CiteULike: Author Hughes

Social Disclosure of Place: From Location Technology to Communication Practices

Ian Smith — 2006-11-08T02:23:15-00:00

Lecture Notes in Computer Science : Pervasive Computing (2005), pp. 134-151.

Place Lab: Device Positioning Using Radio Beacons in the Wild

Anthony Lamarca — 2007-02-14T19:45:49-00:00

Pervasive Computing (2005), pp. 116-133.

Location awareness is an important capability for mobile computing. Yet inexpensive, pervasive positioning—a requirement for wide-scale adoption of location-aware computing—has been elusive. We demonstrate a radio beacon-based approach to location, called Place Lab, that can overcome the lack of ubiquity and high-cost found in existing location sensing approaches. Using Place Lab, commodity laptops, PDAs and cell phones estimate their position by listening for the cell IDs of fixed radio beacons, such as wireless access points, and referencing the beacons’ positions in a cached database. We present experimental results showing that 802.11 and GSM beacons are sufficiently pervasive in the greater Seattle area to achieve 20-30 meter median accuracy with nearly 100% coverage measured by availability in people’s daily lives.

An analytical framework for evaluating peer-to-peer business models

Jerald Hughes — 2008-08-21T10:55:18-00:00

Electronic Commerce Research and Applications, Vol. 7, No. 1. ( 2008), pp. 105-118.

While existing research on peer-to-peer (P2P) file-sharing services has increased our understanding in many respects, it has not yet supplied a comprehensive theoretical framework that explains business failures of P2P file-sharing network service models. We develop such an analytical model and base it on seven specific market constraints - technical, economic, structural, legal, political, cognitive, and cultural - that are specifically relevant for P2P services. We show how our model can be used as a tool for strategic analysis of P2P business model performance using Napster as a particular case of study. We show also how P2P file-sharing networks have migrated through a series of system typologies by incorporating technological innovations in response to market constraints. Finally, we offer a new theoretical conceptualization that views P2P file-sharing networks as electronic markets.

Smooth meshes for sketch-based freeform modeling

Takeo Igarashi — 2008-08-21T09:21:31-00:00

(2006)

Mutations of the BRAF gene in human cancer

Helen Davies — 2007-05-02T15:04:29-00:00

Nature, Vol. 417, No. 6892. (27 June 2002), pp. 949-954.

An integer programming model for distal humerus fracture fixation planning.

JD Maratt — 2008-08-20T10:54:06-00:00

Computer aided surgery : official journal of the International Society for Computer Aided Surgery, Vol. 13, No. 3. (May 2008), pp. 139-147.

OBJECTIVE: To demonstrate the feasibility of an integer programming model to assist in pre-operative planning for open reduction and internal fixation of a distal humerus fracture. MATERIALS AND METHODS: We describe an integer programming model based on the objective of maximizing the reward for screws placed while satisfying the requirements for sound internal fixation. The model maximizes the number of bicortical screws placed while avoiding screw collision and favoring screws of greater length that cross multiple fracture planes. RESULTS: The model was tested on three types of total articular fractures of the distal humerus. Solutions were generated using 5, 9, 21 and 33 possible screw orientations per hole. Solutions generated using 33 possible screw orientations per hole and five screw lengths resulted in the most clinically relevant fixation plan and required the calculation of 1,191,975 pairs of screws that resulted in collision. At this level of complexity, the pre-processor took 104 seconds to generate the constraints for the solver, and a solution was generated in under one minute in all three cases. CONCLUSION: Despite the large size of this problem, it can be solved in a reasonable amount of time, making use of the model practical in pre-surgical planning.

Influence of Windfarms on Power System Dynamic and Transient Stability

Anaya-Lara — 2006-08-13T12:20:05-00:00

Wind Engineering, Vol. 30, No. 2. (March 2006), pp. 107-127.

Why is the choice of future climate scenarios for species distribution modelling important?

Linda Beaumont — 2008-08-18T16:52:30-00:00

Ecology Letters, Vol. 9999, No. 9999. (2008)

Species distribution models (SDMs) are common tools for assessing the potential impact of climate change on species ranges. Uncertainty in SDM output occurs due to differences among alternate models, species characteristics and scenarios of future climate. While considerable effort is being devoted to identifying and quantifying the first two sources of variation, a greater understanding of climate scenarios and how they affect SDM output is also needed. Climate models are complex tools: variability occurs among alternate simulations, and no single 'best' model exists. The selection of climate scenarios for impacts assessments should not be undertaken arbitrarily - strengths and weakness of different climate models should be considered. In this paper, we provide bioclimatic modellers with an overview of emissions scenarios and climate models, discuss uncertainty surrounding projections of future climate and suggest steps that can be taken to reduce and communicate climate scenario-related uncertainty in assessments of future species responses to climate change.

Image-detected breast cancer: state of the art diagnosis and treatment.

MJ Silverstein — 2008-08-18T15:50:38-00:00

Journal of the American College of Surgeons, Vol. 201, No. 4. (October 2005), pp. 586-597.

Understanding ERM proteins--the awesome power of genetics finally brought to bear.

SC Hughes — 2008-08-18T13:32:59-00:00

Current opinion in cell biology, Vol. 19, No. 1. (February 2007), pp. 51-56.

In epithelial cells, the Ezrin, Radixin and Moesin (ERM) proteins are involved in many cellular functions, including regulation of actin cytoskeleton, control of cell shape, adhesion and motility, and modulation of signaling pathways. However, discerning the specific cellular roles of ERMs has been complicated by redundancy between these proteins. Recent genetic studies in model organisms have identified unique roles for ERM proteins. These include the regulation of morphogenesis and maintenance of integrity of epithelial cells, stabilization of intercellular junctions, and regulation of the Rho small GTPase. These studies also suggest that ERMs have roles in actomyosin contractility and vesicular trafficking in the apical domain of epithelial cells. Thus, genetic analysis has enhanced our understanding of these widely expressed membrane-associated proteins.

Nell1-deficient mice have reduced expression of extracellular matrix proteins causing cranial and vertebral defects

Jayashree Desai — 2006-04-07T10:47:15-00:00

Human Molecular Genetics, Vol. 15, No. 8. (15 April 2006), pp. 1329-1341.

Small is beautiful: microRNAs and breast cancer-where are we now?

E Verghese — 2008-06-27T08:09:23-00:00

The Journal of pathology, Vol. 215, No. 3. (July 2008), pp. 214-221.

MicroRNAs are a recently discovered class of small regulatory RNAs that influence the stability and translational efficiency of target mRNAs. They have been implicated in an increasing number of biological processes, including neoplasia. Recent studies have shown an involvement for these regulatory molecules in breast cancer. For example, miRNA profiling studies have identified microRNAs that are deregulated in breast cancer. Furthermore, functional studies have uncovered their roles in breast cancer as both tumour suppressor genes (eg miR-335) and oncogenes (eg miR-21). miRNAs deregulated in breast cancer influence the translational regulation of well-established regulatory molecules, such as oestrogen receptor-alpha, which is regulated by miR-206, and novel cancer-related molecules whose functions are not yet fully understood.. Here we present an overview of our current understanding of miRNA in breast cancer. Copyright (c) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Effects of cocaine and alcohol, alone and in combination, on human learning and performance.

ST Higgins — 2008-08-15T21:12:39-00:00

Journal of the experimental analysis of behavior, Vol. 58, No. 1. (July 1992), pp. 87-105.

The acute effects of cocaine hydrochloride (4 to 96 mg/70 kg) and alcohol (0 to 1.0 g/kg), administered alone and in combination, were assessed in two experiments with human volunteers responding under a multiple schedule of repeated acquisition and performance of response chains. Subjects were intermittent users of cocaine and regular drinkers who were not cocaine or alcohol dependent. Alcohol was mixed with orange juice and ingested in six drinks within 30 min; cocaine was administered intranasally 45 min after completion of drinking. In each component of the multiple schedule, subjects completed response sequences using three keys of a numeric keypad. In the acquisition component, a new sequence was learned each session. In the performance component, the response sequence always remained the same. Results were consistent in both experiments, despite variations in the order in which the drugs were tested alone and in combination. Alcohol administered alone increased overall percentage of errors and decreased rates of responding in the acquisition component, whereas responding in the performance component generally was unaffected. Cocaine administered alone decreased rates of responding but did not affect accuracy of responding in the acquisition component, and enhanced accuracy of responding without affecting rates of responding in the performance component. The combined doses of cocaine and alcohol attenuated the effects observed with alcohol and cocaine alone. These results suggest that, under the conditions investigated in this study, (a) alcohol produces greater behavioral disruption than cocaine or cocaine-alcohol combinations, (b) cocaine and alcohol each attenuate effects of the other, and (c) such attenuation is most pronounced for cocaine attenuating the disruptive effects of alcohol.

Metalloproteinase expression in PMA-stimulated THP-1 cells. Effects of peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonists and 9-cis-retinoic acid.

JR Worley — 2008-08-15T13:53:05-00:00

The Journal of biological chemistry, Vol. 278, No. 51. (19 December 2003), pp. 51340-51346.

The PPAR gamma agonists, thiazolidinediones (TZDs), have anti-inflammatory properties as well as increasing insulin sensitivity. This has widened their therapeutic scope to treat inflammatory diseases such as atherosclerosis in addition to Type 2 Diabetes. TZDs are known to reduce monocyte/macrophage expression of Matrix metalloproteinase (MMP)-9, which is implicated in atherosclerotic plaque destabilization. This study aims to identify other metalloproteinase genes of the ADAM (A Disintegin And Metalloproteinase) and ADAMTS families that are regulated by PPAR gamma or RXR agonists, which are potentially important in type 2 diabetes and/or related atherosclerosis. The synthetic PPAR gamma agonist, GW7845, and the natural agonist 15d-PGJ2, suppressed PMA stimulated MMP-9 in human monocyte-like cells (THP-1) only in the presence of 9-cis-retinoic acid. Quantitative Real-Time PCR showed that this reduction was regulated at the mRNA level. Expression of ADAMs 8, 9, and 17 were increased, and ADAM15 was decreased by stimulation of THP-1 with PMA, although these ADAMs were not regulated by PPAR gamma or RXR agonists. PMA-induced ADAM28 expression was further enhanced by the addition of 9-cis-retinoic acid. ADAMTS4, implicated in rheumatoid arthritis, was expressed in THP-1 cells, and significantly increased after 24 h of PMA stimulation. ADAMTS4 expression was suppressed by both PPAR gamma and RXR agonists and was undetectable when the agonists were combined. Pretreatment of THP-1 cells with the PPAR gamma antagonist, GW9662, suggests that PPAR gamma plays subtly different roles in the regulation of MMP-9, ADAMTS4 and ADAM28 gene expression. These results indicate that PPAR gamma and RXR agonists have complex effects on monocyte metalloproteinase expression, which may have implications for therapeutic strategies.

The inhibition of polo kinase by matrimony maintains G2 arrest in the meiotic cell cycle.

Y Xiang — 2008-08-14T21:44:02-00:00

PLoS biology, Vol. 5, No. 12. (December 2007)

Many meiotic systems in female animals include a lengthy arrest in G2 that separates the end of pachytene from nuclear envelope breakdown (NEB). However, the mechanisms by which a meiotic cell can arrest for long periods of time (decades in human females) have remained a mystery. The Drosophila Matrimony (Mtrm) protein is expressed from the end of pachytene until the completion of meiosis I. Loss-of-function mtrm mutants result in precocious NEB. Coimmunoprecipitation experiments reveal that Mtrm physically interacts with Polo kinase (Polo) in vivo, and multidimensional protein identification technology mass spectrometry analysis reveals that Mtrm binds to Polo with an approximate stoichiometry of 1:1. Mutation of a Polo-Box Domain (PBD) binding site in Mtrm ablates the function of Mtrm and the physical interaction of Mtrm with Polo. The meiotic defects observed in mtrm/+ heterozygotes are fully suppressed by reducing the dose of polo+, demonstrating that Mtrm acts as an inhibitor of Polo. Mtrm acts as a negative regulator of Polo during the later stages of G2 arrest. Indeed, both the repression of Polo expression until stage 11 and the inactivation of newly synthesized Polo by Mtrm until stage 13 play critical roles in maintaining and properly terminating G2 arrest. Our data suggest a model in which the eventual activation of Cdc25 by an excess of Polo at stage 13 triggers NEB and entry into prometaphase.

Experiences with open overlays: a middleware approach to network heterogeneity

Paul Grace — 2008-08-14T15:10:22-00:00

(2008), pp. 123-136.

Parenting programme for parents of children at risk of developing conduct disorder: cost effectiveness analysis.

RT Edwards — 2008-08-14T04:52:49-00:00

BMJ (Clinical research ed.), Vol. 334, No. 7595. (31 March 2007)

OBJECTIVE: To investigate the cost effectiveness of a parenting programme. DESIGN: An incremental cost effectiveness analysis alongside a pragmatic randomised controlled trial of the effectiveness of a group parenting programme delivered through Sure Start in the community. SETTING: Sure Start areas in north and mid Wales. PARTICIPANTS: Parents of 116 children aged 36-59 months (87% of the clinical sample) at risk of developing conduct disorders defined by scoring over the clinical cut off on the Eyberg child behaviour inventory). Children were identified by health visitors and recruited by the research team. INTERVENTION: The Webster-Stratton Incredible Years basic parenting programme or a six month waiting list control. MAIN OUTCOME MEASURE: Incremental cost per unit of improvement on the intensity score of the Eyberg child behaviour inventory. RESULTS: The bootstrapped incremental cost effectiveness ratio point estimate was 73 pounds sterling (109 euros, $142) per one point improvement on the intensity score (95% confidence interval 42 pounds sterling to 140 pounds sterling ). It would cost 5486 (8190 euros, $10,666) to bring the child with the highest intensity score to below the clinical cut-off point and 1344 (2006 euros, $2618) to bring the average child in the intervention group within the non-clinical limits on the intensity score (below 127). For a ceiling ratio of 100 pounds sterling (149 euros, $194) per point increase in intensity score, there is an 83.9% chance of the intervention being cost effective. The mean cost per child attending the parenting group was 1934 pounds sterling (2887 euros, $3760) for eight children and 1289 pounds sterling (1924 euros, $2506) for 12 children, including initial costs and materials for training group leaders. When we categorised the sample into relatively mild, moderate, and severe behaviour groups based on intensity scores at baseline the intervention seemed more cost effective in those with the highest risk of developing conduct disorder. CONCLUSION: This parenting programme improves child behaviour as measured by the intensity score of the Eyberg child behaviour inventory at a relatively low cost and was cost effective compared with the waiting list control. This parenting programme involves modest costs and demonstrates strong clinical effect, suggesting it would represent good value for money for public spending.

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae

Nevan Krogan — 2006-03-23T02:32:52-00:00

Nature (22 March 2006)

Leave Regulation to the FDA

Owen Hughes — 2008-08-12T13:51:01-00:00

Science, Vol. 321, No. 5888. (25 July 2008), 490a.

10.1126/science.321.5888.490a

Beyond-brand effect of television food advertisements on food choice in children: the effects of weight status

Jason Halford — 2008-08-11T22:21:45-00:00

Public Health Nutrition, Vol. 11, No. 09. (2007), pp. 897-904.

<span class="AbstractTtl">Objective</span> To investigate the effect of television food advertising on children’s food intake, specifically whether childhood obesity is related to a greater susceptibility to food promotion.

Ocular tracking as a measure of auditory motion perception

Leanne Boucher — 2008-08-11T14:56:42-00:00

Journal of Physiology-Paris, Vol. 98, No. 1-3. ( 2004), pp. 235-248.

Motion is a potent sub-modality of vision. Motion cues alone can be used to segment images into figure and ground and break camouflage. Specific patterns of motion support vivid percepts of form, guide locomotion by specifying directional heading and the passage of objects, and in case of an impending collision, the time to impact. Visual motion also drives smooth pursuit eye movements (SPEMs) that serve to stabilize the retinal image of objects in motion. In contrast, the auditory system does not appear to be particularly sensitive to motion. We review the ambiguous status of auditory motion processing from the psychophysical and electrophysiological perspectives. We then report the results of two experiments that use ocular tracking performance as an objective measure of the perception of auditory motion in humans. We examine ocular tracking of auditory motion, visual motion, combined auditory + visual motion and imagined motion in both the frontal plane and in depth. The results demonstrate that ocular tracking of auditory motion is no better than ocular tracking of imagined motion. These results are consistent with the suggestion that, unlike the visual system, the human auditory system is not endowed with low-level motion sensitive elements. We hypothesize however, that auditory information may gain access to a recently described high-level motion processing system that is heavily dependent on [`]top-down' influences, including attention.

Southern Cosmology Survey I: Optical Cluster Detections and Predictions for the Southern Common-Area Millimeter-Wave Experiments

Felipe Menanteau — 2008-08-05T07:49:49-00:00

(1 Aug 2008)

We present first results from the Southern Cosmology Survey, a new multiwavelength survey of the southern sky coordinated with the Atacama Cosmology Telescope (ACT), a recently commissioned ground-based mm-band Cosmic Microwave Background experiment. This article presents a full analysis of archival optical multi-band imaging data covering an 8 square degree region near right ascension 23 hours and declination -55 degrees, obtained by the Blanco 4-m telescope and Mosaic-II camera in late 2005. We describe the pipeline we have developed to process this large data volume, obtain accurate photometric redshifts, and detect optical clusters. Our cluster finding process uses the combination of a matched spatial filter, photometric redshift probability distributions and richness estimation. We present photometric redshifts, richness estimates, luminosities, and masses for 8 new optically-selected clusters with mass greater than $3×10^14M_\sun$ at redshifts out to 0.7. We also present estimates for the expected Sunyaev-Zel'dovich effect (SZE) signal from these clusters as specific predictions for upcoming observations by ACT, the South Pole Telescope and Atacama Pathfinder Experiment.

Information hiding, anonymity and privacy: a modular approach

Dominic Hughes — 2008-08-11T12:11:16-00:00

J. Comput. Secur., Vol. 12, No. 1. (January 2004), pp. 3-36.

We propose a new specification framework for information hiding properties such as anonymity and privacy. The framework is based on the concept of a function view, which is a concise representation of the attacker's partial knowledge about a function. We describe system behavior as a set of functions, and formalize different information hiding properties in terms of views of these functions. We present an extensive case study, in which we use the function view framework to systematically classify and rigorously define a rich domain of identity-related properties, and to demonstrate that privacy and anonymity are independent. The key feature of our approach is its modularity. It yields precise, formal specifications of information hiding properties for any protocol formalism and any choice of the attacker model as long as the latter induce an observational equivalence relation on protocol instances. In particular, specifications based on function views are suitable for any cryptographic process calculus that defines some form of indistinguishability between processes. Our definitions of information hiding properties take into account any feature of the security model, including probabilities, random number generation, timing, etc., to the extent that it is accounted for by the formalism in which the system is specified.

Foodborne transmission of infectious intestinal disease in England and Wales, 1992-2003

C Hughes — 2008-08-10T09:55:08-00:00

Food Control, Vol. 18, No. 7. (July 2007), pp. 766-772.

This paper reports information on foodborne outbreaks of infectious intestinal disease (IID) in England and Wales during the period 1992-2003 collected as part of a major investigation into Breakdowns in Food Safety. Between 1992 and 2003, 7620 general outbreaks of IID were reported to the Communicable Disease Surveillance Centre and in 1729 (23%) the mode of transmission was described as foodborne. In total, 39,625 people were affected and 68 deaths reported. Salmonella spp. were implicated in over half of all foodborne outbreaks. During the surveillance period, the proportion of outbreaks attributed to Salmonella spp., Clostridium perfringens and Vero cytotoxin-producing Escherichia coli O157 decreased, whereas the proportion of outbreaks attributed to Campylobacters increased.

Statistical characteristics and multiplexing of MPEG streams

Marwan Krunz — 2008-08-09T14:20:55-00:00

(1995), pp. 455-462.

This paper presents a study of the statistical characteristics and multiplexing of Variable-Bit-Rate (VBR) MPEG-coded video streams. Our results are based on 23 minutes of video obtained from the entertainment movie, The Wizard of Oz. The experimental setup which was used to capture, digitize, and compress the video stream is described. Although the study is conducted at the frame level (as opposed to the slice level), it is observed that the inter-frame correlation structure for the frame-size sequence involves complicated forms of pseudo-periodicity that are mainly affected by the compression pattern of the sequence. A simple model for an MPEG traffic source is developed in which frames are generated according to the compression pattern of the original captured video stream. The number of cells per frame is fitted by a lognormal distribution. Simulations are used to study the performance of an ATM multiplexer for MPEG streams. 1

A traffic model for mpeg-coded VBR streams

Marwan Krunz — 2008-08-09T14:17:18-00:00

(1995), pp. 47-55.

Compression of digital video is the only viable means to transport real-time full-motion video over BISDN/ATM networks. Traffic streams generated by video compressors exhibit complicated patterns which vary from one compression scheme to another. In this paper we investigate the traffic characteristics of video streams which are compressed based on the MPEG standard. Our study is based on 23 minutes of video obtained from an entertainment movie. A particular significance of our data is that it contains all types of coded frames, namely: Intra-coded (I), Prediction (P), and Bidirectional (B) MPEG frames. We describe the statistical behavior of the VBR stream using histograms and autocorrelation functions. A procedure is developed to determine the instants of a scene change based on the changes in the size of successive I frames. It is found that the length of a scene can be modeled by a geometric distribution. A model for an MPEG traffic source is developed in which frames are generated according to the compression pattern of the captured video stream. For each frame type, the number of cells per frame is fitted by a lognormal distribution whose parameters are determined by the frame type. The appropriateness and limitations of the model are examined by studying the multiplexing performance of MPEG streams. Simulations of an ATM multiplexer are conducted, in which traffic sources are derived from the measured VBR trace as well as the proposed model. The queueing performance in both cases is found to be relatively close.

A Common Missense Variant in the Glucokinase Regulatory Protein Gene (GCKR) Is Associated with Increased Plasma Triglyceride and C-Reactive Protein but Lower Fasting Glucose Concentrations.

Marju Orho-Melander — 2008-08-07T09:14:05-00:00

Diabetes (4 August 2008)

OBJECTIVE Using the genome-wide-association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry, and to fine-map across the associated genomic interval. RESEARCH DESIGN AND METHODS We performed association studies in 12 independent cohorts comprising a total of >45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the United States, African Americans from the United States, Hispanics of Caribbean origin, and Chinese, Malays and Asian Indians from Singapore). We conducted genetic fine-mapping across the approximately 417 kilobase region of linkage disequilibrium spanning GCKR and 16 other genes on chromosome 2p23 by imputing untyped HapMap SNPs and genotyping 104 SNPs across the associated genomic interval.. RESULTS We provide comprehensive evidence that GCKR rs780094 is associated with opposite effects on fasting plasma triglyceride (p(meta)=3x10(-56)) and glucose (p(meta)=1x10(-13)) concentrations. In addition, we confirmed recent reports that the same SNP is associated with C-reative protein level (p=5x10(-5)). Both fine mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r(2)=0.93 with rs780094) as the strongest association signal in the region. CONCLUSIONS- These findings point to a molecular mechanism in humans by which higher triglycerides and C-reactive protein can be coupled with lower plasma glucose concentrations and position GCKR in central pathways regulating both hepatic triglyceride and glucose metabolism.

Incorporating Spatial Dependence and Atmospheric Data in a Model of Precipitation

James Hughes — 2008-08-06T23:47:15-00:00

Journal of Applied Meteorology, Vol. 33, No. 12. (1 December 1994), pp. 1503-1515.

Nonhomogeneous hidden Markov models (NHMM) provide a method of relating synoptic atmospheric measurements to precipitation occurrence at a network of rain gauge stations. In previous work it was assumed that, conditional on the current atmospheric pattern (termed a “weather state”), rain gauge stations in a network could be considered spatially independent. For a spatially dense network, this assumption is not tenable. In the present work, the NHMM is extended to include the case of spatial dependence by postulating an autologistic model for the conditional probability of rainfall given the weather state. Methods for fitting the parameters, assessing the goodness of fit of the model, and generating rainfall simulations are presented. The model is applied to a network of 24 stations in the Puget Sound region of western Washington State.

Effect of Lyophilization and Freeze-thawing on the Stability of siRNA-liposome Complexes

Preeti Yadava — 2008-07-21T11:43:30-00:00

AAPS PharmSciTech, Vol. 9, No. 2. (1 June 2008), pp. 335-341.

Abstract The purpose of this research was to describe the application of lyophilization in the delivery of siRNA using cationic lipids by addressing the long-term formulation/stability issues associated with cationic lipids and to understand the mechanism of lyoprotection. siRNA liposomes complexes were formed in different potential cyro/lyoprotectants and subjected to either lyophilization or freeze thaw cycles. siRNA, liposomes and/or lipoplexes were tested for activity, SYBR Green I binding, cellular uptake and particle size. The lipoplexes when lyophilized in the presence of sugars as lyoprotectants could be lyophilized and reconstituted without loss of transfection efficacy but in ionic solutions they lost 65–75% of their functionality. The mechanism of this loss of activity was further investigated. The lyophilization process did not alter siRNA’s intrinsic biological activity as was evident by the ability of lyophilized siRNA to retain functionality and SYBR green I binding ability. While the lipoplex size dramatically increased (∼50–70 times) after lyophilization in the absence of non-ionic lyoprotectants. This increase in size correlated to the decrease in cellular accumulation of siRNA and a decrease in activity. In conclusion, siRNAs can be applied in cationic lipid lyophilized formulations and these complexes represent a potential method of increasing the stability of pre-formed complex.

Gene duplication and the properties of biological networks.

AL Hughes — 2006-05-31T06:37:39-00:00

J Mol Evol, Vol. 61, No. 6. (December 2005), pp. 758-764.

Patterns of network connection of members of multigene families were examined for two biological networks: a genetic network from the yeast Saccharomyces cerevisiae and a protein-protein interaction network from Caenorhabditis elegans. In both networks, genes belonging to gene families represented by a single member in the genome ("singletons") were disproportionately represented among the nodes having large numbers of connections. Of 68 single-member yeast families with 25 or more network connections, 28 (44.4%) were located in duplicated genomic segments believed to have originated from an ancient polyploidization event; thus, each of these 28 loci was thus presumably duplicated along with the genomic segment to which it belongs, but one of the two duplicates has subsequently been deleted. Nodes connected to major "hubs" with a large number of connections, tended to be relatively sparsely interconnected among themselves. Furthermore, duplicated genes, even those arising from recent duplication, rarely shared many network connections, suggesting that network connections are remarkably labile over evolutionary time. These factors serve to explain well-known general properties of biological networks, including their scale-free and modular nature.

Alternative splicing of conserved exons is frequently species-specific in human and mouse.

Q Pan — 2005-11-18T09:12:35-00:00

Trends Genet, Vol. 21, No. 2. (February 2005), pp. 73-77.

In this article, we provide evidence that a frequent source of diversity between mammalian transcripts occurs as a consequence of species-specific alternative splicing (AS) of conserved exons. Using a highly predictive computational method, we estimate that >11% of human and mouse cassette alternative exons undergo skipping in one species but constitutively splicing in the other. These species-specific AS events are predicted to modify conserved domains in proteins more frequently than other classes of AS events. The results thus provide evidence that species-specific AS of conserved exons constitutes an additional potential source of complexity and species-specific differences between mammals.

Functional Programming with Bananas, Lenses, Envelopes and Barbed Wire

Erik Meijer — 2005-09-27T19:34:51-00:00

Vol. 523 (1991), pp. 124-144.

We develop a calculus for lazy functional programming based on recursion operators associated with data type definitions. For these operators we derive various algebraic laws that are useful in deriving and manipulating programs. We shall show that all example functions in Bird and Wadler's "Introduction to Functional Programming" can be expressed using these operators. 1 Introduction Among the many styles and methodologies for the construction of computer programs the Squiggol style in our...

Ecological consequences of genetic diversity

Hughes — 2008-05-08T08:04:02-00:00

Ecology Letters, Vol. 11, No. 6. (June 2008), pp. 609-623.

Clothing manipulation

Takeo Igarashi — 2008-08-04T08:28:07-00:00

(2002), pp. 91-100.

The design of a pretty-printing library

John Hughes — 2008-08-04T01:58:23-00:00

Advanced Functional Programming (1995), pp. 53-96.

In this chapter we have considered the design of combinator libraries. We saw how studying the algebraic properties of the combinators desired can both help to suggest natural choices of representation, and guide the implementation of the operators. We saw several examples — lists, monads, and a pretty-printing library. For this kind of program development we need a language with higher-order functions and lazy evaluation, for which equational reasoning is valid; in other words, Haskell is ideally suited.

Two approaches to the facilitation of grammar in children with language impairment: an experimental evaluation.

ME Fey — 2008-08-01T06:27:43-00:00

Journal of speech and hearing research, Vol. 36, No. 1. (February 1993), pp. 141-157.

Two approaches to grammar facilitation in preschool-age children with language impairment were evaluated. One approach was administered by a speech-language pathologist and the other was presented by the subjects' parents, who were trained by the speech-language pathologist. Both treatment packages ran for 4 1/2 months and made use of focused stimulation procedures and a cyclical goal-attack strategy. Subjects were 30 children between the ages of 3:8 and 5:10 (years:months) who had marked delays in grammatical development. Children who served in a delayed-treatment control group averaged no gains over their no-treatment period. In contrast, large treatment effects were observed for both treatment groups on three of four measures of grammatical expression. However, closer inspection of the data revealed that the effects for the clinician treatment were more consistent across treatment administrations than were those for the parent treatment. Although the specific contributions of the focused stimulation procedures and the cyclical goal attack strategy were not evaluated, the results support the viability of these components as parts of larger treatment packages. The results also support the participation of parents as primary intervention agents in grammar facilitation programs. When parents take such a large role in the intervention process, however, it is imperative that the children's progress be monitored carefully and that program adjustments be made whenever gains are smaller than expected.

Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeast.

AB Parsons — 2006-09-20T16:12:52-00:00

Cell, Vol. 126, No. 3. (11 August 2006), pp. 611-625.

Discovering target and off-target effects of specific compounds is critical to drug discovery and development. We generated a compendium of "chemical-genetic interaction" profiles by testing the collection of viable yeast haploid deletion mutants for hypersensitivity to 82 compounds and natural product extracts. To cluster compounds with a similar mode-of-action and to reveal insights into the cellular pathways and proteins affected, we applied both a hierarchical clustering and a factorgram method, which allows a gene or compound to be associated with more than one group. In particular, tamoxifen, a breast cancer therapeutic, was found to disrupt calcium homeostasis and phosphatidylserine (PS) was recognized as a target for papuamide B, a cytotoxic lipopeptide with anti-HIV activity. Further, the profile of crude extracts resembled that of its constituent purified natural product, enabling detailed classification of extract activity prior to purification. This compendium should serve as a valuable key for interpreting cellular effects of novel compounds with similar activities.

A non-homogeneous hidden Markov model for precipitation occurrence

James Hughes — 2008-07-31T22:09:16-00:00

Applied Statistics, Vol. 48 (1999), pp. 15-30.

A nonhomogeneous hidden Markov model is proposed for relating precipitation occurrences at multiple rain gauge stations to broad-scale atmospheric circulation patterns (the so-called "downscaling problem"). We model a 15 year sequence of winter data from 30 rain stations in southwestern Australia. The first 10 years of data are used for model development and the remaining 5 years are used for model evaluation. The fitted model accurately reproduces the observed rainfall statistics in the reserved data despite a shift in atmospheric circulation (and, consequently, rainfall) between the two periods. The fitted model also provides some useful insights into the processes driving rainfall in this region.

Looking for Darwin in all the wrong places: the misguided quest for positive selection at the nucleotide sequence level

AL Hughes — 2007-07-12T00:30:24-00:00

Heredity, Vol. aop, No. current.

The power-law distribution of gene family size is driven by the pseudogenisation rate's heterogeneity between gene families.

Timothy Hughes — 2008-04-08T05:26:54-00:00

Gene (10 March 2008)

Genome sequencing has shown that the number of homologous gene families of a given size declines rapidly with family size. A power-law has been shown to provide the best mathematical description of this relationship. However, it remains unclear what evolutionary forces drive this observation. We use models of gene duplication, pseudogenisation and accumulation of replacement substitutions, which have been validated and parameterised using genomic data, to build a model of homologous gene evolution. We use this model to simulate the evolution of the distribution of gene family size and show that the power-law distribution is driven by the pseudogenisation rate's heterogeneity across gene families and its correlation within families. Moreover, we show that gene duplication and pseudogenisation are necessary and sufficient for the emergence of the power-law.

Data quality of general practice electronic health records: the impact of a program of assessments, feedback, and training.

M Porcheret — 2008-07-29T12:25:24-00:00

Journal of the American Medical Informatics Association : JAMIA, Vol. 11, No. 1. (b 2004), pp. 78-86.

OBJECTIVE: The aim of this study was to investigate the impact of a program of repeated assessments, feedback, and training on the quality of coded clinical data in general practice. DESIGN: A prospective uncontrolled intervention study was conducted in a general practice research network. MEASUREMENTS: Percentage of recorded consultations with a coded problem title and percentage of patients receiving a specific drug (e.g., tamoxifen) who had the relevant morbidity code (e.g., breast cancer) were calculated. Annual period prevalence of 12 selected morbidities was compared with parallel data derived from the fourth National Study of Morbidity Statistics from General Practice (MSGP4). RESULTS: The first two measures showed variation between practices at baseline, but on repeat assessments all practices improved or maintained their levels of coding. The period prevalence figures also were variable, but over time rates increased to levels comparable with, or above, MSGP4 rates. Practices were able to provide time and resources for feedback and training sessions. CONCLUSION: A program of repeated assessments, feedback, and training appears to improve data quality in a range of practices. The program is likely to be generalizable to other practices but needs a trained support team to implement it that has implications for cost and resources.

Trends in sexually transmitted infections in general practice 1990-2000: population based study using data from the UK general practice research database

Jackie Cassell — 2008-07-29T12:05:51-00:00

BMJ, Vol. 332, No. 7537. (11 February 2006), pp. 332-334.

Objective To describe the contribution of primary care to the diagnosis and management of sexually transmitted infections in the United Kingdom, 1990-2000, in the context of increasing incidence of infections in genitourinary medicine clinics. Design Population based study. Setting UK primary care. Participants Patients registered in the UK general practice research database. Main outcome measures Incidence of diagnosed sexually transmitted infections in primary care and estimation of the proportion of major such infections diagnosed in primary care. Results An estimated 23.0% of chlamydia cases in women but only 5.3% in men were diagnosed and treated in primary care during 1998-2000, along with 49.2% cases of non-specific urethritis and urethral discharge in men and 5.7% cases of gonorrhoea in women and 2.9% in men. Rates of diagnosis in primary care rose substantially in the late 1990s. Conclusions A substantial and increasing number of sexually transmitted infections are diagnosed and treated in primary care in the United Kingdom, with sex ratios differing from those in genitourinary medicine clinics. Large numbers of men are treated in primary care for presumptive sexually transmitted infections. 10.1136/bmj.38726.404120.7C

The reflectivity spectra of some group VA transition metal dichalcogenides

AR Beal — 2008-07-28T15:42:16-00:00

Journal of Physics C: Solid State Physics, Vol. 8, No. 24. (1975), pp. 4236-4234.

Reflectivity spectra from the basal planes of crystals of 2H-NbSe2, 2H-TaSe2, 2H-TaS2 and 1T-TaS2 have been measured in the energy range 25 meV to 14 eV at room temperature and liquid nitrogen temperature. Using extrapolations of the experimental data to 0 eV and 30 eV, a Kramers-Kronig analysis of the data has been performed. The optical data so obtained has been discussed and interpreted in terms of the proposed band model for these materials.

ARTICLES: Deliberate Introductions of Species: Research Needs ? Benefits can be reaped, but risks are high

JJ Ewel — 2008-07-26T06:37:55-00:00

BioScience (August 1999), pp. 619-630.

A high-resolution atlas of nucleosome occupancy in Yeast

William Lee — 2007-10-01T04:57:32-00:00

Nature Genetics, Vol. 39, No. 10. (16 September 2007), pp. 1235-1244.

Body Mnemonics - Portable device interaction design concept

Jussi Ängeslevä — 2008-07-25T09:05:09-00:00

Body Mnemonics is an interface design concept for portable devices that uses the body space of the user as an interface. In this system, information can be stored and subsequently accessed by moving a device to different locations around one's body. The system is designed to ease cognitive load by relying on our proprioceptive sense and the use of the body image of the user as a mnemonic frame of reference. The hardware approach is to use motion sensing in the device itself. Two user studies...

A taxa-area relationship for bacteria

Claire Horner-Devine — 2004-12-08T23:22:58-00:00

Nature, Vol. 432, No. 7018. (09 December 2004), pp. 750-753.

The application of rarefaction techniques to molecular inventories of microbial diversity.

JB Hughes — 2006-03-17T19:58:43-00:00

Methods Enzymol, Vol. 397 (2005), pp. 292-308.

With the growing capacity to inventory microbial community diversity, the need for statistical methods to compare community inventories is also growing. Several approaches have been proposed for comparing the diversity of microbial communities: some adapted from traditional ecology and others designed specifically for molecular inventories of microbes. Rarefaction is one statistical method that is commonly applied in microbial studies, and this chapter discusses the procedure and its advantages and disadvantages. Rarefaction compares observed taxon richness at a standardized sampling effort using confidence intervals. Special emphasis is placed here on the need for precise, rather than unbiased, estimation methods in microbial ecology, but precision can be judged only with a very large sample or with multiple samples drawn from a single community. With low sample sizes, rarefaction curves also have the potential to lead to incorrect rankings of relative species richness, but this chapter discusses a new method with the potential to address this problem. Finally, this chapter shows how rarefaction can be applied to the comparison of the taxonomic similarity of microbial communities.

Counting the Uncountable: Statistical Approaches to Estimating Microbial Diversity

Jennifer Hughes — 2007-11-16T12:32:34-00:00

Appl. Environ. Microbiol., Vol. 67, No. 10. (1 October 2001), pp. 4399-4406.

10.1128/AEM.67.10.4399-4406.2001

Use of simultaneous pressure and velocity measurements to estimate arterial wave speed at a single site in humans

Justin Davies — 2008-07-24T14:20:40-00:00

Am J Physiol Heart Circ Physiol, Vol. 290, No. 2. (1 February 2006), pp. H878-885.

It has not been possible to measure wave speed in the human coronary artery, because the vessel is too short for the conventional two-point measurement technique used in the aorta. We present a new method derived from wave intensity analysis, which allows derivation of wave speed at a single point. We apply this method in the aorta and then use it to derive wave speed in the human coronary artery for the first time. We measured simultaneous pressure and Doppler velocity with intracoronary wires at the left main stem, left anterior descending and circumflex arteries, and aorta in 14 subjects after a normal coronary arteriogram. Then, in 10 subjects, serial measurements were made along the aorta before and after intracoronary isosorbide dinitrate. Wave speed was derived by two methods in the aorta: 1) the two-site distance/time method (foot-to-foot delay of pressure waveforms) and 2) a new single-point method using simultaneous pressure and velocity measurements. Coronary wave speed was derived by the single-point method. Wave speed derived by the two methods correlated well (r = 0.72, P < 0.05). Coronary wave speed correlated with aortic wave speed (r = 0.72, P = 0.002). After nitrate administration, coronary wave speed fell by 43%: from 16.4 m/s (95% confidence interval 12.6-20.1) to 9.3 m/s (95% confidence interval 6.5-12.0, P < 0.001). This single-point method allows determination of wave speed in the human coronary artery. Aortic wave speed is correlated to coronary wave speed. Finally, this technique detects the prompt fall in coronary artery wave speed with isosorbide dinitrate. 10.1152/ajpheart.00751.2005