Supramolecular Assembly of Aminoethylene‐Lipopeptide PMO Conjugates into RNA Splice‐Switching Nanomicelles

Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile.     

Effect of waste serpentine on the properties of basic insulating refractories

Basic insulating refractories were fabricated by the pressing route using dead-burned magnesia, pure calcined alumina, expanded perlite, and calcined waste serpentine as starting raw materials in four compositions from F1 to F4. Periclase and forsterite were major phases in F1 and F2 compositions, while spinel was also detected in the XRD patterns of F3 and F4 samples. Quantitative phase analysis showed that F4 sample sintered at 1450?°C has the highest forsterite content among all other samples. On the other hand, it has lower thermal conductivity compared to F1 to F3, and even lower than aluminosilicate IFBs with the same bulk density. It is concluded that forsterite is a highly insulating material, compared to periclase, corundum, periclase-spinel, aluminosilicates, such as mullite, etc.     

IMPACCT: Methodology and Tools for Power-Aware Embedded Systems

Power-aware systems are those that must exploit a widerange of power/performance trade-offs in order to adapt to the power availabilityand application requirements. They require the integration of many novel powermanagement techniques, ranging from voltage scaling to subsystem shutdown.However, those techniques do not always compose synergistically with eachother; in fact, they can combine subtractively and often yield counterintuitive,and sometimes incorrect, results in the context of a complete system. Thiscan become a serious problem as more of these power aware systems are beingdeployed in mission critical applications.To address the problem of technique integration for power-aware embedded systems, we propose a new design tool framework called IMPACCT and the associated design methodology. The system modeling methodology includes application model for capturing timing/powerconstraints and mode dependencies at the system level. The tool performs power-awarescheduling and mode selection to ensure that all timing/power constraintsare satisfied and that all overhead is taken into account. IMPACCT then synthesizesthe implementation targeting a symmetric multiprocessor platform. Experimentalresults show that the increased dynamic range of power/performance settingsenabled a Mars rover to achieve significant acceleration while using lessenergy. More importantly, our tool correctly combines the state-of-the-arttechniques at the system level, thereby saving even experienced designersfrom many pitfalls of system-level power management.     

Energy-efficient video streaming over Bluetooth using rateless coding

Energy-efficient error control for IEEE 802.15.1 (Bluetooth) video communication is proposed. The scheme is based on block-oriented incremental redundancy provided by rateless coding and receiver feedback. Results are presented for time-sensitive video streaming applications under a Markovian channel model. When the proposed algorithm is compared to variations of Bluetooth forward error control, there are improvements of around 3 dB in received video quality and of over 10% in energy efficiency.     

A 2.5-Gb/s 15-mW clock recovery circuit

This paper describes the design of a 2.5-Gb/s 15-mW clock recovery circuit based on the quadricorrelator architecture. Employing both phase and frequency detection, the circuit combines high-speed operations such as differentiation, full-wave rectification, and mixing in one stage to lower the power dissipation. In addition, a two-stage voltage-controlled oscillator is utilized that incorporates both phase shift elements to provide a wide tuning range and isolation techniques to suppress the feedthrough due to input data transitions. Fabricated in a 20-GHz 1-μm BiCMOS technology, the circuit exhibits an rms jitter of 9.5 ps and a capture range of 300 MHz     

Statistical analysis of fiber-optic CDMA communication systems. I. Device modeling

In this paper, we present a new methodology for analysis of all-optical fiber-optic code-division multiple-access (FO-CDMA) networks. In this analysis, we propose statistical models, based on photon-counting techniques, for some basic elements of the network, such as splitters, combiners, star couplers, and FO-CDMA passive encoders/decoders. By following the statistical variation of the photon-count of the string of pulses that constitutes the address sequence in an FO-CDMA network, we will be able to reveal the quantum-limited optical signal-to-noise ratio (OSNR) required at the transmitter output to meet the performance limits. Moreover, considering receiver thermal noise and source extinction ratio, we explore the role of using an optical preamplifier before the detector and the dependence of the performance on the transmitted power and the weight of the employed optical orthogonal codes (OOCs).     

The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after i.v. administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P < 0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P < 0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.     

Real-time processing and compression of DNA microarray images.

In this paper, we present a pipeline architecture specifically designed to process and compress DNA microarray images. Many of the pixilated image generation methods produce one row of the image at a time. This property is fully exploited by the proposed pipeline that takes in one row of the produced image at each clock pulse and performs the necessary image processing steps on it. This will remove the present need for sluggish software routines that are considered a major bottleneck in the microarray technology. Moreover, two different structures are proposed for compressing DNA microarray images. The proposed architecture is proved to be highly modular, scalable, and suited for a standard cell VLSI implementation.     

A 6 GHz 68 mW BiCMOS phase-locked loop

The design of a 6 GHz fully monolithic phase-locked loop fabricated in a 1 μm, 20 GHz BiCMOS technology is described. The circuit incorporates a voltage-controlled oscillator that senses and combines the transitions in a ring oscillator to achieve a period equal to two ECL gate delays. A mixer topology is also used that exhibits full symmetry with respect to its inputs and operates with supply voltages as low as 1.5 V. Dissipating 60 mW from a 2 V supply, the circuit has a tracking range of 300 MHz, an rms jitter of 3.1 ps, and phase noise of -75 dBc/Hz at 1 kHz offset     

Influence of thermal boundary conditions on natural convection in a square enclosure partially heated from below

Natural convection in air-filled 2D square enclosure heated with a constant source from below and cooled from above is studied numerically for a variety of thermal boundary conditions at the top and sidewalls. Simulations are performed for two kinds of lengths of the heated source, i.e., a small and a large source corresponding to 20% and 80% of the total length of the bottom wall, respectively. The Rayleigh number varied from 10³ to 10⁷. Results are presented in the form of streamline and isotherm plots as well as the variation of the Nusselt number and maximum temperature at the heat source surface. Comparisons among the different thermal configurations considered are reported.