in finite time by selecting the missile's lateral acceleration (latax) to enforce non-singular terminal sliding mode on a switching surface designed using this desired LOS angle and based on non-linear engagement dynamics. Numerical simulation results are presented to validate the proposed guidance laws for different initial engagement geometries and impact angles.

Impact angle constraint guidance law using cubic splines for intercepting stationary targets

In this paper the cubic spline guidance law is presented for intercepting a stationary target at a desired impact angle. The guidance law is obtained from cubic spline curve based trajectory using an inverse method. The cubic spline t rajectory curve expresses the altitude as a cubic polynomial of the downrange. The guidance law is modified to achieve interception in the cases where impact angle is greater that or equal to 90◦. The guidance law is implemented in a feedback mode to maintain the desired impact angle and to reduce miss distance in the presence of lateral acceleration saturation and atmospheric distur- bances. The simulation results show that the guidance law fulfills all the requirements.

Corticosterone targets distinct steps of synaptic transmission via concentration specific activation of mineralocorticoid and glucocorticoid receptors

Hippocampal neurons are affected by chronic stress and have a high density of cytoplasmic mineralocorticoid and glucocorticoid receptors (MR and GR). Detailed studies on the genomic effects of the stress hormone corticosterone at physiologically relevant concentrations on different steps in synaptic transmission are limited. In this study, we tried to delineate how activation of MR and GR by different concentrations of corticosterone affects synaptic transmission at various levels. The effect of 3-h corticosterone (25, 50, and 100nM) treatment on depolarization-mediated calcium influx, vesicular release and properties of miniature excitatory post-synaptic currents (mEPSCs) were studied in cultured hippocampal neurons. Activation of MR with 25nM corticosterone treatment resulted in enhanced depolarization-mediated calcium influx via a transcription-dependent process and increased frequency of mEPSCs with larger amplitude. On the other hand, activation of GR upon 100nM corticosterone treatment resulted in increase in the rate of vesicular release via the genomic actions of GR. Furthermore, GR activation led to significant increase in the frequency of mEPSCs with larger amplitude and faster decay. Our studies indicate that differential activation of the dual receptor system of MR and GR by corticosterone targets the steps in synaptic transmission differently.

Partial Integrated Guidance and Control of Interceptors for High-Speed Ballistic Targets

A new partial integrated guidance and control design approach is proposed in this paper, which combines the benefits of both integrated guidance and control as well as the conventional guidance and control design philosophies. The proposed technique essentially operates in a two-loop structure. In the outer loop, an optimal guidance problem is formulated considering the nonlinear six degrees-of-freedom equation of motion of the interceptor. From this loop, the required pitch and yaw rates are generated by solving a nonlinear suboptimal guidance formulation in a computationally efficient manner while simultaneously assuring roll stabilization. Next, the inner loop tracks these outer loop body rate commands. This manipulation of the six degrees-of-freedom dynamics in both loops preserves the inherent time scale separation property between the translational and rotational dynamics, while retaining the philosophy of integrated guidance and control design as well. Because of this, the tuning process is quite straightforward and nontedious as well. Extensive six degrees-of-freedom simulations studies have been carried out, considering three-dimensional engagement geometry, to demonstrate the effectiveness of the proposed new design approach engaging high-speed ballistic targets. A variety of comparison studies have also been carried out to demonstrate the effectiveness of the proposed approach.

Generalized State Estimation and Model Predictive Guidance for Spiraling and Ballistic Targets

An extended Kalman filter based generalized state estimation approach is presented in this paper for accurately estimating the states of incoming high-speed targets such as ballistic missiles. A key advantage of this nine-state problem formulation is that it is very much generic and can capture spiraling as well as pure ballistic motion of targets without any change of the target model and the tuning parameters. A new nonlinear model predictive zero-effort-miss based guidance algorithm is also presented in this paper, in which both the zero-effort-miss as well as the time-to-go are predicted more accurately by first propagating the nonlinear target model (with estimated states) and zero-effort interceptor model simultaneously. This information is then used for computing the necessary lateral acceleration. Extensive six-degrees-of-freedom simulation experiments, which include noisy seeker measurements, a nonlinear dynamic inversion based autopilot for the interceptor along with appropriate actuator and sensor models and magnitude and rate saturation limits for the fin deflections, show that near-zero miss distance (i.e., hit-to-kill level performance) can be obtained when these two new techniques are applied together. Comparison studies with an augmented proportional navigation based guidance shows that the proposed model predictive guidance leads to a substantial amount of conservation in the control energy as well.

Evaluating methane storage targets: from powder samples to onboard storage systems

The development of a viable adsorbed natural gas onboard fuel system involves synthesizing materials that meet specific storage target requirements. We assess the impact on natural gas storage due to intermediate processes involved in taking a laboratory powder sample to an onboard packed or adsorbent bed module. We illustrate that reporting the V/V (volume of gas/volume of container) capacities based on powder adsorption data without accounting for losses due to pelletization and bed porosity, grossly overestimates the working storage capacity for a given material. Using data typically found for adsorbent materials that are carbon and MOF based materials, we show that in order to meet the Department of Energy targets of 180 V/V (equivalent STP) loading at 3.5 MPa and 298 K at the onboard packed bed level, the volumetric capacity of the pelletized sample should be at least 245 V/V and the corresponding gravimetric loading varies from 0.175 to 0.38 kg/kg for pellet densities ranging from 461.5 to 1,000 . With recent revision of the DOE target to 263 V/V at the onboard packed bed level, the volumetric loadings for the pelletized sample should be about 373 V/V.

Capturability Analysis of a 3-D Retro-PN Guidance Law for Higher Speed Nonmaneuvering Targets

This brief presents the capturability analysis of a 3-D Retro-proportional navigation (Retro-PN) guidance law, which uses a negative navigation constant (as against the usual positive one), for intercepting targets having higher speeds than interceptors. This modification makes it possible to achieve collision conditions that were inaccessible to the standard PN law. A modified polar coordinate system, that makes the model more compact, is used in this brief for capturability analysis. In addition to the ratio of the target to interceptor speeds, the directional cosines of the interceptor, and target velocity vectors play a crucial role in the capturability. The existence of nontrivial capture zone of the Retro-PN guidance law and necessary and sufficient conditions, for capturing the target in finite time, are presented. A sufficient condition on the navigation constant is derived to ensure finiteness of the line-of-sight turn rate. The results are more extensive than those available for 2-D engagements, which can be obtained as special cases of this brief. Simulation results are given to support the analytical results.

A novel Monoclonal Antibody against Notch1 Targets Leukemia-associated Mutant Notch1 and Depletes Therapy Resistant Cancer Stem Cells in Solid Tumors

Higher Notch signaling is known to be associated with hematological and solid cancers. We developed a potential immunotherapeutic monoclonal antibody (MAb) specific for the Negative Regulatory Region of Notch1 (NRR). The MAb604.107 exhibited higher affinity for the ``Gain-offunction'' mutants of Notch1 NRR associated with T Acute lymphoblastic Leukemia (T-ALL). Modeling of the mutant NRR with 12 amino-acid insertion demonstrated ``opening'' resulting in exposure of the S2-cleavage site leading to activated Notch1 signaling. The MAb, at low concentrations (1-2 mu g/ml), inhibited elevated ligand-independent Notch1 signaling of NRR mutants, augmented effect of Thapsigargin, an inhibitor of mutant Notch1, but had no effect on the wild-type Notch1. The antibody decreased proliferation of the primary T-ALL cells and depleted leukemia initiating CD34/CD44 high population. At relatively high concentrations, (10-20 mu g/ml), the MAb affected Notch1 signaling in the breast and colon cancer cell lines. The Notch-high cells sorted from solid-tumor cell lines exhibited characteristics of cancer stem cells, which were inhibited by the MAb. The antibody also increased the sensitivity to Doxorubucinirubicin. Further, the MAb impeded the growth of xenografts from breast and colon cancer cells potentiated regression of the tumors along with Doxorubucin. Thus, this antibody is potential immunotherapeutic tool for different cancers.

BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery

Hermansky-Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes. In BLOC-2-deficient melanocytes, the melanosomal protein TYRP1 was largely depleted from pigment granules and underwent accelerated recycling from endosomes to the plasma membrane and to the Golgi. By live-cell imaging, recycling endosomal tubules of wild-type melanocytes made frequent and prolonged contacts with maturing melanosomes; in contrast, tubules from BLOC-2-deficient cells were shorter in length and made fewer, more transient contacts with melanosomes. These results support a model in which BLOC-2 functions to direct recycling endosomal tubular transport intermediates to maturing melanosomes and thereby promote cargo delivery and optimal pigmentation.

Identification of microRNAs and their targets in Finger millet by high throughput sequencing

MicroRNAs are short non-coding RNAs which play an important role in regulating gene expression by mRNA cleavage or by translational repression. The majority of identified miRNAs were evolutionarily conserved; however, others expressed in a species-specific manner. Finger millet is an important cereal crop; nonetheless, no practical information is available on microRNAs to date. In this study, we have identified 95 conserved microRNAs belonging to 39 families and 3 novel microRNAs by high throughput sequencing. For the identified conserved and novel miRNAs a total of 507 targets were predicted. 11 miRNAs were validated and tissue specificity was determined by stem loop RT-qPCR, Northern blot. GO analyses revealed targets of miRNA were involved in wide range of regulatory functions. This study implies large number of known and novel miRNAs found in Finger millet which may play important role in growth and development. (C) 2015 Elsevier B.V. All rights reserved.

Recognizing drug targets using evolutionary information: implications for repurposing FDA-approved drugs against Mycobacterium tuberculosis H37Rv

Drug repurposing to explore target space has been gaining pace over the past decade with the upsurge in the use of systematic approaches for computational drug discovery. Such a cost and time-saving approach gains immense importance for pathogens of special interest, such as Mycobacterium tuberculosis H37Rv. We report a comprehensive approach to repurpose drugs, based on the exploration of evolutionary relationships inferred from the comparative sequence and structural analyses between targets of FDA-approved drugs and the proteins of M. tuberculosis. This approach has facilitated the identification of several polypharmacological drugs that could potentially target unexploited M. tuberculosis proteins. A total of 130 FDA-approved drugs, originally intended against other diseases, could be repurposed against 78 potential targets in M. tuberculosis. Additionally, we have also made an attempt to augment the chemical space by recognizing compounds structurally similar to FDA-approved drugs. For three of the attractive cases we have investigated the probable binding modes of the drugs in their corresponding M. tuberculosis targets by means of structural modelling. Such prospective targets and small molecules could be prioritized for experimental endeavours, and could significantly influence drug-discovery and drug-development programmes for tuberculosis.

Composite Guidance for Impact Angle Control Against Higher Speed Targets

In the literature, the impact angle control problem has been addressed mostly against lower speed or stationary targets. However, in the current defense scenario, targets of much higher speeds than interceptors are a reality. Moreover, approaching a higher speed target from a specified angle is important for effective seeker acquisition and enhanced warhead effectiveness. This paper proposes a composite proportional navigation guidance law using a combination of the standard proportional navigation and the recently proposed retroproportional navigation guidance laws for intercepting higher speed nonmaneuvering targets at specified impact angles in three-dimensional engagements. An analysis of the set of achievable impact angles by the composite proportional navigation guidance law is presented. It is shown that there exists an impulse bias that, when added to the composite proportional navigation guidance command, expands this set further by reversing the direction of the line-of-sight angular rotation vector. A bound on the magnitude of the bias is also derived. Finally, an implementation of this impulse bias, in the form of a series of pulses, is proposed and analyzed. Simulation results are also presented to support the analysis.