Improved Tricyclic Inhibitors of Trypanothione Reductase by Screening and Chemical Synthesis

Trypanothione reductase (TryR) is a key validated enzyme in the trypanothione‐based redox metabolism of pathogenic trypanosomes and leishmania parasites. This system is absent in humans, being replaced with glutathione and glutathione reductase, and as such offers a target for selective inhibition. As part of a program to discover antiparasitic drugs, the LOPAC1280 library of 1266 compounds was screened against TryR and the top hits evaluated against glutathione reductase and T. brucei parasites. The top hits included a number of known tricyclic neuroleptic drugs along with other new scaffolds for TryR. Three novel druglike hits were identified and SAR studies on one of these using information from the tricyclic neuroleptic agents led to the discovery of a competitive inhibitor (K_i=330 nM ) with an improved potency against T. brucei (EC₅₀=775 nM ).     

Fabrication of porous polymer monoliths in polymeric microfluidic chips as an electrospray emitter for direct coupling to mass spectrometry

Coupling of polymeric microfluidic devices to mass spectrometry is reported using porous polymer monoliths (PPM) as nanoelectrospray emitters. Lauryl acrylate-co-ethylene dimethacrylate porous polymer monolith was photopatterned for 5 mm at the end of the channel of microfluidic devices fabricated from three different polymeric substrate materials, including the following: poly(dimethylsiloxane) (PDMS), poly(methyl methacrylate) (PMMA), and cyclic olefin copolymer (COC). Spraying directly from the end of the chip removes any dead volume associated with inserted emitters or transfer lines, and the presence of multiple pathways in the PPM prevents the clogging of the channels, which is a common problem in conventional nanospray emitters. Spraying from a microfluidic channel having a PPM emitter produced a substantial increase in TIC stability and increased sensitivity by as much as 70x compared to spraying from an open end chip with no PPM. The performance of PPM emitter in COC, PMMA, and PDMS chips was compared in terms of stability and reproducibility of the electrospray. COC chips showed the highest reproducibility in terms of chip-to-chip performance, which can be attributed to the ease and reproducibility of the PPM formation due to the favorable optical and chemical properties of COC. We have further tested the performance of the COC chips by constant infusion of poly(propylene glycol) solution at organic content ranging from 10 to 90% methanol and at flow rates ranging from 50 to 1000 nL/min, showing optimum spraying conditions (RSD < 5%) at 50-70% organic content and at flow rates from 100 to 500 nL/min. The PPM sprayer was also used for protein preconcentration and desalting prior to mass spectrometric detection, and results were comparable with a chip spraying from an electrospray tip.     

Circular tunnel in a semi-infinite aquifer

The steady gravity flow that is generated by a circular tunnel disturbing the hydrostatic state of a semi-infinite, homogeneous and isotropic aquifer is solved exactly. Many aspects of the flow are found in closed analytical forms such as the water inflow, pressure, leakage and recharging infiltration, which give a complete view of the aquifer in the drained steady state. It is found that the maximum value of the recharging infiltration does not exceed the hydraulic conductivity allowing stating a criteria for recharge intervention to ensure the stability of the aquifer. In addition to the main results, two aspects of the water inflow are treated. These are the necessary modifications that are to be considered in the case of an inclined water table and in the case of a lined tunnel that develops a constant internal pressure. It is also found that under an inclined water table a tunnel may cease to drain on its complete circumferential edge and a limiting condition is stated. Furthermore, the Muskat–Goodman and other water inflow predictions are compared to the exact gravity water inflow.     

Induced Cardiomyocyte Proliferation: A Promising Approach to Cure Heart Failure

Unlike some lower vertebrates which can completely regenerate their heart, the human heart is a terminally differentiated organ. Cardiomyocytes lost during cardiac injury and heart failure cannot be replaced due to their limited proliferative capacity. Therefore, cardiac injury generally leads to progressive failure. Here, we summarize the latest progress in research on methods to induce cardiomyocyte cell cycle entry and heart repair through the alteration of cardiomyocyte plasticity, which is emerging as an effective strategy to compensate for the loss of functional cardiomyocytes and improve the impaired heart functions.     

Adaptive scheduling mechanism for IPTV over WiMAX IEEE 802.16j networks

A WiMAX technology is a very promising Broadband Wireless Access technology that is able to transmit different service types. This latter can have different constraints such as traffic rate, maximum latency, and tolerated jitter. The IEEE 802.16 Medium Access Control specifies five types of QoS classes: UGS, rtPS, ertPS, nrtPS, and BE. However, the IEEE 802.16 standard does not specify the scheduling algorithm to be used. Operators have the choice among many existing scheduling techniques. Also, they can propose their own scheduling algorithms. In this paper, we propose a scheduling strategy (Adaptive Weighted Round Robin, AWRR) for various Internet Protocol Television (IPTV) services traffic over 802.16j networks. Our scheme adapts dynamically the scheduler operation to according queue load and quality of service constraints. In particular, the proposed mechanism gives more priority to high definition television and standard definition television traffic by using two schedulers. The proposed scheduling algorithm has been simulated using the QualNet network simulator. The experimental results show that our scheduler schemes AWRR have a better performance than the traditional scheduling techniques for rtPS traffic, which allows ensuring QoS requirements for IPTV application. Copyright © 2012 John Wiley & Sons, Ltd.     

OMAC: A new access control architecture for overlay multicast communications

Multicast communications concern the transfer of data among multiple users. Multicast communications can be provided at the network layer—an example is IP multicast—or at the application layer, also called overlay multicast. An important issue in multicast communications is to control how different users—senders, receivers, and delivery nodes—access the transmitted data as well as the network resources. Many researchers have proposed solutions addressing access control in IP multicast. However, little attention has been paid to overlay multicast. In this paper, we investigate the access control issues in overlay multicast and present OMAC: a new solution to address these issues. OMAC provides access control for senders, receivers, and delivery nodes in overlay multicast. The proposed architecture, which is based on symmetric key cryptosystem, centralizes the authentication process in one server whereas it distributes the authorization process among the delivery nodes. Moreover, delivery nodes are utilized as a buffer zone between end systems and the authentication server, making it less exposed to malicious end systems. To evaluate our work, we have used simulation to compare the performance of OMAC against previous solutions. Results of the simulation show that OMAC outperforms previous multicast access control schemes. Copyright © 2010 John Wiley & Sons, Ltd.     

Target Multiplicity Performance Analysis of Radar CFAR Detection Techniques for Partially Correlated Chi-Square Targets

Most radar targets are complex objects and produce a wide variety of reflections. An important class of targets is represented by the so-called moderately fluctuating Rayleigh targets, which, when illuminated by a coherent pulse train, return a train of correlated pulses with a correlation coefficient in the range 0<ρ<1 (intermediate between SWII and SWI models). The detection of this type of fluctuating targets is therefore of great interest. On the other hand, the CFAR detection is one of the desirable features for radar receivers. Because of the simplicity of cell-averaging (CA detectors in their implementation, they are commonly used in modern radar systems to automatically adapt the detection threshold to the local background noise or clutter power in an attempt to maintain an approximately constant rate of false alarm. In this paper, we analyze the performance of these detectors for the case where the radar receiver postdetection integrates M square-law detected pulses and the signal fluctuation obeys chi-square statistics with two degrees of freedom. These detectors include the mean-level ML), the greatest-of (GO) and the smallest-of (SO) schemes. In these processors, the estimation of the noise power levels from the leading and the trailing reference windows is based on the CA technique. Exact formulas for the detection probabilities are derived, in the absence as well as in the presence of spurious targets. The primary and the secondary interfering targets are assumed to be fluctuating in accordance with the chi-square fluctuation model with two degrees of freedom. Swerling's well known fluctuation models I and II represent the cases where the signal is completely correlated and completely decorrelated, respectively, from pulse to pulse. Probability of detection curves are presented for the chi-square family of fluctuations, including the Swerling cases I and II. The ML detector has the best homogeneous performance, the SO processor has the best multiple-target performance, while the GO scheme does not offer any merits neither in the absence nor in the presence of outlying targets.     

Characterization of Short Intense Pulsed Electrothermal Plasma Capillaries for Use as Fusion and Launchers Heat Flux Sources

Electrothermal plasma sources operating in the confined capillary arc regime are characterized by the magnitude and shape of the discharge current. The desired plasma parameters at the source exit, especially the pressure and heat flux, are highly dependent on the arc due to the effect of the arc radiant energy that ablates the inner wall of the source. These sources have applications in fusion as drivers for pellet injectors and as high heat flux sources for fusion materials studies. The high-pressure high heat flux flow is also of application in mass accelerators and launch technology systems. The 1-D, time-dependent ETFLOW capillary code models the plasma generation and flow inside the capillary discharges and determines the plasma parameters. The input file to the code is the discharge current density providing the Joule heating in the energy equation. A circuit module has been developed and incorporated in the code to generate desired current shapes and magnitudes. The current pulse length was varied between 5 and 100 μs at constant amplitude of 50 kA, and then the pulse amplitude was varied between 10 and 200 kA at a constant pulse length of 20 μs. Increasing the pulse length while maintaining its amplitude increases the plasma density and the total ablated mass, which have accumulation behavior by increasing the pulse length, and subsequently increases the exit pressure from 60 to 410 MPa in the cases studied herein. The pressure increase allows the thermalization of the plasma particles through more collisions, which reduces the plasma temperature by about 0.2 eV. The bulk velocity follows the trend of the plasma temperature, but at shorter pulse lengths the total ablated mass is lower and enables the plasma to carry the particles with increasing velocity. Increasing the pulse amplitude up to 200 kA increases the density to about 18 kg/m³ and the bulk velocity, which varies between 6.1 and 10.7 km/s. A sharp increase in most plasma parameters occurs as a result of the increase in the pulse amplitude.