Blogs as a Means of Preservation Selection for the World Wide Web

Currently, there is not a very strong system of selection in place when looking at the Web as a whole. This study is an examination of the blogging community for the possibility of utilizing the decentralized and distributed nature of link selection that takes place within the community as a means of preservation selection. The purpose of this study is to compare the blog aggregators, Daypop, Blogdex, and BlogPulse, for their ability to collect content which is of archival quality. This study analyzes the content selected by the aggregators to determine if any content which is linked most frequently for a given day is of archival quality. Archival quality is determined by comparing the content from the aggregator lists to criteria assembled for the study from a variety of archival policies and principles

Klotho and the treatment of human malignancies

Klotho was first discovered as an anti-ageing protein linked to a number of age-related disease processes, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions. Emerging research has also demonstrated a potential therapeutic role for Klotho in cancer biology, which is perhaps unsurprising given that cancer and ageing share similar molecular hallmarks. In addition to functioning as a tumour suppressor in numerous solid tumours and haematological malignancies, Klotho represents a candidate therapeutic target for patients with these diseases, the majority of whom have limited treatment options. Here, we examine contemporary evidence evaluating the anti-neoplastic effects of Klotho and describe the modulation of downstream oncogenic signalling pathways, including Wnt/β-catenin, FGF, IGF1, PIK3K/AKT, TGFβ, and the Unfolded Protein Response. We also discuss possible approaches to developing therapeutic Klotho and consider technological advances that may facilitate the delivery of Klotho through gene therapy

Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters

RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the SNAP complex (SNAPc). The main distinguishing feature is the presence, in the type 3 promoters only, of a TATA box, which determines Pol III specificity. To understand the mechanism by which the absence or presence of a TATA box results in specific Pol recruitment, we examined how SNAPc and general transcription factors required for Pol II or Pol III transcription of SNAPc-dependent genes (i.e., TATA-box-binding protein [TBP], TFIIB, and TFIIA for Pol II transcription and TBP and BRF2 for Pol III transcription) assemble to ensure specific Pol recruitment. TFIIB and BRF2 could each, in a mutually exclusive fashion, be recruited to SNAPc. In contrast, TBP-TFIIB and TBP-BRF2 complexes were not recruited unless a TATA box was present, which allowed selective and efficient recruitment of the TBP-BRF2 complex. Thus, TBP both prevented BRF2 recruitment to Pol II promoters and enhanced BRF2 recruitment to Pol III promoters. On Pol II promoters, TBP recruitment was separate from TFIIB recruitment and enhanced by TFIIA. Our results provide a model for specific Pol recruitment at SNAPc-dependent promoters

DNA origami-based single-molecule force spectroscopy elucidates RNA Polymerase III pre-initiation complex stability

The TATA-binding protein (TBP) and a transcription factor (TF) IIB-like factor are important constituents of all eukaryotic initiation complexes. The reason for the emergence and strict requirement of the additional initiation factor Bdp1 in the RNA polymerase (RNAP) III system, however, remained elusive. A poorly studied aspect in this context is the effect of DNA strain arising from DNA compaction and transcriptional activity on initiation complex formation. We made use of a DNA origami-based force clamp to follow the assembly of human initiation complexes in the RNAP II and RNAP III systems at the single-molecule level under piconewton forces. We demonstrate that TBP-DNA complexes are force-sensitive and TFIIB is sufficient to stabilise TBP on a strained promoter. In contrast, Bdp1 is the pivotal component that ensures stable anchoring of initiation factors, and thus the polymerase itself, in the RNAP III system. Thereby, we offer an explanation for the crucial role of Bdp1 for the high transcriptional output of RNAP II

Development of innovative fuelling systems for fusion energy science

The development of innovative fueling systems in support of magnetic fusion energy, particularly the International Thermonuclear Experimental Reactor (ITER), is described. The ITER fuelling system will use a combination of deuterium-tritium (D-T) gas puffing and pellet injection to achieve and maintain ignited plasmas. This combination will provide a flexible fuelling source with D-T pellets penetrating beyond the separatrix to sustain the ignited fusion plasma and with deuterium-rich gas fuelling the edge region to meet divertor requirements in a process called isotopic fuelling. More advanced systems with potential for deeper penetration, such as multistage pellet guns and compact toroid injection, are also described

Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation.

Initiation of gene transcription by RNA polymerase (Pol) III requires the activity of TFIIIB, a complex formed by Brf1 (or Brf2), TBP (TATA-binding protein), and Bdp1. TFIIIB is required for recruitment of Pol III and to promote the transition from a closed to an open Pol III pre-initiation complex, a process dependent on the activity of the Bdp1 subunit. Here, we present a crystal structure of a Brf2-TBP-Bdp1 complex bound to DNA at 2.7 Å resolution, integrated with single-molecule FRET analysis and in vitro biochemical assays. Our study provides a structural insight on how Bdp1 is assembled into TFIIIB complexes, reveals structural and functional similarities between Bdp1 and Pol II factors TFIIA and TFIIF, and unravels essential interactions with DNA and with the upstream factor SNAPc. Furthermore, our data support the idea of a concerted mechanism involving TFIIIB and RNA polymerase III subunits for the closed to open pre-initiation complex transition.Transcription initiation by RNA polymerase III requires TFIIIB, a complex formed by Brf1/Brf2, TBP and Bdp1. Here, the authors describe the crystal structure of a Brf2-TBP-Bdp1 complex bound to a DNA promoter and characterize the role of Bdp1 in TFIIIB assembly and pre-initiation complex formation

Measurement of the branching ratio of the decay Ξ0→Σ+μ−νˉμ\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}

From the 2002 data taking with a neutral kaon beam extracted from the CERN-SPS, the NA48/1 experiment observed 97 $\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$ candidates with a background contamination of $30.8 \pm 4.2$ events. From this sample, the BR($\Xi^{0}\rightarrow \Sigma^{+} \mu^{-} \bar{\nu}_{\mu}$) is measured to be $(2.17 \pm 0.32_{\mathrm{stat}}\pm 0.17_{\mathrm{syst}})\times10^{-6}$

Observation of the rare decay K_S -> pi^0mu^+mu^-

A search for the decay K_S -> pi^0mu^+mu^- has been made by the NA48/1 Collaboration at the CERN SPS accelerator. The data were collected during 2002 with a high-intensity K_S beam. Six events were found with a background expectation of 0.22^+0.18_-0.11 event. Using a vector matrix element and unit form factor, the measured branching ratio is B(K_S -> pi^0mu^+mu^-)=[2.9^+1.5_-1.2(stat)+/-0.2(syst)]x10^{-9}.Comment: 19 pages, 8 figures, 4 tables. To be published in Physics Letters

First observation and branching fraction and decay parameter measurements of the weak radiative decay Xi0 --> Lambda e+e-

The weak radiative decay Xi0 --> Lambda e+e- has been detected for the first time. We find 412 candidates in the signal region, with an estimated background of 15 +/- 5 events. We determine the branching fraction B(Xi0 --> Lambda e+e-) = [7.6 +/- 0.4(stat) +/- 0.4(syst) +/- 0.2(norm)] x 10^{-6}, consistent with an internal bremsstrahlung process, and the decay asymmetry parameter alpha_{XiLambdaee} = -0.8 +/- 0.2, consistent with that of Xi0 --> Lambda gamma. The charge conjugate reaction Xi0_bar --> Lambda_bar e+e- has also been observed.Comment: 20 pages, 5 figures, 4 tables; revised: 19 pages, 4 figures, 4 tables, after reviewers' comments: 1 figure removed, 1 figure corrected, minor editorial changes; to be published in Phys. Lett.

Comprehensive in silico functional specification of mouse retina transcripts

BACKGROUND: The retina is a well-defined portion of the central nervous system (CNS) that has been used as a model for CNS development and function studies. The full specification of transcripts in an individual tissue or cell type, like retina, can greatly aid the understanding of the control of cell differentiation and cell function. In this study, we have integrated computational bioinformatics and microarray experimental approaches to classify the tissue specificity and developmental distribution of mouse retina transcripts. RESULTS: We have classified a set of retina-specific genes using sequence-based screening integrated with computational and retina tissue-specific microarray approaches. 33,737 non-redundant sequences were identified as retina transcript clusters (RTCs) from more than 81,000 mouse retina ESTs. We estimate that about 19,000 to 20,000 genes might express in mouse retina from embryonic to adult stages. 39.1% of the RTCs are not covered by 60,770 RIKEN full-length cDNAs. Through comparison with 2 million mouse ESTs, spectra of neural, retinal, late-generated retinal, and photoreceptor -enriched RTCs have been generated. More than 70% of these RTCs have data from biological experiments confirming their tissue-specific expression pattern. The highest-grade retina-enriched pool covered almost all the known genes encoding proteins involved in photo-transduction. CONCLUSION: This study provides a comprehensive mouse retina transcript profile for further gene discovery in retina and suggests that tissue-specific transcripts contribute substantially to the whole transcriptome