The NCBI now maintains the Short Read Archive (SRA) (www.ncbi.nlm.nih.gov/Traces/ sra/) as a repository for data from sequencing projects that use the new massively parallel sequencing technologies, often called next-generation sequencing. These methods can generate hundreds of megabases to gigabases of data in a single instrument run, millions of times the output of a standard Sanger sequencing instrument. Applications of these technologies include sequencing of new genomes, re-sequencing of targeted genomic regions, sequencing complete genomes of multiple individuals to mine for variations, transcriptome sequencing to sample splice variants and expression levels, environmental samples and other metagenome sequencing, and chromatin DNA binding protein analysis. SRA provides the ability to search and display aspects of SRA project data through the SRA homepage (Figure 1, top panel), and the Entrez system (Figure 1, bottom panel. The SRA site also provides direct access to download data through the Aspera Connect (www.aspera.com) client that offers much faster transfers than traditional ftp. A recently added BLAST service allows searches against the transcriptome sequencing studies from the SRA data.

The Basic Local Alignment Search Tool (BLAST) website at the National Center for Biotechnology (NCBI) is an important resource for searching and aligning sequences. A new BLAST report allows faster loading of alignments, adds navigation aids, allows easy downloading of subject sequences and reports and has improved usability. Here, we describe these improvements to the BLAST report, discuss design decisions, describe other improvements to the search page and database documentation and outline plans for future development. The NCBI BLAST URL is http://blast.ncbi.nlm.nih.gov.

The Selex experiment measured several billion charged hadron tracks with a high precision magnetic momentum spectrometer and high precision RICH velocity spectrometer. We have analysed these data to simultaneously measure the masses of all the long lived charged hadrons and anti-hadrons from the 71 to the Omega using the same detector and technique. The statistical precision achievable with this data sample is more than adequate for 0.1% mass measurements.We have used these measurements to develop and understand the systematic effects in using a RICH as a precision velocity spectrometer with the goal of measuring 10 masses with precision ranging from 100 KeV for the lightest to 1000 KeV for the heaviest. This requires controlling the radius measurement of RICH rings to the similar to 10(-4) level. Progress in the mass measurements and the required RICH analysis techniques developed are discussed. (C) 2010 Elsevier B.V. All rights reserved.

The National Center for Biotechnology Information (NCBI) hosts 39 literature and molecular biology databases containing almost half a billion records. As the complexity of these data and associated resources and tools continues to expand, so does the need for educational resources to help investigators, clinicians, information specialists and the general public make use of the wealth of public data available at the NCBI. This review describes the educational resources available at NCBI via the NCBI Education page (www.ncbi.nlm.nih.gov/Education/). These resources include materials designed for new users, such as About NCBI and the NCBI Guide, as well as documentation, Frequently Asked Questions (FAQs) and writings on the NCBI Bookshelf such as the NCBI Help Manual and the NCBI Handbook. NCBI also provides teaching materials such as tutorials, problem sets and educational tools such as the Amino Acid Explorer, PSSM Viewer and Ebot. NCBI also offers training programs including the Discovery Workshops, webinars and tutorials at conferences. To help users keep up-to-date, NCBI produces the online NCBI News and offers RSS feeds and mailing lists, along with a presence on Facebook, Twitter and YouTube.

A sensor detects certain types of search terms and provides access to potentially more relevant results. For PubMed, new sensors include a Citation Sensor that is activated when someone searches with a literature citation and an Accession Sensor that provides a direct link to the sequence databases when someone searches with an NCBI sequence identifier. A variable type of sensor, the Hot Topic Sensor, also appears in PubMed. This new sensor that was inspired by the rapidly changing state of data for H1N1 influenza virus during the current outbreak appears for searches relevant to the recently added H1N1 viral sequences but in the future will be tailored to respond to other topical issues. The new more precise Gene Sensor that debuted in the PubMed database in January is now available in the protein and nucleotide databases.

Data from the power output of the radioisotope thermoelectric generators aboard the Cassini spacecraft are used to test the conjecture that small deviations observed in terrestrial measurements of the exponential radioactive decay law are correlated with the Earth–Sun distance. No significant deviations from exponential decay are observed over a range of 0.7–1.6 A.U. A 90% CL upper limit of 0.84×10-4 is set on a term in the decay rate of 238Pu proportional to 1/R2 and 0.99×10-4 for a term proportional to 1/R. The terrestrially measured Earth–Sun distance correlation is ∼(3×10-2)/R2.

NCBI BioSystems is a new database that collects information on interacting sets of biomolecules involved in metabolic and signaling pathways, disease states, and other biological processes. BioSystems currently contains biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the EcoCyc (Escherichia coli K-12 MG1655) subset of the BioCyc databases and is designed to accommodate other data in the future. BioSystems is fully integrated with other databases in the Entrez system with links to related literature, genes, protein sequences, structures, chemical data, and to related BioSystems. Along with links to related data at the NCBI site, each BioSystem record provides links to detailed diagrams and annotations for individual pathways on the Web sites of the source databases. BioSystems adds an important new aspect to the NCBI system by linking many different kinds of molecular records in biochemical pathways and providing means to compare these pathways across organisms.

I will review recent results in charmed meson spectroscopy from the Fermilab fixed target charm photo-production and hadro-production experiments, FOCUS and SELEX. FOCUS reports new measurements of the masses and widths of the D2*+ and D2* mesons, evidence for D0*+ and D0* broad states and a confirming observation of the DsJ+(2317) and other recently observed high mass DsJ+ states. SELEX has recently reported evidence for a new DsJ+(2632) state in both the Ds+η0 and D0K+ final states.

We show that Sigma(+) hyperons produced by 800 GeV/c protons on targets of Be and Cu have significant polarizations (15-20%). These polarizations persist at values of p(t)approximate to2 GeV/c and a wide range of x(F). The polarizations from the Cu target are consistently less than from Be. The average ratio of the Sigma(+) polarization from Cu to that from Be is 0.68+/-0.08.

Analogues Dmt-Tic (2',6'-dimethyl-L-tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) pharmacophore, a potent delta-opioid receptor antagonist, inhibited hMDR1 P-GP expressed in a G-185 fibroblast cell line in a manner similar to verapamil. N,N(Me)2-Dmt-Tic-NH-1-adamantane, H-Dmt-Tic-NH-1-adamantane, H-Dmt-Tic-Ala-NH-1-adamantane and N,N(Me)2-Dmt-Tic-NH-tBut were highly effective inhibitors. Weaker inhibition was observed with N,N(Et)2-Dmt-Tic-OH, H-Dmt-Tic-Ala-NH-tert-butyl amide and cyclo(Dmt-Tic). Results demonstrate that N- and C-terminal hydrophobic/lipophilic analogues of the Dmt-Tic pharmacophore inhibit hMDR1 and point to a potential role as chemosensitizing agents in chemotherapy for cancers containing hMDR1.

This document is an abridgement of the commemorative book prepared on the occasion of the symposium "In Celebration of the Fixed Target Program with the Tevatron" held at Fermilab on June 2, 2000. The full text with graphics contains, in addition to the material here, a section for each experiment including a "plain text" description, lists of all physics publications, lists of all degree recipients and a photo from the archives. The full text is available on the web at: http://conferences.fnal.gov/tevft/book/

Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K(i) values with either [(3)H]DPDPE (delta(1) agonist) or [(3)H]N, N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH(2), -NHCH(3), -NH-1-adamantyl, -NH-tBu, -NH-5-tetrazolyl) had high delta affinities (K(i) = 0.16 to 1 nM) with variable mu affinities to yield nonselective or weakly mu-selective analogues. N, N-(Me)(2)Dmt-Tic-NH-1-adamantane exhibited dual delta and mu receptor affinities (K(i)delta = 0.16 nM and K(i)mu = 1.12 nM) and potent delta antagonism (pA(2) = 9.06) with mu agonism (IC(50) = 16 nM). H-Dmt-betaHTic-OH (methylene bridge between C(alpha) of Tic and carboxylate function) yielded a biostable peptide with high delta affinity (K(i) = 0.85 nM) and delta antagonism (pA(2) = 8.85) without mu bioactivity. Dmt-Tic-Ala-X (X = -NHCH(3), -OCH(3), -NH-1-adamantyl, -NHtBu) exhibited high delta affinities (K(i) = 0.06 to 0.2 nM) and elevated mu affinities (K(i) = 2.5 to 11 nM), but only H-Dmt-Tic-Ala-NH-1-adamantane and H-Dmt-Tic-Ala-NHtBu yielded delta receptor antagonism (pA(2) = 9.29 and 9.16, respectively). Thus, Dmt-Tic with hydrophobic C-terminal substituents enhanced mu affinity to provide delta antagonists with dual receptor affinities and bifunctional activity.

The deltorphins are a class of highly selective delta-opioid heptapeptides from the skin of the Amazonian frogs Phyllomedusa sauvagei and P. bicolor. The first of these fascinating peptides came to light in 1987 by cloning of the cDNA of from frog skins, while the other members of this family were identified either by cDNA or isolation of the peptides. The distinctive feature of deltorphins is the presence of a naturally occurring D-enantiomer at the second position in their common N-terminal sequence, Tyr-D-Xaa-Phe, comparable to dermorphin, which is the prototype of a group of mu-selective opioids from the same source. The D-amino acid and the anionic residues, either Glu or Asp, as well as their unique amino acid compositions are responsible for the remarkable biostability, high delta-receptor affinity, bioactivity and peptide conformation. This review summarizes a decade of research from many laboratories that defined which residues and substituents in the deltorphins interact with the delta-receptor and characterized pharmacological and physiological activities in vitro and in vivo. It begins with a historical description of the topic and presents general schema for the synthesis of peptide analogues of deltorphins A, B and C as a means to document the methods employed in producing a myriad of analogues. Structure activity studies of the peptides and their pharmacological activities in vitro are detailed in abundantly tabulated data. A brief compendium of the current level of knowledge of the delta-receptor assists the reader to appreciate the rationale for the design of these analogues. Discussion of the conformation of these peptides addresses how structure leads to further hypotheses regarding ligand receptor interaction. The review ends with a broad discussion of the potential applications of these peptides in clinical and therapeutic settings.

The deltorphins are a class of highly selective δ-opioid heptapeptides from the skin of the Amazonian frogs Phyllomedusa sauvagei and P. bicolor. The first of these fascinating peptides came to light in 1987 by cloning of the cDNA of from frog skins, while the other members of this family were identified either by cDNA or isolation of the peptides. The distinctive feature of deltorphins is the presence of a naturally occurring d-enantiomer at the second position in their common N-terminal sequence, Tyr–d-Xaa–Phe, comparable to dermorphin, which is the prototype of a group of μ-selective opioids from the same source. The d-amino acid and the anionic residues, either Glu or Asp, as well as their unique amino acid compositions are responsible for the remarkable biostability, high δ-receptor affinity, bioactivity and peptide conformation. This review summarizes a decade of research from many laboratories that defined which residues and substituents in the deltorphins interact with the δ-receptor and characterized pharmacological and physiological activities in vitro and in vivo. It begins with a historical description of the topic and presents general schema for the synthesis of peptide analogues of deltorphins A, B and C as a means to document the methods employed in producing a myriad of analogues. Structure–activity studies of the peptides and their pharmacological activities in vitro are detailed in abundantly tabulated data. A brief compendium of the current level of knowledge of the δ-receptor assists the reader to appreciate the rationale for the design of these analogues. Discussion of the conformation of these peptides addresses how structure leads to further hypotheses regarding ligand–receptor interaction. The review ends with a broad discussion of the potential applications of these peptides in clinical and therapeutic settings.

Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K-i values with either [H-3]DPDPE (delta(1) agonist) or [H-3]N,N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH2, -NHCH3, -NH-1-adamantyl, -NH-tBu, -NH-5-tetrazolyl) had high delta affinities (K-i = 0.16 to 1 nM) with variable mu affinities to yield nonselective or weakly mu-selective analogues, N,N-(Me)(2)Dmt-Tic-NH-1-adamantane exhibited dual delta and mu receptor affinities (K(i)delta = 0.16 nM and K(i)mu =1.12 nM) and potent delta antagonism (pA(2) = 9.06) with mu agonism (IC50 = 16 nM). H-Dmt-beta HTic-OH (methylene bridge between C-alpha of Tic and carboxylate function) yielded a biostable peptide with high delta affinity (K-i = 0.85 nM) and delta antagonism (pA(2) = 8.85) without mu bioactivity, Dmt-Tic-Ala-X (X = -NHCH3, -OCH3, -NH-1-adamantyl, -NHtBu) exhibited high delta affinities (K-i = 0.06 to 0.2 nM) and elevated mu affinities (K-i = 2.5 to 11 nM), but only -Dmt-Tic-Ala-NH-1-adamantane and H-Dmt-Tic-Ala-NHtBu yielded delta receptor antagonism (pA(2) = 9.29 and 9.16, respectively). Thus, Dmt-Tic with hydrophobic C-terminal substituents enhanced mu affinity to provide delta antagonists with dual receptor affinities and bifunctional activity.

The need for δ-receptor-selective opioid antagonists has led to their development based on structure–activity relationships of δ- and μ-opioid agonists. The unusual amino acid 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), found in a series of H-Tyr-Tic-Phe-(Phe)-OH peptides, is an essential feature of derivatives discussed in this article. Elimination of Phe yields the H-Tyr-Tic-OH dipeptide antagonists, while substitution of Tyr by 2′,6′-dimethyl-l-tyrosine (Dmt) gives H-Dmt-Tic-OH and numerous potent, high-affinity and ultraselective δ-opioid antagonists. This article reviews the emergence of derivatives based on the Tyr-Tic and Dmt-Tic pharmacophores as lead structures, and discusses potential clinical and therapeutic applications.