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.     

Non-starch polysaccharides of canola meal: Quantification,digestibility in poultry and potential benefit of dietary enzyme supplementation

The non-starch polysaccharide (NSP) content as determined by gas chromatography (component neutral sugars) and colorimetry (uronic acids) was shown to be 16–22% in ten different samples of defatted canola (low glucosinolate rapeseed) seed. The non-cellulosic components of NSP accounted for 13–16% of the meal and on average consisted of arabinose (33%), xylose (13%), galactose (13%), glucose (5%), mannose (3%), rhamnose (2%), fucose (2%) and uronic acids (30%). Yellow-seeded and brown-seeded samples of canola contained similar contents of total dietary fibre although the composition of the fibre components tended to differ with the former showing a low content of lignin and associated polyphenols and a high content of NSP as compared with the latter type. NDF values tended to be lower for yellow-seeded than for brown-seeded canola due to the relatively high content of NSP in neutral detergent solubles of yellow-seeded canola. An initial balance study with laying hens showed low (<3%) digestibility of the polysaccharide components, and further studies were conducted with a commercial enzyme preparation (SP249, Novo Laboratories Ltd, Lachine, Quebec) to enhance the in-vivo hydrolysis of the NSP fraction of the meal. Laying hens were fed a semipurified diet containing 40% commercial canola meal with and without enzyme (1%). NSP digestibility was increased to 37% by the enzyme supplementation.     

Call admission control schemes under generalized processor sharing scheduling

Provision of Quality‐of‐Service (QoS) guarantees is an important and challenging issue in the design of integrated‐services packet networks. Call admission control is an integral part of the challenge and is closely related to other aspects of networks such as service models, scheduling disciplines, traffic characterization and QoS specification. In this paper we provide a theoretical framework within which call admission control schemes with multiple statistical QoS guarantees can be constructed for the Generalized Processor Sharing (GPS) scheduling discipline. Using this framework, we present several admission control schemes for both session‐based and class‐based service models. The theoretical framework is based on recent results in the statistical analysis of the GPS scheduling discipline and the theory of effective bandwidths. Both optimal schemes and suboptimal schemes requiring less computational effort are studied under these service models. The QoS metric considered is loss probability. This revised version was published online in June 2006 with corrections to the Cover Date.     

Small Solutions to Polynomial Equations, and Low Exponent RSA Vulnerabilities

We show how to find sufficiently small integer solutions to a polynomial in a single variable modulo N, and to a polynomial in two variables over the integers. The methods sometimes extend to more variables. As applications: RSA encryption with exponent 3 is vulnerable if the opponent knows two-thirds of the message, or if two messages agree over eight-ninths of their length; and we can find the factors of N=PQ if we are given the high order bits of P. Received 21 December 1995 and revised 11 August 1996     

Automatic quantification of changes in bone in serial MR images of joints

Recent innovations in drug therapies have made it highly desirable to obtain sensitive biomarkers of disease progression that can be used to quantify the performance of candidate disease modifying drugs. In order to measure potential image-based biomarkers of disease progression in an experimental model of rheumatoid arthritis (RA), we present two different methods to automatically quantify changes in a bone in in-vivo serial magnetic resonance (MR) images from the model. Both methods are based on rigid and nonrigid image registration to perform the analysis. The first method uses segmentation propagation to delineate a bone from the serial MR images giving a global measure of temporal changes in bone volume. The second method uses rigid body registration to determine intensity change within a bone, and then maps these into a reference coordinate system using nonrigid registration. This gives a local measure of temporal changes in bone lesion volume. We detected significant temporal changes in local bone lesion volume in five out of eight identified candidate bone lesion regions, and significant difference in local bone lesion volume between male and female subjects in three out of eight candidate bone lesion regions. But the global bone volume was found to be fluctuating over time. Finally, we compare our findings with histology of the subjects and the manual segmentation of bone lesions.     

A 2-GHz clocked AlGaAs/GaAs HBT byte-slice datapath chip

A byte-slice datapath for exploring multi-chip RISC processor development in AlGaAs-GaAs heterojunction bipolar transistor (HBT) technology has been designed, fabricated and tested. The circuits are implemented using differential current-mode logic (CML) and emitter-coupled logic (ECL) with signal swings of 250 mV. Each datapath chip contains a single slice, including an 8-bit by 32-word single-port register file with a 230-ps read access time, and an 8-bit carry-select adder with a 140-ps select path and a 380-ps ripple-carry path. Each unpackaged die was tested using an at-speed boundary scan test scheme. The register file and adder carry chain are also implemented in a special test chip for accurate performance characterization of these critical circuits     

智能型激光控制器提高灵活性并节省空间

激光二极管是宽带调幅光纤发射系统的核心器件。光纤系统依赖于激光的稳定性,但未受调节控制的激光二极管特性却常因制造误差、温度和使用日久所造成的参数改变而变得不稳定。因此,光纤通信系统需要专用电路来控制重要的激光二极管参数,以确保它们稳定操作。虽然激光控制电路都     

Definition of the Geometric Area of a Microelectrode Tip by Plasma Etching of Parylene

The geometric area of the tip of an intracortical stimulation electrode can be defined by combining photoresist masking with oxygen plasma etching of Parylene.1 The method was tested with both capacitor and iridium oxide electrodes and caused no significant degradation of the electrical properties of the electrode.     

Avalanche buildup time of InP/InGaAsP/InGaAs avalanche photodiodes with separate absorption, grading, and multiplication regions

The avalanche buildup time of an avalanche photodiode can be determined from the frequency response of the noise power as a function of the dc multiplication M0. In this paper we report on the first measurements of the avalanche buildup time of InP/InGaAsP/ InGaAs avalanche photodiodes with separate absorption, grading, and multiplication regions (SAGM-APD's). Measurements on several different device structures reveal that the avalanche buildup time (gain-bandwidth product) decreases (increases) with increasing carrier concentration in the multiplication region. The shortest buildup time that we have observed wasM_{0} times 4.2ps which corresponds to a gain-bandwidth Product of 38 GHz.     

Measurement and prediction of digital radio performance on a long overwater path

The simultaneous field trial performance of 34 Mbit/s 4PSK, 2 × 34 Mbit/s 8PSK and 4 × 34 Mbit/s 16QAM digital radio systems over a 158 km overwater path in Australia is reported, and the measured outage performance is then used to derive propagation data, which in turn is used to predict performance using quadruple diversity. In addition, a generalised outage prediction technique is derived for n diversity.