CA\TG Sequence at the 5'end of Oligo(A)-tracts Strongly Modulates DNA Curvature

An analysis of the base pair doublet geometries in available crystal structures indicates that the often reported intrinsic curvature of DNA containing oligo-(d(A).d(T)) tracts may also depend on the nature of the flanking sequences. The presence of CA/TG doublet in particular at the 5' end of these tracts is expected to enhance their intrinsic bending property. To test this proposition, three oligonucleotides, d(GAAAAACCCCCC), d(CCCCCCAAAAAG), d(GAAAAATTTTTC), and their complementary sequences were synthesized to study the effect of various flanking sequences, at the 5' and 3' ends of the A-tracts, on the curvature of DNA in solution. An analysis of the polyacrylamide gel electrophoretic mobilities of these sequences under different conditions of salts and temperatures (below their melting points) clearly showed that the oligomer with CA/TG sequence in the center was always more retarded than the oligomer with AC/GT sequence, as well as the oligomer with AT/AT sequence. Hydroxyl radical probing of the sequences with AC/GT and CA/TG doublet junctions gives a similar cutting pattern in the A-tracts, which is quite different from that in the C-tracts, indicating that the oligo(A)-tracts have similar structures in the two oligomers. KMnO4 probing shows that the oligomer with a CA/TG doublet junction forms a kink that is responsible for its inherent curvature and unusual electrophoretic mobility. UV melting shows a reduced thermal stability of the duplex with CA/TG doublet junction, and circular dichroism (CD) studies indicate that a premelting transition occurs in the oligomer with CA/TG doublet step before global melting but not in the oligomer with AC/GT doublet step, which may correspond to thermally induced unbending of the oligomer. These observations indicate that the CA/TG doublet junction at the 5' end of the oligo(A)-tract has a crucial role in modulating the overall curvature in DNA.

CAITG sequence at the 5' end of Oligo(A)-tracts strongly modulates DNA curvature

An analysis of the base pair doublet geometries in available crystal structures indicates that the often reported intrinsic curvature of DNA containing oligo-(d(A).d(T)) tracts may also depend on the nature of the flanking sequences. The presence of CA/TG doublet in particular at the 5' end of these tracts is expected to enhance their intrinsic bending property. To test this proposition, three oligonucleotides, d(GAAAAACCCCCC), d(CCCCCCAAAAAG), d(GAAAAATTTTTC), and their complementary sequences were synthesized to study the effect of various flanking sequences, at the 5' and 3' ends of the A-tracts, on the curvature of DNA in solution. An analysis of the polyacrylamide gel electrophoretic mobilities of these sequences under different conditions of salts and temperatures (below their melting points) clearly showed that the oligomer with CA/TG sequence in the center was always more retarded than the oligomer with AC/GT sequence, as well as the oligomer with AT/AT sequence. Hydroxyl radical probing of the sequences with AC/GT and CA/TG doublet junctions gives a similar cutting pattern in the A-tracts, which is quite different from that in the C-tracts, indicating that the oligo(A)-tracts have similar structures in the two oligomers. KMnO4 probing shows that the oligomer with a CA/TG doublet junction forms a kink that is responsible for its inherent curvature and unusual electrophoretic mobility. UV melting shows a reduced thermal stability of the duplex with CA/TG doublet junction, and circular dichroism (CD) studies indicate that a premelting transition occurs in the oligomer with CA/TG doublet step before global melting but not in the oligomer with AC/GT doublet step, which may correspond to thermally induced unbending of the oligomer. These observations indicate that the CA/TG doublet junction at the 5' end of the oligo(A)-tract has a crucial role in modulating the overall curvature in DNA.

A Fast Linear Separability Test by Projection of Positive Points on Subspaces

A geometric and non parametric procedure for testing if two finite set of points are linearly separable is proposed. The Linear Separability Test is equivalent to a test that determines if a strictly positive point h > 0 exists in the range of a matrix A (related to the points in the two finite sets). The algorithm proposed in the paper iteratively checks if a strictly positive point exists in a subspace by projecting a strictly positive vector with equal co-ordinates (p), on the subspace. At the end of each iteration, the subspace is reduced to a lower dimensional subspace. The test is completed within r ≤ min(n, d + 1) steps, for both linearly separable and non separable problems (r is the rank of A, n is the number of points and d is the dimension of the space containing the points). The worst case time complexity of the algorithm is O(nr3) and space complexity of the algorithm is O(nd). A small review of some of the prominent algorithms and their time complexities is included. The worst case computational complexity of our algorithm is lower than the worst case computational complexity of Simplex, Perceptron, Support Vector Machine and Convex Hull Algorithms, if d

Additional crayfish survey of Checkley Brook, Hollywood End Brook and Black Brook (Goyt) 1999

This is the report on the Additonal Crayfish Survey of Checkley Brook, Hollywood End Brook and Black Brook from 1999 by the Environment agency. The aim of the 1999 survey was to obtain a more complete picture of the crayfish distribution in those areas. It contains sections on the sampling methodology which followed the sampling done in 1998, the results of the sampling indicating the species of crayfish occurring in the sampling areas and some discussion and conclusions for each area. The appendix I contains maps locating the sampling points and past records. The appendix II contains detailed information of the sampling points.

JUSTEIS (JISC Usage Surveys: Trends in Electronic Information Services) Strand A: survey of end users of all electronic information services (HE and FE), with Action research report. Final report 2002/2003 Cycle Four.

Urquhart, C. (editor for JUSTEIS team), Spink, S., Thomas, R., Yeoman, A., Durbin, J., Turner, J., Armstrong, A., Lonsdale, R. & Fenton, R. (2003). JUSTEIS (JISC Usage Surveys: Trends in Electronic Information Services) Strand A: survey of end users of all electronic information services (HE and FE), with Action research report. Final report 2002/2003 Cycle Four. Aberystwyth: Department of Information Studies, University of Wales Aberystwyth with Information Automation Ltd (CIQM). Sponsorship: JISC

Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats

Advanced glycation end products (AGEs), formed from the nonenzymatic glycation of proteins and lipids with reducing sugars, have been implicated in many diabetic complications; however, their role in diabetic retinopathy remains largely unknown. Recent studies suggest that the cellular actions of AGEs may be mediated by AGE-specific receptors (AGE-R). We have examined the immunolocalization of AGEs and AGE-R components R1 and R2 in the retinal vasculature at 2, 4, and 8 months after STZ-induced diabetes as well as in nondiabetic rats infused with AGE bovine serum albumin for 2 weeks. Using polyclonal or monoclonal anti-AGE antibodies and polyclonal antibodies to recombinant AGE-R1 and AGE-R2, immunoreactivity (IR) was examined in the complete retinal vascular tree after isolation by trypsin digestion. After 2, 4, and 8 months of diabetes, there was a gradual increase in AGE IR in basement membrane. At 8 months, pericytes, smooth muscle cells, and endothelial cells of the retinal vessels showed dense intracellular AGE IR. AGE epitopes stained most intensely within pericytes and smooth muscle cells but less in basement membrane of AGE-infused rats compared with the diabetic group. Retinas from normal or bovine-serum-albumin-infused rats were largely negative for AGE IR. AGE-R1 and -R2 co-localized strongly with AGEs of vascular endothelial cells, pericytes, and smooth muscle cells of either normal, diabetic, or AGE-infused rat retinas, and this distribution did not vary with each condition. The data indicate that AGEs accumulate as a function of diabetes duration first within the basement membrane and then intracellularly, co-localizing with cellular AGE-Rs. Significant AGE deposits appear within the pericytes after long-term diabetes or acute challenge with AGE infusion conditions associated with pericyte damage. Co-localization of AGEs and AGE-Rs in retinal cells points to possible interactions of pathogenic significance.

Surrogate-based analysis and optimization for the design of heat sinks with jet impingement

Heat sinks are widely used for cooling electronic devices and systems. Their thermal performance is usually determined by the material, shape, and size of the heat sink. With the assistance of computational fluid dynamics (CFD) and surrogate-based optimization, heat sinks can be designed and optimized to achieve a high level of performance. In this paper, the design and optimization of a plate-fin-type heat sink cooled by impingement jet is presented. The flow and thermal fields are simulated using the CFD simulation; the thermal resistance of the heat sink is then estimated. A Kriging surrogate model is developed to approximate the objective function (thermal resistance) as a function of design variables. Surrogate-based optimization is implemented by adaptively adding infill points based on an integrated strategy of the minimum value, the maximum mean square error approach, and the expected improvement approaches. The results show the influence of design variables on the thermal resistance and give the optimal heat sink with lowest thermal resistance for given jet impingement conditions. 

Sclera as a Surrogate Marker for Determining AGE-Modifications in Bruch's Membrane Using a Raman Spectroscopy-Based Index of Aging

PURPOSE. Raman spectroscopy is an effective probe of advanced glycation end products (AGEs) in Bruch's membrane. However, because it is the outermost layer of the retina, this extracellular matrix is difficult to analyze in vivo with current technology. The sclera shares many compositional characteristics with Bruch's membrane, but it is much easier to access for in vivo Raman analysis. This study investigated whether sclera could act as a surrogate tissue for Raman-based investigation of pathogenic AGEs in Bruch's membrane.

METHODS. Human sclera and Bruch's membrane were dissected from postmortem eyes (n = 67) across a wide age range (33-92 years) and were probed by Raman spectroscopy. The biochemical composition, AGEs, and their age-related trends were determined from data reduction of the Raman spectra and compared for the two tissues.

RESULTS. Raman microscopy demonstrated that Bruch's membrane and sclera are composed of a similar range of biomolecules but with distinct relative quantities, such as in the heme/collagen and the elastin/collagen ratios. Both tissues accumulated AGEs, and these correlated with chronological age (R(2) = 0.824 and R(2) = 0.717 for sclera and Bruch's membrane, respectively). The sclera accumulated AGE adducts at a lower rate than Bruch's membrane, and the models of overall age-related changes exhibited a lower rate (one-fourth that of Bruch's membrane) but a significant increase with age (P <0.05).

CONCLUSIONS. The results suggest that the sclera is a viable surrogate marker for estimating AGE accumulation in Bruch's membrane and for reliably predicting chronological age. These findings also suggest that sclera could be a useful target tissue for future patient-based, Raman spectroscopy studies. (Invest Ophthalmol Vis Sci 2011;52:1593-1598) DOI:10.1167/iovs.10-6554

Minimal residual disease detection in childhood acute lymphoblastic leukaemia patients at multiple time-points reveals high levels of concordance between molecular and immunophenotypic approaches

In this single centre study of childhood acute lymphoblastic leukaemia (ALL) patients treated on the Medical Research Council UKALL 97/99 protocols, it was determined that minimal residual disease (MRD) detected by real time quantitative polymerase chain reaction (RQ-PCR) and 3-colour flow cytometry (FC) displayed high levels of qualitative concordance when evaluated at multiple time-points during treatment (93.38%), and a combined use of both approaches allowed a multi time-point evaluation of MRD kinetics for 90% (53/59) of the initial cohort. At diagnosis, MRD markers with sensitivity of at least 0.01% were identified by RQ-PCR detection of fusion gene transcripts, IGH/TRG rearrangements, and FC. Using a combined RQ-PCR and FC approach, the evaluation of 367 follow-up BM samples revealed that the detection of MRD >1% at Day 15 (P = 0.04), >0.01% at the end of induction (P = 0.02), >0.01% at the end of consolidation (P = 0.01), >0.01% prior to the first delayed intensification (P = 0.01), and >0.1% prior to the second delayed intensification and continued maintenance (P = 0.001) were all associated with relapse and, based on early time-points (end of induction and consolidation) a significant log-rank trend (P = 0.0091) was noted between survival curves for patients stratified into high, intermediate and low-risk MRD groups.

A Scheme Design of Cloud + End Technology in Demand Side Management

Demand Side Management (DSM) plays an important role in Smart Grid. It has large scale access points, massive users, heterogeneous infrastructure and dispersive participants. Moreover, cloud computing which is a service model is characterized by resource on-demand, high reliability and large scale integration and so on and the game theory is a useful tool to the dynamic economic phenomena. In this study, a scheme design of cloud + end technology is proposed to solve technical and economic problems of the DSM. The architecture of cloud + end is designed to solve technical problems in the DSM. In particular, a construct model of cloud + end is presented to solve economic problems in the DSM based on game theories. The proposed method is tested on a DSM cloud + end public service system construction in a city of southern China. The results demonstrate the feasibility of these integrated solutions which can provide a reference for the popularization and application of the DSM in china.

Fast and accurate multi-scale keypoints based on end-stopped cells

Increasingly more applications in computer vision employ interest points. Algorithms like SIFT and SURF are all based on partial derivatives of images smoothed with Gaussian filter kemels. These algorithrns are fast and therefore very popular.

Students' choice of a master in management in Portugal: A means-end chain approach

In the increasingly competitive market of higher education introduced by the Bologna Declaration, understanding the decision-making of master in management students is at the center of institutional management and marketing efforts on its mission to attract prospective students in a less costly, more efficient manner. The means-end chain approach, applied to the choice of a Portuguese institution in which to pursue a master in management, points to the position in rankings and to the non-specificity of the program as the most important attributes. Additionally, results show that students with distinct demographic, household, or background characteristics choose in significantly different manners.

Alternative ways to estimate change points in multinomial sequences. An application to an authorship attribution problem

The statistical analysis of literary style is the part of stylometry that compares measurable characteristics in a text that are rarely controlled by the author, with those in other texts. When the goal is to settle authorship questions, these characteristics should relate to the author’s style and not to the genre, epoch or editor, and they should be such that their variation between authors is larger than the variation within comparable texts from the same author. For an overview of the literature on stylometry and some of the techniques involved, see for example Mosteller and Wallace (1964, 82), Herdan (1964), Morton (1978), Holmes (1985), Oakes (1998) or Lebart, Salem and Berry (1998). Tirant lo Blanc, a chivalry book, is the main work in catalan literature and it was hailed to be “the best book of its kind in the world” by Cervantes in Don Quixote. Considered by writters like Vargas Llosa or Damaso Alonso to be the first modern novel in Europe, it has been translated several times into Spanish, Italian and French, with modern English translations by Rosenthal (1996) and La Fontaine (1993). The main body of this book was written between 1460 and 1465, but it was not printed until 1490. There is an intense and long lasting debate around its authorship sprouting from its first edition, where its introduction states that the whole book is the work of Martorell (1413?-1468), while at the end it is stated that the last one fourth of the book is by Galba (?-1490), after the death of Martorell. Some of the authors that support the theory of single authorship are Riquer (1990), Chiner (1993) and Badia (1993), while some of those supporting the double authorship are Riquer (1947), Coromines (1956) and Ferrando (1995). For an overview of this debate, see Riquer (1990). Neither of the two candidate authors left any text comparable to the one under study, and therefore discriminant analysis can not be used to help classify chapters by author. By using sample texts encompassing about ten percent of the book, and looking at word length and at the use of 44 conjunctions, prepositions and articles, Ginebra and Cabos (1998) detect heterogeneities that might indicate the existence of two authors. By analyzing the diversity of the vocabulary, Riba and Ginebra (2000) estimates that stylistic boundary to be near chapter 383. Following the lead of the extensive literature, this paper looks into word length, the use of the most frequent words and into the use of vowels in each chapter of the book. Given that the features selected are categorical, that leads to three contingency tables of ordered rows and therefore to three sequences of multinomial observations. Section 2 explores these sequences graphically, observing a clear shift in their distribution. Section 3 describes the problem of the estimation of a suden change-point in those sequences, in the following sections we propose various ways to estimate change-points in multinomial sequences; the method in section 4 involves fitting models for polytomous data, the one in Section 5 fits gamma models onto the sequence of Chi-square distances between each row profiles and the average profile, the one in Section 6 fits models onto the sequence of values taken by the first component of the correspondence analysis as well as onto sequences of other summary measures like the average word length. In Section 7 we fit models onto the marginal binomial sequences to identify the features that distinguish the chapters before and after that boundary. Most methods rely heavily on the use of generalized linear models

The embracing end-to-side neurorrhaphy in rats

OBJETIVO: Comparar dois novos métodos com o método tradicional da neurorrafia término-lateral. MÉTODOS: Os ratos foram separados em quatro grupos. No grupo A-E o nervo peroneal foi seccionado e o coto distal foi suturado à lateral do nervo tibial com dois pontos de nylon 10-0. No grupo A-D duas abas de epi-perineuro abraçaram o nervo doador. No grupo B-D foi realizada sutura com um único ponto abraçando o nervo doador. O grupo B-E foi o controle. Após seis meses foram observados massa do músculo tibial cranial e morfometria do coto distal do nervo peroneal. RESULTADOS: Foi encontrada menor massa muscular nos grupos A-D, A-E e B-D quando comparados com o grupo B-E (p<0.0001) e mesma massa quando comparados entre si (p>0,05). Os grupos A-D, A-E e B-D apresentaram menor número de fibras nervosas quando comparados ao grupo B-E (p=0,0155; p=0,016; p=0,0021) e mesmo número quando comparados entre si. CONCLUSÃO: Os três tipos de neurorrafia não apresentaram diferenças relacionadas à massa muscular e número de fibras nervosas sugerindo que a sutura abraçante com apenas um ponto apresente grande potencial em áreas cirúrgicas mais profundas.

Coincidence points of fiber maps on S-n-bundles

In this note we study coincidence of pairs of fiber-preserving maps f, g : E-1 -> E-2 where E-1, E-2 are S-n-bundles over a space B. We will show that for each homotopy class vertical bar f vertical bar of fiber-preserving maps over B, there is only one homotopy class vertical bar g vertical bar such that the pair (f, g), where vertical bar g vertical bar = vertical bar tau circle f vertical bar can be deformed to a coincidence free pair. Here tau : E-2 -> E-2 is a fiber-preserving map which is fixed point free. In the case where the base is S-1 we classify the bundles, the homotopy classes of maps over S-1 and the pairs which can be deformed to coincidence free. At the end we discuss the self-coincidence problem. (C) 2010 Elsevier B.V. All rights reserved.