Generic Technique to Generate Large Branched DNA Complexes

The inherent self-recognition properties of DNA have led to its use as a scaffold for various nanotechnology self-assembly applications, with macromolecular complexes, metallic and semiconducting nanoparticles, proteins, inter alia, being assembled onto a designed DNA scaffold. Such structures may typically comprise a number of DNA molecules organized into macromolecules. Many studies have used synthetic methods to produce the constituent DNA molecules, but this typically constrains the molecules to be no longer than around 100 base pairs (30 nm). However, applications that require larger self-assembling DNA complexes, several tens of nanometers or more, need to be generated by other techniques. Here, we present a generic technique to generate large linear, branched, and/or circular DNA macromolecular complexes. The effectiveness of this technique is demonstrated here by the use of Lambda Bacteriophage DNA as a template to generate single- and double-branched DNA structures approximately 120 nm in size.

A framework of issues in large process modeling projects

As process management projects have increased in size due to globalised and company-wide initiatives, a corresponding growth in the size of process modeling projects can be observed. Despite advances in languages, tools and methodologies, several aspects of these projects have been largely ignored by the academic community. This paper makes a first contribution to a potential research agenda in this field by defining the characteristics of large-scale process modeling projects and proposing a framework of related issues. These issues are derived from a semi -structured interview and six focus groups conducted in Australia, Germany and the USA with enterprise and modeling software vendors and customers. The focus groups confirm the existence of unresolved problems in business process modeling projects. The outcomes provide a research agenda which directs researchers into further studies in global process management, process model decomposition and the overall governance of process modeling projects. It is expected that this research agenda will provide guidance to researchers and practitioners by focusing on areas of high theoretical and practical relevance.

An exploration of the effect of super large n-tuples on single layer RAMnets

N-tuple recognition systems (RAMnets) are normally modeled using a small number of input lines to each RAM, because the address space grows exponentially with the number of inputs. It is impossible to implement an arbitrarily-large address space as physical memory. But given modest amounts of training data, correspondingly modest numbers of bits will be set in that memory. Hash arrays can therefore be used instead of a direct implementation of the required address space. This paper describes some exploratory experiments using the hash array technique to investigate the performance of RAMnets with very large numbers of input lines. An argument is presented which concludes that performance should peak at a relatively small n-tuple size, but the experiments carried out so far contradict this. Further experiments are needed to confirm this unexpected result.

Finite-size effects and error-free communication in Gaussian channels

The efficacy of a specially constructed Gallager-type error-correcting code to communication in a Gaussian channel is examined. The construction is based on the introduction of complex matrices, used in both encoding and decoding, which comprise sub-matrices of cascading connection values. The finite-size effects are estimated for comparing the results with the bounds set by Shannon. The critical noise level achieved for certain code rates and infinitely large systems nearly saturates the bounds set by Shannon even when the connectivity used is low.

Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines

The formulation of plasmid DNA (pDNA) in cationic liposomes is a promising strategy to improve the potency of DNA vaccines. In this respect, physicochemical parameters such as liposome size may be important for their efficacy. The aim of the current study was to investigate the effect of vesicle size on the in vivo performance of liposomal pDNA vaccines after subcutaneous vaccination in mice. The tissue distribution of cationic liposomes of two sizes, 500 nm (PDI 0.6) and 140 nm (PDI 0.15), composed of egg PC, DOPE and DOTAP, with encapsulated OVA-encoding pDNA, was studied by using dual radiolabeled pDNA-liposomes. Their potency to elicit cellular and humoral immune responses was investigated upon application in a homologous and heterologous vaccination schedule with 3 week intervals. It was shown that encapsulation of pDNA into cationic lipsomes resulted in deposition at the site of injection, and strongest retention was observed at large vesicle size. The vaccination studies demonstrated a more robust induction of OVA-specific, functional CD8+ T-cells and higher antibody levels upon vaccination with small monodisperse pDNA-liposomes, as compared to large heterodisperse liposomes or naked pDNA. The introduction of a PEG-coating on the small cationic liposomes resulted in enhanced lymphatic drainage, but immune responses were not improved when compared to non-PEGylated liposomes. In conclusion, it was shown that the physicochemical properties of the liposomes are of crucial importance for their performance as pDNA vaccine carrier, and cationic charge and small size are favorable properties for subcutaneous DNA vaccination.

Exchange rate exposure : do size and foreign operations matter?

Purpose – The purpose of this paper is to examine the effect of firm size and foreign operations on the exchange rate exposure of UK non-financial companies from January 1981 to December 2001. Design/methodology/approach – The impact of the unexpected changes in exchange rates on firms’ stock returns is examined. In addition, the movements in bilateral, equally weighted (EQW) and trade-weighted and exchange rate indices are considered. The sample is classified according to firm size and the extent of firms’ foreign operations. In addition, structural changes on the relationship between exchange rate changes and individual firms’ stock returns are examined over three sub-periods: before joining the exchange rate mechanism (pre-ERM), during joining the ERM (in-ERM), and after departure from the ERM (post-ERM). Findings – The findings indicate that a higher percentage of UK firms are exposed to contemporaneous exchange rate changes than those reported in previous studies. UK firms’ stock returns are more affected by changes in the EQW, and US$ European currency unit exchange rate, and respond less significantly to the basket of 20 countries’ currencies relative to the UK pound exchange rate. It is found that exchange rate exposure has a more significant impact on stock returns of the large firms compared with the small and medium-sized companies. The evidence is consistent across all specifications using different exchange rate. The results provide evidence that the proportion of significant foreign exchange rate exposure is higher for firms which generate a higher percentage of revenues from abroad. The sensitivities of firms’ stock returns to exchange rate fluctuations are most evident in the pre-ERM and post-ERM periods. Practical implications – This study provides important implications for public policymakers, financial managers and investors on how common stock returns of various sectors react to exchange rate fluctuations. Originality/value – The empirical evidence supports the view that UK firms’ stock returns are affected by foreign exchange rate exposure.

Stock index reaction to large price changes:evidence frommajor Asian stock indexes

We examine the short-term price behavior of ten Asian stock market indexes following large price changes or “shocks”. Under the standard OLS regression, there is stronger support for return continuations particularly following positive and negative price shocks of less than 10% in absolute size. The results under the GJR-GARCH method provide stronger support for market efficiency, especially for large price shocks. For example, for the Hong Kong stock index, negative shocks of less than -5% but more than -10% generate a significant one day cumulative abnormal return (CAR) of-0.754% under the OLS method, but an insignificant CAR of 0.022% under the GJR-GARCH. We find no support for the uncertainty information hypothesis. Furthermore, the CARs following the period after the Asian financial crisis adjust more quickly to price shocks.

It's what you do and the way that you do it:team task, team size, and innovation-related group processes

This article describes a study of the relationships between team inputs (task type and team size) and team processes in 87 cross industry Portuguese teams, some of which had high and some low requirements to innovate. Team processes were measured using the Team Climate Inventory (TCI), which focuses on clarity of and commitment to team objectives, levels of participation, support for innovation, and quality emphases. Three hypotheses were tested. The first proposed that teams carrying out tasks with a high innovation requirement would have high scores on a measure of team processes. This was supported insofar as such teams reported higher levels of participation and support for innovation. The second hypothesis proposed that large teams would have poorer team processes. This hypothesis was confirmed. The third hypothesis concerned the interaction between size and innovation. The results suggested that large teams operating under a relatively high pressure to innovate have poorer team processes than large teams that do not have a high requirement to innovate.

Typical kernel size and number of sparse random matrices over Galois fields: a statistical physics approach

Using methods of statistical physics, we study the average number and kernel size of general sparse random matrices over GF(q), with a given connectivity profile, in the thermodynamical limit of large matrices. We introduce a mapping of GF(q) matrices onto spin systems using the representation of the cyclic group of order q as the q-th complex roots of unity. This representation facilitates the derivation of the average kernel size of random matrices using the replica approach, under the replica symmetric ansatz, resulting in saddle point equations for general connectivity distributions. Numerical solutions are then obtained for particular cases by population dynamics. Similar techniques also allow us to obtain an expression for the exact and average number of random matrices for any general connectivity profile. We present numerical results for particular distributions.

Influence of check and field size on the visual evoked magnetic response to a pattern shift stimulus

A decrease in the check size of a pattern shift stimulus increases the latency and amplitude of the visual evoked potential (VEP) P100. In addition, for a given check size, decreasing the size of the stimulus field increases the latency and amplitude of the P100. These results imply that the central regions of the retina make a significant contribution to the generation of the electrical P100. However, the corresponding magnetic P100m may have a different origin. We have studied the effects of check and field size on the P100m in five normal subjects using a DC-Squid, second-order gradiometer. Magnetic responses were recorded at the positive maximum of the P100m over the occipital scalp to six check sizes (10-100') presented in a large (13 degrees 34') and small (5 degrees 14') field and to a large check (100') presented in seven field sizes (1 degree 45' - 15 degrees 10'). No responses were recorded to any check size with a small field. Decreasing the check size presented in a large field increased latency of the P100m by approx. 30 ms while the amplitude of the response decreased with the largest reduction occurring between 70' and 12' checks. Using a large check, latency increased and amplitude decreased as the field size was reduced. The latency changes in response to check and field size were similar to those described for the VEP although the magnitudes of the magnetic changes were greater. Unlike the VEP, amplitude responses were maximal when large checks were presented in a large stimulus field. This suggests that regions outside the central retina make a more significant contribution to the visual evoked magnetic response than they do to the VEP, and that the P100m may be useful clinically in the study of diseases that affect the more peripheral regions of the retina.

Alzheimer's disease: size class frequency distribution of senile plaques: do they indicate when a brain tissue was affected?

The size class frequency distribution of a sample of senile plaques (SP) was determined in a total of 20 brain regions from 5 elderly cases of Alzheimer's disease (AD). The purpose of the study was to determine whether a comparison of the frequency distributions could be used to determine the chronology of SP development in the AD brain. SP from 10 microns to a maximum diameter of 160 microns were present in the tissue and the size class frequency distributions were positively skewed. The frequency distributions varied between brain regions in: (1) the size class containing the mode, (2) the degree of positive skew, and (3) the ratio of large to small SP. In most patients the ratio of large to small SP was higher in the hippocampus or adjacent gyrus compared with temporal, parietal and frontal neocortex. If the diameter of a SP reflects its age in the tissue than the data suggest that SP formed earlier either in the hippocampus or adjacent gyrus compared with the other neocortical tissues. However, this conclusion rests on a number of assumptions including: (1) that SP diameter is directly related to age, (2) that SP development occurs at similar rates in different brain regions and (3) that, once formed, SP are not removed from the tissue by astrocytes.

Size frequency distribution of senile plaques in post-mortem brains of five patients with senile dementia of the Alzheimer type (SDAT)

Numerous senile plaques are one of the most characteristic histological findings in SDAT brains. Large classical plaques may develop from smaller uncored forms. There is no strong evidence that, once formed, plaques disappear from the tissue. We have examined cresyl-violet stained sections of the parahippocampal gyrus (PHG), hippocampus, frontal lobe and temporal lobe of five SDAT patients. The frequency of various sizes of plaques were determined in each of these brain regions. Statistical analysis showed that the ratio of large plaques to small plaques was greater in the hippocampal formation (especially the PHG) than in the neocortex. One explanation of these results is that plaques grow more rapidly in the hippocampal formation than elsewhere. Alternatively, if the rate of plaque growth is much the same in different brain regions, the data suggest that plaques develop first in the hippocampal formation (especially the PHG) and only later spread to the neocortex. This interpretation is also consistent with the theory that the neuropathology of SDAT spreads from the olfactory cortex via the hippocampal formation to the neocortex. Further development of this technique may help identify the site of the primary lesion in SDAT.

Large diameter optic nerve axon fibres in Alzheimer's disease

A variety of visual symptoms have been associated with Alzheimer's disease (AD). These include delays in flash visual evoked potentials which indicate a disruption of the integrity of the visual pathway. Examination of the visual cortex has revealed the presence of both senile plaques and neurofibrillary tangles. The purpose of this study was to determine whether there were differences in the number and/or size of optic nerve axons between AD patients and non-demented age-matched controls. Five optic nerves from AD patients and five from age-matched controls were embedded in epon resin and 1 micron sections prepared on a Reichert ultramicrotome. The sections were then stained in toluidine blue and examined at x400 magnification. The numbers of axons were counted in photographs of three fields taken at random from each section. To evaluate the axon diameters, 70 axons were chosen at random from each patient and measured using a calibrated eyepiece graticule. The total axon counts revealed no significant differences between the AD optic nerves and the age-matched controls. However, the frequency distribution of axon diameters was significantly different in the two groups. In particular, there were fewer larger diameter axons in patients with AD as previously reported. Degeneration of the large diameter axons suggests involvement of the magnocellular as opposed to the parvocellular pathways. Hence, there could be differences in visual performance of AD patients compared with normals which could be important in clinical diagnosis.

Sequential, Bayesian geostatistics:a principled method for large data sets

The principled statistical application of Gaussian random field models used in geostatistics has historically been limited to data sets of a small size. This limitation is imposed by the requirement to store and invert the covariance matrix of all the samples to obtain a predictive distribution at unsampled locations, or to use likelihood-based covariance estimation. Various ad hoc approaches to solve this problem have been adopted, such as selecting a neighborhood region and/or a small number of observations to use in the kriging process, but these have no sound theoretical basis and it is unclear what information is being lost. In this article, we present a Bayesian method for estimating the posterior mean and covariance structures of a Gaussian random field using a sequential estimation algorithm. By imposing sparsity in a well-defined framework, the algorithm retains a subset of “basis vectors” that best represent the “true” posterior Gaussian random field model in the relative entropy sense. This allows a principled treatment of Gaussian random field models on very large data sets. The method is particularly appropriate when the Gaussian random field model is regarded as a latent variable model, which may be nonlinearly related to the observations. We show the application of the sequential, sparse Bayesian estimation in Gaussian random field models and discuss its merits and drawbacks.

Variable impedance bearings for large rotating machinery

This thesis describes an investigation which was carried out under the Interdisciplinary Higher Degres (IHD) Scheme of The University of Aston in Birmingham. The investigation, which involved joint collaboration between the IHD scheme, the Department of Mechanical Engineering, and G.E.C. Turbine Generators Limited, was concerned with hydrostatic bearing characteristics and of how hydrostatic bearings could be used to enable turbine generator rotor support impedances to be controlled to give an improved rotor dynamic response. Turbine generator rotor critical speeds are determined not only by the mass and flexibility of the rotor itself, which are relatively easily predicted, but also by the dynamic characteristics of the bearing oil film, pedestal, and foundations. It is because of the difficulty in accurately predicting the rotor support characteristics that the designer has a problem in ensuring that a rotor's normal running speed is not close to one of its critical speeds. The consequence of this situation is that some rotors do have critical speeds close to their normal running speed and the resulting high levels of vibration cause noise, high rotor stresses, and a shortening of bearing life. A combined theoretical and experimental investigation of the effects of mounting the normal rotor journal bearing in a hydrostatic bearing was carried out. The purpose of the work was to show that by changing the oil flow resistance offered by capillaries connecting accumulators to the hydrostatic bearing, the overall rotor support characteristics could be tuned to enable rotor critical speeds to be moved at will. Testing of a combined journal and hydrostatic bearing has confirmed the theory of its operation and a theoretical study of a full size machine showed that its critical speed could be moved by over 350 rpm and that its rotor vibration at running speed could be reduced by 80%.