In vitro selected peptides bind with thymidylate synthase mRNA and inhibit its translation

Thymidylate synthase (TS), an essential enzyme for catalyzing the biosynthesis of thymidylate, is a critical therapeutic target in cancer therapy. Recent studies have shown that TS functions as an RNA-binding protein by interacting with two different sequences on its own mRNA, thus, repressing translational efficiency. In this study, peptides binding TS RNA with high affinity were isolated using mRNA display from a large peptide library (>10(13) different sequences). The randomized library was subjected up to twelve rounds of in vitro selection and amplification. Comparing the amino acid composition of the selected peptides (12th round, R12) with those from the initial random library (round zero, R0), the basic and aromatic residues in the selected peptides were enriched significantly, suggesting that these peptide regions might be important in the peptide-TS mRNA interaction. Categorizing the amino acids at each random position based on their physicochemical properties and comparing the distributions with those of the initial random pool, an obvious basic charge characteristic was found at positions 1, 12, 17 and 18, suggesting that basic side chains participate in RNA binding. Secondary structure prediction showed that the selected peptides of R12 pool represented a helical propensity compared with R0 pool, and the regions were rich in basic residues. The electrophoretic gel mobility shift and in vitro translation assays showed that the peptides selected using mRNA display could bind TS RNA specifically and inhibit the translation of TS mRNA. Our results suggested that the identified peptides could be used as new TS inhibitors and developed to a novel class of anticancer agents.

Stable carbon isotope analyses show dominance of C3 grasses in the feed selected by small herbivores at the alpine meadow at the Tibetan Plateau

Muscle samples were collected from small herbivorous mammals (Ochotona curzoniae, Microtus oecnomus, Myospalax fontanierii and Lepus oiostolus) at the alpine meadow ecosystem at the Tibetan Plateau in order to address variability in stable carbon isotope composition. Stable carbon isotope values of muscles remain steady and show no significant variations (-25.72 to -27.04 parts per thousand) among the four small mammal species. Based on the mass balance theory of stable isotopes, it is proposed that small herbivorous mammals mainly (or totally) rely on C3 grasses as food supply, and there is few or no distribution of C4 grasses at the ecosystem. The results reflect our previous study on the isotope patterns of plant species. Thus, stable carbon isotope analysis of muscles provides a method to address dietary selection and dietary variability in herbivores. In addition, stable carbon isotopic analyses can be used to address changes in vegetation distributions in ecosystem and paleovegetaion and paleoclimate.

复杂应力环境下断续节理岩体真三轴实验研究及其工程应用

The great deal of joints and faults , existing in the rock mass , are the leading cause of discontinuous rock mass. Structural planes not only destroy the integrality of rock mass, but also lead nonlinearity、heterogeneity、anisotropy and failure mode on mechanical properties of rock mass. Therefore the selection of strength and deformation parameters was very difficult. In practical rock mass engineering, equivalent parameters of rock mass were selected by the method of expert experience and engineering analogy. Based on the fine description of discontinuous joints in the type Ⅳ and Ⅴ rock mass and geological survey datum in situ, models was obtained by generalizing the structure of rock mass by the method of statistical analysis. Model intensity and deformation test were carried out on the true triaxial apparatus. Intermediate principle stress effect, anisotropy and dimension effect of discontinuous rock mass were considered in the model test. 3-D correction to Hoek-Brown empirical criterion was done by analysed the test datum. Detailed works were listed as follows: (1) The factors influenced intensity and deformation of discontinuous joints rock mass were the value of 、continuity, density and included angle of joints and anisotropy of joint plane. True triaxial intensity and deformation tests were carried out by considering above factors. The influence rule was obtained and corresponding relation formulary was established； (2) Based on the true triaxial tests under different stress path and load modes, we obtain intensity and deformation rule of rock mass； (3) Based on a great deal of true triaxial tests and other test datum, correction to the Hoek-Brown empirical criterion was done in the chapter 4. The intermediate principle stress was considered in the corrected formulary. It indicated that the formulary was applicable under a certain condition. In addition, the yield plane form of corrected Hoek-Brown empirical criterion under principle stress space was described in the paper. And the question of corner of yield plane was discussed； (4) Based on the single discontinuity theory, the three-dimensional intensity formulary of discontinuous joint rock mass was established. Correction to the intensity formulary was done considering intermediate principle stress effect. We may obtain the conclusion that the intensity of the discontinuous joint rock mass was influenced on compositive factors. They were 、 、continuity、internal frictional angle and cohesiveness of joint plane and rock； (5) The results of the true triaxial model test was applied into parameters evaluation of dam foundation rock mass of JinPing hydropower station. For there were abundant ophicalcite in the dam foundation, the interval of intensity and formation parameters influenced on continuity were determined based on test datum. (6) Especial mould for prismatic jointing model was designed. True triaxial intensity and deformation tests by Basalt with prismatic jointing were carried out. The influence of intermediate principle stress, stress path, anisotropy effect and dimensional effect to intensity and deformation was discussed in the chapter 6. The work of (3)、(4)、(6) was significative supplement and innovation to current test and theory.

地质规律约束下的波阻抗反演

Impedance inversion is very important in seismic technology. It is based on seismic profile. Good inversion result is derived from high quality seismic profile, which is formed using high resolution imaging resolution. High-resolution process demands that signal/noise ratio is high. It is very important for seismic inversion to improve signal/noise ratio. the main idea is that the physical parameter (wave impedance), which describes the stratigraphy directly, is achieved from seismic data expressing structural style indirectly. The solution of impedance inversion technology, which is based on convolution model, is arbitrary. It is a good way to apply the priori information as the restricted condition in inversion. An updated impedance inversion technology is presented which overcome the flaw of traditional model and highlight the influence of structure. Considering impedance inversion restricted by sedimentary model, layer filling style and congruence relation, the impedance model is built. So the impedance inversion restricted by geological rule could be realized. there are some innovations in this dissertation: 1. The best migration aperture is achieved from the included angle of time surface of diffracted wave and reflected wave. Restricted by structural model, the dip of time surface of reflected wave and diffracted wave is given. 2. The conventional method of FXY forcasting noise is updated, and the signal/noise ratio is improved. 3. Considering the characteristic of probability distribution of seismic data and geological events fully, an object function is constructed using the theory of Bayes estimation as the criterion. The mathematics is used here to describe the content of practice theory. 4. Considering the influence of structure, the seismic profile is interpreted to build the model of structure. A series of structure model is built. So as the impedance model. The high frequency of inversion is controlled by the geological rule. 5. Conjugate gradient method is selected to improve resolving process for it fit the demands of geophysics, and the efficiency of algorithm is enhanced. As the geological information is used fully, the result of impedance inversion is reasonable and complex reservoir could be forecasted further perfectly.

高山峡谷地区大跨度桥梁岸坡稳定性分析、趋势预测及应用研究

In order to realize fast development of the national economy in a healthy way and coordinate progress with whole society, the country has implemented the strategy of development of the western region. An important action of finishing this strategic task is to accelerate the highway construction in the western region, join the western region and places along the coast, the river, the border with goods and materials, technology, and personnel interchanges, and then drive development of the local economy.The western region was influenced by the Himalaya Tectonization in Cenozoic, and the crust rose and became the plateau. In the course of rising, rivers cut down sharply to form a lot of high mountains and gorges.Because of topography and geomorphology, bridges in the traffic construction in the alpine gorge area are needed. Rivers have characteristics of large flow, fast velocity and high and steep river valley, so building a pier in the river is not only very difficult, but also making the cost increase. At the same time, the impact that the pier is corroded and the bridge base that is drawn to be empty by flow are apt to cause destruction of the pier. For those reasons, suspending bridge and cable-stay bridge are usually adopted with the single and large span. For the large span bridge, the pier foundation could receive ten thousand and more vertical strength, bending moment and near kiloton horizontal thrust.Because bank slope in the alpine gorge district is cut deeply and unsettled big, natural stability is worse under endogenic and exogenic force. When bank slope bears heavy vertical strength, bending moment and horizontal thrust facing the river, it will inevitably make the balance state of rock and soil mass change, bridge bank slope deform, and even destroyed. So the key problem at the time of the large span's bridge construction in the alpine gorge area is how to make it stable.So based on the spot investigation, the Engineering Geology Analysis Method is very important to grasp the bank slope stability. It can provide the bank slope stability macroscopic ally and qualitatively, and reference to the indoor calculation. The Engineering Geology Analysis Method is that by way of analyzing and investigating terms of bank slope instability, stability development trend, the ancient rock slide and devolution in the site, stability comprehensive evaluation primarily, current and future stability of bank slope is gotten, realizing the intention to serving the concrete engineering.After the Engineering Geology Analysis Method is applied to project instances of BeiPan River Bridge and BaLin River Bridge, results are accord with bank slope actual conditions, which proves sites are suited to building bridges from site stability.we often meet bank slope stability issues in the traffic construction in the alpine gorge areao Before the evaluation of the bank slope stability, the engineering geological condition is investigated first. After that, the next exploration target and geology measures are decided. So, the Engineering Geology Analysis Method that the investigation of the engineering geological condition is the main content is quite important in practice. The other evaluations of the bank slope stability are based on it. Because foundation receives very heavy load, for the big span's bridge in the alpine gorge area, a long pile of the large diameter (D^0.8m) is usually selected. In order to reflect rock mass's deformation properties under rock-socketed pile function, the author has used the FLAG30 software for rock and soil mass and done many numerical simulations. By them, the author launches the further investigation on deformation properties of bank slope under different slope angle, pile length, diameter, elastic modulus, load, bank slope's structure, etc. Some conclusion meaningful to the design and produce are obtained.

Spatial Reference Frames for Object Recognition: Tuning for Rotations in Depth

The inferior temporal cortex (IT) of monkeys is thought to play an essential role in visual object recognition. Inferotemporal neurons are known to respond to complex visual stimuli, including patterns like faces, hands, or other body parts. What is the role of such neurons in object recognition? The present study examines this question in combined psychophysical and electrophysiological experiments, in which monkeys learned to classify and recognize novel visual 3D objects. A population of neurons in IT were found to respond selectively to such objects that the monkeys had recently learned to recognize. A large majority of these cells discharged maximally for one view of the object, while their response fell off gradually as the object was rotated away from the neuron"s preferred view. Most neurons exhibited orientation-dependent responses also during view-plane rotations. Some neurons were found tuned around two views of the same object, while a very small number of cells responded in a view- invariant manner. For five different objects that were extensively used during the training of the animals, and for which behavioral performance became view-independent, multiple cells were found that were tuned around different views of the same object. No selective responses were ever encountered for views that the animal systematically failed to recognize. The results of our experiments suggest that neurons in this area can develop a complex receptive field organization as a consequence of extensive training in the discrimination and recognition of objects. Simple geometric features did not appear to account for the neurons" selective responses. These findings support the idea that a population of neurons -- each tuned to a different object aspect, and each showing a certain degree of invariance to image transformations -- may, as an assembly, encode complex 3D objects. In such a system, several neurons may be active for any given vantage point, with a single unit acting like a blurred template for a limited neighborhood of a single view.

Colorimetric and ratiometric fluorescence sensing of fluoride: Tuning selectivity in proton transfer

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Energy-dependent in-situ small-angle x-ray scattering study of nano-ceramics

R Winter, D Le Messurier, CM Martin; Cryst Rev 12 (2006) 3 Sponsorship: EPSRC, CCLRC, Pilkington

The Paston Women: Selected Letters

Watt, D. (Ed.). (2004). The Paston Women: Selected Letters. Library of Medieval Women. Rochester: D. S. Brewer. RAE2008

Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study

BACKGROUND: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. METHODS:We conducted a genome wide association study (Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models (Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate [greater than or equal to]80%, minor allele frequency [greater than or equal to]10%, Hardy-Weinberg test p [greater than or equal to] 0.001).RESULTS:In family-based association test (FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 (physical positions 73,091,610 and 73, 527,652) were associated with age at death (p-value < 10-5). The two sets of SNPs were in high linkage disequilibrium (minimum r2 = 0.58). The top 30 SNPs for generalized estimating equation (GEE) tests of association with age at death included rs10507486 (p = 0.0001) and rs4943794 (p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations (FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 (p = 0.00003) near FOXO3a and rs3751591 (p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. CONCLUSION: Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging.

Open Issues on TCP for Mobile Computing

We discuss the design principles of TCP within the context of heterogeneous wired/wireless networks and mobile networking. We identify three shortcomings in TCP's behavior: (i) the protocol's error detection mechanism, which does not distinguish different types of errors and thus does not suffice for heterogeneous wired/wireless environments, (ii) the error recovery, which is not responsive to the distinctive characteristics of wireless networks such as transient or burst errors due to handoffs and fading channels, and (iii) the protocol strategy, which does not control the tradeoff between performance measures such as goodput and energy consumption, and often entails a wasteful effort of retransmission and energy expenditure. We discuss a solution-framework based on selected research proposals and the associated evaluation criteria for the suggested modifications. We highlight an important angle that did not attract the required attention so far: the need for new performance metrics, appropriate for evaluating the impact of protocol strategies on battery-powered devices.

Antenna tuning for wearable wireless sensors

When miniaturized wireless sensors are placed on or close to the human body, they can experience a significant loss inperformance due to antenna detuning, resulting in degradationof wireless performance as well as decreased battery lifetime.Several antenna tuning technologies have been proposed formobile wireless devices but devices suitable for widespread integration have yet to emerge. This paper highlights the possible advantages of antenna tuning for wearable wireless sensors and presents the design and characterization of a prototype 433MHz tuner module.

Representations of Catholicism in selected works by Colm Tóibín

The aim of this thesis is to provide an original and extensive study of Colm Tóibín as the “secular revisionist who acknowledges Catholicism as an enduring element of Irish society” (Ryan, Ireland and Scotland 251). Tóibín is uniquely placed to interpret many aspects of Ireland in the latter half of the twentieth century and I will argue that intertwined with his revisionism of Irish history is a reimagining of Ireland and Catholicism in fictive terms. An extensive amount of material from Tóibín’s time as a journalist and travel writer will feature in my research because it validates my argument concerning his prolonged engagement with Catholicism. Similarly, a broad range of Tóibín’s prose will be studied because it affords opportunities for an exploration of a literary Catholic oeuvre in his fiction. Therefore, I am emphasizing that a crucial linkage of Catholicism is identifiable throughout Tóibín’s diverse canon of work. However, I will argue that divergences of attitude and mode can be found in how Tóibín depicts Catholicism in his journalism and fiction. My argument identifies Tóibín’s recurrent journalistic questioning of the Church’s teaching and leadership but I classify a benignity towards Catholicism in his travel writing and fiction. Overall, Tóibín’s fiction merits significant status in this thesis because of the representations of Catholicism in the work of a writer who has been short-listed three times for The Booker Prize.