Synthesis and SAR of centrally active mGlu(5) positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold

This Letter describes the hit-to-lead progression and SAR of a series of biphenyl acetylene compounds derived from an HTS screening campaign targeting the mGlu(5) receptor. 'Molecular switches' were identified that modulated modes of pharmacology, and several compounds within this series were shown to be efficacious in reversal of amphetamine induced hyperlocomotion in rats after ip dosing, a preclinical model that shows similar positive effects with known antipsychotic agents. Published by Elsevier Ltd.

Analysis of information leakage from encrypted Skype conversations

Voice over IP (VoIP) has experienced a tremendous growth over the last few years and is now widely used among the population and for business purposes. The security of such VoIP systems is often assumed, creating a false sense of privacy. This paper investigates in detail the leakage of information from Skype, a widely used and protected VoIP application. Experiments have shown that isolated phonemes can be classified and given sentences identified. By using the dynamic time warping (DTW) algorithm, frequently used in speech processing, an accuracy of 60% can be reached. The results can be further improved by choosing specific training data and reach an accuracy of 83% under specific conditions. The initial results being speaker dependent, an approach involving the Kalman filter is proposed to extract the kernel of all training signals.

Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells.

Background Human respiratory syncytial virus (RSV) causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs). Methods To address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers. Results RSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates. Conclusions The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.

Potentially inappropriate prescribing in an Irish elderly population in primary care.

AIMS Screening tools have been formulated to identify potentially inappropriate prescribing (IP) in older people. Beers’ criteria are the most widely used but have disadvantages when used in Europe. New
IP screening tools called Screening Tool of Older Person’s Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) have been developed to identify potential IP and potential prescribing omissions (PPOs). The aim was to measure the prevalence rates of potential IP and PPOs in primary care using Beers’ criteria, STOPP and START.

METHODS
Case records of 1329 patients 65 years old from three general practices in one region of southern Ireland were studied. The mean age SD of the patients was 74.9 6.4 years, 60.9% were female. Patients’current diagnoses and prescription medicines were reviewed and the Beers’ criteria, STOPP and START tools applied.

RESULTS
The total number of medicines prescribed was 6684; median number of medicines per patient was ?ve (range 1–19). Overall, Beers’ criteria identi?ed 286 potentially inappropriate prescriptions in 18.3% (243) of patients, whilst the corresponding IP rate identi?ed by STOPP was 21.4% (284), in respect of 346 potentially inappropriate prescriptions. A total of 333 PPOs were identi?ed in 22.7% (302) of patients using the START tool.

CONCLUSION
Potentially inappropriate drug prescribing and errors of drug omission are highly prevalent among older people living in the community. Prevention strategies should involve primary care doctors and community pharmacists.

Image processing chip for small object detection

A new, front-end image processing chip is presented for real-time small object detection. It has been implemented using a 0.6 µ, 3.3 V CMOS technology and operates on 10-bit input data at 54 megasamples per second. It occupies an area of 12.9 mm×13.6 mm (including pads), dissipates 1.5 W, has 92 I/O pins and is to be housed in a 160-pin ceramic quarter flat-pack. It performs both one- and two-dimensional FIR filtering and a multilayer perceptron (MLP) neural network function using a reconfigurable array of 21 multiplication-accumulation cells which corresponds to a window size of 7×3. The chip can cope with images of 2047 pixels per line and can be cascaded to cope with larger window sizes. The chip performs two billion fixed point multiplications and additions per second.

Discovery of Main-Belt Comet P/2006 VW139 by Pan-STARRS 1

The main-belt asteroid (300163) 2006 VW139 (later designated P/2006 VW139) was discovered to exhibit comet-like activity by the Pan-STARRS1 (PS1) survey telescope using automated point-spread-function analyses performed by PS1's Moving Object Processing System. Deep follow-up observations show both a short (~10'') antisolar dust tail and a longer (~60'') dust trail aligned with the object's orbit plane, similar to the morphology observed for another main-belt comet (MBC), P/2010 R2 (La Sagra), and other well-established comets, implying the action of a long-lived, sublimation-driven emission event. Photometry showing the brightness of the near-nucleus coma remaining constant over ~30 days provides further evidence for this object's cometary nature, suggesting it is in fact an MBC, and not a disrupted asteroid. A spectroscopic search for CN emission was unsuccessful, though we find an upper limit CN production rate of Q CN 100 Myr, while a search for a potential asteroid family around the object reveals a cluster of 24 asteroids within a cutoff distance of 68 m s-1. At 70 m s-1, this cluster merges with the Themis family, suggesting that it could be similar to the Beagle family to which another MBC, 133P/Elst-Pizarro, belongs.

Effect of coinfection with genogroup 1 porcine torque teno virus on porcine circovirus type 2-associated postweaning multisystemic wasting syndrome in gnotobiotic pigs

Objective—To determine whether genogroup 1 porcine torque teno virus (g1-TTV) can potentiate clinical disease associated with porcine circovirus type 2 (PCV2).

Sample population—33 gnotobiotic baby pigs.

Procedures—Pigs were allocated into 7 groups: group A, 5 uninoculated control pigs from 3 litters; group B, 4 pigs oronasally inoculated with PCV2 alone; group C, 4 pigs inoculated IP with first-passage g1-TTV alone; group D, 4 pigs inoculated IP with fourth-passage g1-TTV alone; group E, 6 pigs inoculated IP with first-passage g1-TTV and then oronasally inoculated with PCV2 7 days later; group F, 6 pigs inoculated IP with fourth-passage g1-TTV and then inoculated oronasally with PCV2 7 days later; and group G, 4 pigs inoculated oro-nasally with PCV2 and then inoculated IP with fourth-passage g1-TTV 7 days later.

Results—6 of 12 pigs inoculated with g1-TTV prior to PCV2 developed acute onset of postweaning multisystemic wasting syndrome (PMWS). None of the pigs inoculated with g1-TTV alone or PCV2 alone or that were challenge exposed to g1-TTV after establishment of infection with PCV2 developed clinical illness. Uninoculated control pigs remained healthy.

Conclusions and Clinical Relevance—These data implicated g1-TTV as another viral infection that facilitates PCV2-induced PMWS. This raises the possibility that torque teno viruses in swine may contribute to disease expression currently associated with only a single infectious agent.

Relationship between electrical resistivity and basic geotechnical parameters for marine clays

Recently, considerable efforts have been made in the attempt to map quick clay areas using electrical resistivity measurements. However there is a lack of understanding regarding which soil parameters control the measured resistivity values. To address this issue, inverted resistivity values from 15 marine clay sites in Norway have been compared with basic geotechnical index properties. It was found that the resistivity value is strongly controlled by the salt content of the pore fluid. Resistivity decreases rapidly with increasing salt content. There is also a relatively clear trend of decreasing resistivity with increasing clay content and plasticity index. Resistivity values become very low (˜5 O·m) for high clay content (>50%), medium- to high-plasticity (Ip ˜ 20%) materials with salt content values greater than about 8 g/L (or corresponding remoulded shear strength values greater than 4 kPa). For the range of values studied, there is poor correlation between resistivity and bulk density and between resistivity and water content. The data studied suggest that the range of resistivity values corresponding to quick clay is 10 to 100 O·m, which is consistent with other published limits. A comparison is made between two-dimensional electrical resistivity tomography (ERT) and resistivity cone penetration test (RCPTU) data for two of the sites and the two sets of data show similar trends and values irrespective of scale effect.

From bit level systolic arrays to HDTV processor chips

The initial part of this paper reviews the early challenges (c 1980) in achieving real-time silicon implementations of DSP computations. In particular, it discusses research on application specific architectures, including bit level systolic circuits that led to important advances in achieving the DSP performance levels then required. These were many orders of magnitude greater than those achievable using programmable (including early DSP) processors, and were demonstrated through the design of commercial digital correlator and digital filter chips. As is discussed, an important challenge was the application of these concepts to recursive computations as occur, for example, in Infinite Impulse Response (IIR) filters. An important breakthrough was to show how fine grained pipelining can be used if arithmetic is performed most significant bit (msb) first. This can be achieved using redundant number systems, including carry-save arithmetic. This research and its practical benefits were again demonstrated through a number of novel IIR filter chip designs which at the time, exhibited performance much greater than previous solutions. The architectural insights gained coupled with the regular nature of many DSP and video processing computations also provided the foundation for new methods for the rapid design and synthesis of complex DSP System-on-Chip (SoC), Intellectual Property (IP) cores. This included the creation of a wide portfolio of commercial SoC video compression cores (MPEG2, MPEG4, H.264) for very high performance applications ranging from cell phones to High Definition TV (HDTV). The work provided the foundation for systematic methodologies, tools and design flows including high-level design optimizations based on "algorithmic engineering" and also led to the creation of the Abhainn tool environment for the design of complex heterogeneous DSP platforms comprising processors and multiple FPGAs. The paper concludes with a discussion of the problems faced by designers in developing complex DSP systems using current SoC technology. © 2007 Springer Science+Business Media, LLC.

JPEG encoder system-on-a-chip demonstrator

The design of a System-on-a-Chip (SoC) demonstrator for a baseline JPEG encoder core is presented. This combines a highly optimized Discrete Cosine Transform (DCT) and quantization unit with an entropy coder which has been realized using off-the-shelf synthesizable IP cores (Run-length coder, Huffman coder and data packer). When synthesized in a 0.35 µm CMOS process, the core can operate at speeds up to 100 MHz and contains 50 k gates plus 11.5 kbits of RAM. This is approximately 20% less than similar JPEG encoder designs reported in literature. When targeted at FPGA the core can operate up to 30 MHz and is capable of compressing 9-bit full-frame color input data at NTSC or PAL rates.

High-performance FPGA implementation of DES using a novel method for implementing the key schedule

A generic, parameterisable key scheduling core is presented, which can be utilised in pipelinable private-key encryption algorithms. The data encryption standard (DES) algorithm, which lends itself readily to pipelining, is utilised to exemplify this novel key scheduling method and the broader applicability of the method to other encryption algorithms is illustrated. The DES design is implemented on Xilinx Virtex FPGA technology. Utilising the novel method, a 16-stage pipelined DES design is achieved, which can run at an encryption rate of 3.87 Gbit/s. This result is among the fastest hardware implementations and is a factor 28 times faster than software implementations.

Rapid design of a single chip adaptive beamformer

This paper presents the design of a single chip adaptive beamformer which contains 5 million transistors and can perform 50 GigaFlops. The core processor of the adaptive beamformer is a QR-array processor implemented on a fully efficient linear systolic architecture. The paper highlights a number of rapid design techniques that have been used to realize the design. These include an architecture synthesis tool for quickly developing the circuit architecture and the utilization of a library of parameterizable silicon intellectual property (IP) cores, to rapidly develop the circuit layouts.

Programmable high-performance IIR filter chip

The paper presents a state-of-the-art commercial demonstrator chip for infinite impulse response (IIR) filtering. The programmable IIR filter chip contains eight multiplier/accumulators that can be configured in one of five different modes to implement up to a 16th-order IIR filter. The multiply-accumulate block is based on a highly regular systolic array architecture and uses a redundant number system to overcome problems of pipelining in the feedback loop. The chip has been designed using the GEC Plessey Semiconductors CLA 78000 series gate array, operates on 16-bit two's complement data and has a clock speed of 30 MHz. Issues such as overflow detection and design for testability have also been addressed and are described.